Viruses

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Open AccessReview

Latency, Integration, and Reactivation of Human Herpesvirus-6

by Shara N. Pantry and Peter G. Medveczky

Viruses 2017, 9(7), 194; https://doi.org/10.3390/v9070194 - 24 Jul 2017

Cited by 80 | Viewed by 10403

Human herpesvirus-6A (HHV-6A) and human herpesvirus-6B (HHV-6B) are two closely related viruses that infect T-cells. Both HHV-6A and HHV-6B possess telomere-like repeats at the terminal regions of their genomes that facilitate latency by integration into the host telomeres, rather than by episome formation. [...] Read more.

Human herpesvirus-6A (HHV-6A) and human herpesvirus-6B (HHV-6B) are two closely related viruses that infect T-cells. Both HHV-6A and HHV-6B possess telomere-like repeats at the terminal regions of their genomes that facilitate latency by integration into the host telomeres, rather than by episome formation. In about 1% of the human population, human herpes virus-6 (HHV-6) integration into germline cells allows the viral genome to be passed down from one generation to the other; this condition is called inherited chromosomally integrated HHV-6 (iciHHV-6). This review will cover the history of HHV-6 and recent works that define the biological differences between HHV-6A and HHV-6B. Additionally, HHV-6 integration and inheritance, the capacity for reactivation and superinfection of iciHHV-6 individuals with a second strain of HHV-6, and the role of hypomethylation of human chromosomes during integration are discussed. Overall, the data suggest that integration of HHV-6 in telomeres represent a unique mechanism of viral latency and offers a novel tool to study not only HHV-6 pathogenesis, but also telomere biology. Paradoxically, the integrated viral genome is often defective especially as seen in iciHHV-6 harboring individuals. Finally, gaps in the field of HHV-6 research are presented and future studies are proposed. Full article

(This article belongs to the Special Issue Viruses and Telomeres)

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Open AccessReview

Applicability of Metal Nanoparticles in the Detection and Monitoring of Hepatitis B Virus Infection

by Maxim Shevtsov, Lili Zhao, Ulrike Protzer and Maarten A. A. van de Klundert

Viruses 2017, 9(7), 193; https://doi.org/10.3390/v9070193 - 21 Jul 2017

Cited by 27 | Viewed by 7547

Abstract

Chronic infection with the hepatitis B virus (HBV) can lead to liver failure and can cause liver cirrhosis and hepatocellular carcinoma (HCC). Reliable means for detecting and monitoring HBV infection are essential to identify patients in need of therapy and to prevent HBV [...] Read more.

Chronic infection with the hepatitis B virus (HBV) can lead to liver failure and can cause liver cirrhosis and hepatocellular carcinoma (HCC). Reliable means for detecting and monitoring HBV infection are essential to identify patients in need of therapy and to prevent HBV transmission. Nanomaterials with defined electrical, optical, and mechanical properties have been developed to detect and quantify viral antigens. In this review, we discuss the challenges in applying nanoparticles to HBV antigen detection and in realizing the bio-analytical potential of such nanoparticles. We discuss recent developments in generating detection platforms based on gold and iron oxide nanoparticles. Such platforms increase biological material detection efficiency by the targeted capture and concentration of HBV antigens, but the unique properties of nanoparticles can also be exploited for direct, sensitive, and specific antigen detection. We discuss several studies that show that nanomaterial-based platforms enable ultrasensitive HBV antigen detection. Full article

(This article belongs to the Special Issue Recent Advances in Hepatitis B Virus Research)

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Open AccessReview

Drosophila: Retrotransposons Making up Telomeres

by Elena Casacuberta

Viruses 2017, 9(7), 192; https://doi.org/10.3390/v9070192 - 19 Jul 2017

Cited by 62 | Viewed by 8289

Abstract

Drosophila and extant species are the best-studied telomerase exception. In this organism, telomere elongation is coupled with targeted retrotransposition of Healing Transposon (HeT-A) and Telomere Associated Retrotransposon (TART) with sporadic additions of Telomere Associated and HeT-A Related (TAHRE), all three specialized non-Long Terminal [...] Read more.

Drosophila and extant species are the best-studied telomerase exception. In this organism, telomere elongation is coupled with targeted retrotransposition of Healing Transposon (HeT-A) and Telomere Associated Retrotransposon (TART) with sporadic additions of Telomere Associated and HeT-A Related (TAHRE), all three specialized non-Long Terminal Repeat (non-LTR) retrotransposons. These three very special retroelements transpose in head to tail arrays, always in the same orientation at the end of the chromosomes but never in interior locations. Apparently, retrotransposon and telomerase telomeres might seem very different, but a detailed view of their mechanisms reveals similarities explaining how the loss of telomerase in a Drosophila ancestor could successfully have been replaced by the telomere retrotransposons. In this review, we will discover that although HeT-A, TART, and TAHRE are still the only examples to date where their targeted transposition is perfectly tamed into the telomere biology of Drosophila, there are other examples of retrotransposons that manage to successfully integrate inside and at the end of telomeres. Because the aim of this special issue is viral integration at telomeres, understanding the base of the telomerase exceptions will help to obtain clues on similar strategies that mobile elements and viruses could have acquired in order to ensure their survival in the host genome. Full article

(This article belongs to the Special Issue Viruses and Telomeres)

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Open AccessArticle

Perturbation of Human T-Cell Leukemia Virus Type 1 Particle Morphology by Differential Gag Co-Packaging

by José O. Maldonado, Isaac Angert, Sheng Cao, Serkan Berk, Wei Zhang, Joachim D. Mueller and Louis M. Mansky

Viruses 2017, 9(7), 191; https://doi.org/10.3390/v9070191 - 19 Jul 2017

Cited by 6 | Viewed by 5051

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is an important cancer-causing human retrovirus that has infected approximately 15 million individuals worldwide. Many aspects of HTLV-1 replication, including virus particle structure and assembly, are poorly understood. Group-specific antigen (Gag) proteins labeled at the carboxy [...] Read more.

Human T-cell leukemia virus type 1 (HTLV-1) is an important cancer-causing human retrovirus that has infected approximately 15 million individuals worldwide. Many aspects of HTLV-1 replication, including virus particle structure and assembly, are poorly understood. Group-specific antigen (Gag) proteins labeled at the carboxy terminus with a fluorophore protein have been used extensively as a surrogate for fluorescence studies of retroviral assembly. How these tags affect Gag stoichiometry and particle morphology has not been reported in detail. In this study, we used an HTLV-1 Gag expression construct with the yellow fluorescence protein (YFP) fused to the carboxy-terminus as a surrogate for the HTLV-1 Gag-Pol to assess the effects of co-packaging of Gag and a Gag-YFP on virus-like particle (VLP) morphology and analyzed particles by cryogenic transmission electron microscopy (cryo-TEM). Scanning transmission electron microscopy (STEM) and fluorescence fluctuation spectroscopy (FFS) were also used to determine the Gag stoichiometry. We found that ratios of 3:1 (Gag:Gag-YFP) or greater resulted in a particle morphology indistinguishable from that of VLPs produced with the untagged HTLV-1 Gag, i.e., a mean diameter of ~113 nm and a mass of 220 MDa as determined by cryo-TEM and STEM, respectively. Furthermore, FFS analysis indicated that HTLV-1 Gag-YFP was incorporated into VLPs in a predictable manner at the 3:1 Gag:Gag-YFP ratio. Both STEM and FFS analyses found that the Gag copy number in VLPs produced with a 3:1 ratio of Gag:Gag-YFP was is in the range of 1500–2000 molecules per VLP. The observations made in this study indicate that biologically relevant Gag–Gag interactions occur between Gag and Gag-YFP at ratios of 3:1 or higher and create a Gag lattice structure in VLPs that is morphologically indistinguishable from that of VLPs produced with just untagged Gag. This information is useful for the quantitative analysis of Gag–Gag interactions that occur during virus particle assembly and in released immature particles. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessArticle

DNA-Interacting Characteristics of the Archaeal Rudiviral Protein SIRV2_Gp1

by Eveline Peeters, Maarten Boon, Clare Rollie, Ronnie G. Willaert, Marleen Voet, Malcolm F. White, David Prangishvili, Rob Lavigne and Tessa E.F. Quax

Viruses 2017, 9(7), 190; https://doi.org/10.3390/v9070190 - 18 Jul 2017

Cited by 12 | Viewed by 7160

Abstract

Whereas the infection cycles of many bacterial and eukaryotic viruses have been characterized in detail, those of archaeal viruses remain largely unexplored. Recently, studies on a few model archaeal viruses such as SIRV2 (Sulfolobus islandicus rod-shaped virus) have revealed an unusual lysis mechanism [...] Read more.

Whereas the infection cycles of many bacterial and eukaryotic viruses have been characterized in detail, those of archaeal viruses remain largely unexplored. Recently, studies on a few model archaeal viruses such as SIRV2 (Sulfolobus islandicus rod-shaped virus) have revealed an unusual lysis mechanism that involves the formation of pyramidal egress structures on the host cell surface. To expand understanding of the infection cycle of SIRV2, we aimed to functionally characterize gp1, which is a SIRV2 gene with unknown function. The SIRV2_Gp1 protein is highly expressed during early stages of infection and it is the only protein that is encoded twice on the viral genome. It harbours a helix-turn-helix motif and was therefore hypothesized to bind DNA. The DNA-binding behavior of SIRV2_Gp1 was characterized with electrophoretic mobility shift assays and atomic force microscopy. We provide evidence that the protein interacts with DNA and that it forms large aggregates, thereby causing extreme condensation of the DNA. Furthermore, the N-terminal domain of the protein mediates toxicity to the viral host Sulfolobus. Our findings may lead to biotechnological applications, such as the development of a toxic peptide for the containment of pathogenic bacteria, and add to our understanding of the Rudiviral infection cycle. Full article

(This article belongs to the Special Issue Viruses of Microbes)

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Open AccessArticle

Synchronous Langat Virus Infection of Haemaphysalis longicornis Using Anal Pore Microinjection

by Melbourne Rio Talactac, Kentaro Yoshii, Emmanuel Pacia Hernandez, Kodai Kusakisako, Remil Linggatong Galay, Kozo Fujisaki, Masami Mochizuki and Tetsuya Tanaka

Viruses 2017, 9(7), 189; https://doi.org/10.3390/v9070189 - 17 Jul 2017

Cited by 12 | Viewed by 6700

Abstract

The tick-borne encephalitis virus (TBEV) serocomplex of flaviviruses consists of arboviruses that cause important diseases in animals and humans. The transmission of this group of viruses is commonly associated with tick species such as Ixodes spp., Dermacentor spp., and Hyalomma spp. In the [...] Read more.

The tick-borne encephalitis virus (TBEV) serocomplex of flaviviruses consists of arboviruses that cause important diseases in animals and humans. The transmission of this group of viruses is commonly associated with tick species such as Ixodes spp., Dermacentor spp., and Hyalomma spp. In the case of Haemaphysalis longicornis, the detection and isolation of flaviviruses have been previously reported. However, studies showing survival dynamics of any tick-borne flavivirus in H. longicornis are still lacking. In this study, an anal pore microinjection method was used to infect adult H. longicornis with Langat virus (LGTV), a naturally attenuated member of the TBEV serocomplex. LGTV detection in ticks was done by real-time PCR, virus isolation, and indirect immunofluorescent antibody test. The maximum viral titer was recorded at 28 days post-inoculation, and midgut cells were shown to be the primary replication site. The tick can also harbor the virus for at least 120 days and can successfully transmit LGTV to susceptible mice as confirmed by detection of LGTV antibodies. However, no transovarial transmission was observed from the egg and larval samples. Taken together, our results highly suggest that anal pore microinjection can be an effective method in infecting adult H. longicornis, which can greatly assist in our efforts to study tick and virus interactions. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessArticle

Novel Fri1-like Viruses Infecting Acinetobacter baumannii—vB_AbaP_AS11 and vB_AbaP_AS12—Characterization, Comparative Genomic Analysis, and Host-Recognition Strategy.

by Anastasia V. Popova, Daria G. Lavysh, Evgeniy I. Klimuk, Mikhail V. Edelstein, Alexander G. Bogun, Mikhail M. Shneider, Artemiy E. Goncharov, Sergey V. Leonov and Konstantin V. Severinov

Viruses 2017, 9(7), 188; https://doi.org/10.3390/v9070188 - 17 Jul 2017

Cited by 35 | Viewed by 10810

Abstract

Acinetobacter baumannii is a gram-negative, non-fermenting aerobic bacterium which is often associated with hospital-acquired infections and known for its ability to develop resistance to antibiotics, form biofilms, and survive for long periods in hospital environments. In this study, we present two novel viruses, [...] Read more.

Acinetobacter baumannii is a gram-negative, non-fermenting aerobic bacterium which is often associated with hospital-acquired infections and known for its ability to develop resistance to antibiotics, form biofilms, and survive for long periods in hospital environments. In this study, we present two novel viruses, vB_AbaP_AS11 and vB_AbaP_AS12, specifically infecting and lysing distinct multidrug-resistant clinical A. baumannii strains with K19 and K27 capsular polysaccharide structures, respectively. Both phages demonstrate rapid adsorption, short latent periods, and high burst sizes in one-step growth experiments. The AS11 and AS12 linear double-stranded DNA genomes of 41,642 base pairs (bp) and 41,402 bp share 86.3% nucleotide sequence identity with the most variable regions falling in host receptor–recognition genes. These genes encode tail spikes possessing depolymerizing activities towards corresponding capsular polysaccharides which are the primary bacterial receptors. We described AS11 and AS12 genome organization and discuss the possible regulation of transcription. The overall genomic architecture and gene homology analyses showed that the phages are new representatives of the recently designated Fri1virus genus of the Autographivirinae subfamily within the Podoviridae family. Full article

(This article belongs to the Section Bacterial Viruses)

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Open AccessCommunication

Molecular Mechanisms of Human Papillomavirus Induced Skin Carcinogenesis

by Martin Hufbauer and Baki Akgül

Viruses 2017, 9(7), 187; https://doi.org/10.3390/v9070187 - 14 Jul 2017

Cited by 55 | Viewed by 12635

Abstract

Infection of the cutaneous skin with human papillomaviruses (HPV) of genus betapapillomavirus (βHPV) is associated with the development of premalignant actinic keratoses and squamous cell carcinoma. Due to the higher viral loads of βHPVs in actinic keratoses than in cancerous lesions, it is [...] Read more.

Infection of the cutaneous skin with human papillomaviruses (HPV) of genus betapapillomavirus (βHPV) is associated with the development of premalignant actinic keratoses and squamous cell carcinoma. Due to the higher viral loads of βHPVs in actinic keratoses than in cancerous lesions, it is currently discussed that these viruses play a carcinogenic role in cancer initiation. In vitro assays performed to characterize the cell transforming activities of high-risk HPV types of genus alphapapillomavirus have markedly contributed to the present knowledge on their oncogenic functions. However, these assays failed to detect oncogenic functions of βHPV early proteins. They were not suitable for investigations aiming to study the interactive role of βHPV positive epidermis with mesenchymal cells and the extracellular matrix. This review focuses on βHPV gene functions with special focus on oncogenic mechanisms that may be relevant for skin cancer development. Full article

(This article belongs to the Special Issue Expert Views on HPV Infection)

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Open AccessReview

Targeting Pattern Recognition Receptors (PRR) for Vaccine Adjuvantation: From Synthetic PRR Agonists to the Potential of Defective Interfering Particles of Viruses

by Andri Vasou, Nazife Sultanoglu, Stephen Goodbourn, Richard E. Randall and Leondios G. Kostrikis

Viruses 2017, 9(7), 186; https://doi.org/10.3390/v9070186 - 13 Jul 2017

Cited by 66 | Viewed by 10192

Abstract

Modern vaccinology has increasingly focused on non-living vaccines, which are more stable than live-attenuated vaccines but often show limited immunogenicity. Immunostimulatory substances, known as adjuvants, are traditionally used to increase the magnitude of protective adaptive immunity in response to a pathogen-associated antigen. Recently [...] Read more.

Modern vaccinology has increasingly focused on non-living vaccines, which are more stable than live-attenuated vaccines but often show limited immunogenicity. Immunostimulatory substances, known as adjuvants, are traditionally used to increase the magnitude of protective adaptive immunity in response to a pathogen-associated antigen. Recently developed adjuvants often include substances that stimulate pattern recognition receptors (PRRs), essential components of innate immunity required for the activation of antigen-presenting cells (APCs), which serve as a bridge between innate and adaptive immunity. Nearly all PRRs are potential targets for adjuvants. Given the recent success of toll-like receptor (TLR) agonists in vaccine development, molecules with similar, but additional, immunostimulatory activity, such as defective interfering particles (DIPs) of viruses, represent attractive candidates for vaccine adjuvants. This review outlines some of the recent advances in vaccine development related to the use of TLR agonists, summarizes the current knowledge regarding DIP immunogenicity, and discusses the potential applications of DIPs in vaccine adjuvantation. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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Open AccessReview

Vertebrate Reservoirs of Arboviruses: Myth, Synonym of Amplifier, or Reality?

by Goro Kuno, John S. Mackenzie, Sandra Junglen, Zdeněk Hubálek, Alexander Plyusnin and Duane J. Gubler

Viruses 2017, 9(7), 185; https://doi.org/10.3390/v9070185 - 13 Jul 2017

Cited by 53 | Viewed by 11340

Abstract

The rapid succession of the pandemic of arbovirus diseases, such as dengue, West Nile fever, chikungunya, and Zika fever, has intensified research on these and other arbovirus diseases worldwide. Investigating the unique mode of vector-borne transmission requires a clear understanding of the roles [...] Read more.

The rapid succession of the pandemic of arbovirus diseases, such as dengue, West Nile fever, chikungunya, and Zika fever, has intensified research on these and other arbovirus diseases worldwide. Investigating the unique mode of vector-borne transmission requires a clear understanding of the roles of vertebrates. One major obstacle to this understanding is the ambiguity of the arbovirus definition originally established by the World Health Organization. The paucity of pertinent information on arbovirus transmission at the time contributed to the notion that vertebrates played the role of reservoir in the arbovirus transmission cycle. Because this notion is a salient feature of the arbovirus definition, it is important to reexamine its validity. This review addresses controversial issues concerning vertebrate reservoirs and their role in arbovirus persistence in nature, examines the genesis of the problem from a historical perspective, discusses various unresolved issues from multiple points of view, assesses the present status of the notion in light of current knowledge, and provides options for a solution to resolve the issue. Full article

(This article belongs to the Section Invertebrate Viruses)

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Open AccessReview

Chromosomally Integrated Human Herpesvirus 6: Models of Viral Genome Release from the Telomere and Impacts on Human Health

by Michael L. Wood and Nicola J. Royle

Viruses 2017, 9(7), 184; https://doi.org/10.3390/v9070184 - 12 Jul 2017

Cited by 16 | Viewed by 6034

Abstract

Human herpesvirus 6A and 6B, alongside some other herpesviruses, have the striking capacity to integrate into telomeres, the terminal repeated regions of chromosomes. The chromosomally integrated forms, ciHHV-6A and ciHHV-6B, are proposed to be a state of latency and it has been shown [...] Read more.

Human herpesvirus 6A and 6B, alongside some other herpesviruses, have the striking capacity to integrate into telomeres, the terminal repeated regions of chromosomes. The chromosomally integrated forms, ciHHV-6A and ciHHV-6B, are proposed to be a state of latency and it has been shown that they can both be inherited if integration occurs in the germ line. The first step in full viral reactivation must be the release of the integrated viral genome from the telomere and here we propose various models of this release involving transcription of the viral genome, replication fork collapse, and t-circle mediated release. In this review, we also discuss the relationship between ciHHV-6 and the telomere carrying the insertion, particularly how the presence and subsequent partial or complete release of the ciHHV-6 genome may affect telomere dynamics and the risk of disease. Full article

(This article belongs to the Special Issue Viruses and Telomeres)

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Open AccessArticle

Variability of Emaravirus Species Associated with Sterility Mosaic Disease of Pigeonpea in India Provides Evidence of Segment Reassortment

by Basavaprabhu L. Patil, Meenakshi Dangwal and Ritesh Mishra

Viruses 2017, 9(7), 183; https://doi.org/10.3390/v9070183 - 11 Jul 2017

Cited by 29 | Viewed by 5549

Abstract

Sterility mosaic disease (SMD) of pigeonpea is a serious constraint for cultivation of pigeonpea in India and other South Asian countries. SMD of pigeonpea is associated with two distinct emaraviruses, Pigeonpea sterility mosaic virus 1 (PPSMV-1) and Pigeonpea sterility mosaic virus 2 (PPSMV-2), [...] Read more.

Sterility mosaic disease (SMD) of pigeonpea is a serious constraint for cultivation of pigeonpea in India and other South Asian countries. SMD of pigeonpea is associated with two distinct emaraviruses, Pigeonpea sterility mosaic virus 1 (PPSMV-1) and Pigeonpea sterility mosaic virus 2 (PPSMV-2), with genomes consisting of five and six negative-sense RNA segments, respectively. The recently published genome sequences of both PPSMV-1 and PPSMV-2 are from a single location, Patancheru from the state of Telangana in India. However, here we present the first report of sequence variability among 23 isolates of PPSMV-1 and PPSMV-2, collected from ten locations representing six states of India. Both PPSMV-1 and PPSMV-2 are shown to be present across India and to exhibit considerable sequence variability. Variability of RNA3 sequences was higher than the RNA4 sequences for both PPSMV-1 and PPSMV-2. Additionally, the sixth RNA segment (RNA6), previously reported to be associated with only PPSMV-2, is also associated with isolates of PPSMV-1. Multiplex reverse transcription PCR (RT-PCR) analyses show that PPSMV-1 and PPSMV-2 frequently occur as mixed infections. Further sequence analyses indicated the presence of reassortment of RNA4 between isolates of PPSMV-1 and PPSMV-2. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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Open AccessFeature PaperReview

The Interaction between Nidovirales and Autophagy Components

by Yingying Cong, Pauline Verlhac and Fulvio Reggiori

Viruses 2017, 9(7), 182; https://doi.org/10.3390/v9070182 - 11 Jul 2017

Cited by 32 | Viewed by 19208

Abstract

Autophagy is a conserved intracellular catabolic pathway that allows cells to maintain homeostasis through the degradation of deleterious components via specialized double-membrane vesicles called autophagosomes. During the past decades, it has been revealed that numerous pathogens, including viruses, usurp autophagy in order to [...] Read more.

Autophagy is a conserved intracellular catabolic pathway that allows cells to maintain homeostasis through the degradation of deleterious components via specialized double-membrane vesicles called autophagosomes. During the past decades, it has been revealed that numerous pathogens, including viruses, usurp autophagy in order to promote their propagation. Nidovirales are an order of enveloped viruses with large single-stranded positive RNA genomes. Four virus families (Arterividae, Coronaviridae, Mesoniviridae, and Roniviridae) are part of this order, which comprises several human and animal pathogens of medical and veterinary importance. In host cells, Nidovirales induce membrane rearrangements including autophagosome formation. The relevance and putative mechanism of autophagy usurpation, however, remain largely elusive. Here, we review the current knowledge about the possible interplay between Nidovirales and autophagy. Full article

(This article belongs to the Special Issue Viruses and Autophagy)

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Open AccessArticle

PCR-DGGE Analysis: Unravelling Complex Mixtures of Badnavirus Sequences Present in Yam Germplasm

by Aliyu A. Turaki, Moritz Bömer, Gonçalo Silva, P. Lava Kumar and Susan E. Seal

Viruses 2017, 9(7), 181; https://doi.org/10.3390/v9070181 - 11 Jul 2017

Cited by 11 | Viewed by 9860

Abstract

Badnaviruses (family Caulimoviridae, genus Badnavirus) have emerged as serious pathogens especially affecting the cultivation of tropical crops. Badnavirus sequences can be integrated in host genomes, complicating the detection of episomal infections and the assessment of viral genetic diversity in samples containing [...] Read more.

Badnaviruses (family Caulimoviridae, genus Badnavirus) have emerged as serious pathogens especially affecting the cultivation of tropical crops. Badnavirus sequences can be integrated in host genomes, complicating the detection of episomal infections and the assessment of viral genetic diversity in samples containing a complex mixture of sequences. Yam (Dioscorea spp.) plants are hosts to a diverse range of badnavirus species, and recent findings have suggested that mixed infections occur frequently in West African yam germplasm. Historically, the determination of the diversity of badnaviruses present in yam breeding lines has been achieved by cloning and sequencing of polymerase chain reaction (PCR) products. In this study, the molecular diversity of partial reverse transcriptase (RT)-ribonuclease H (RNaseH) sequences from yam badnaviruses was analysed using PCR-dependent denaturing gradient gel electrophoresis (PCR-DGGE). This resulted in the identification of complex ‘fingerprints’ composed of multiple sequences of Dioscorea bacilliform viruses (DBVs). Many of these sequences show high nucleotide identities to endogenous DBV (eDBV) sequences deposited in GenBank, and fall into six monophyletic species groups. Our findings highlight PCR-DGGE as a powerful tool in badnavirus diversity studies enabling a rapid indication of sequence diversity as well as potential candidate integrated sequences revealed by their conserved nature across germplasm. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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Open AccessReview

Telomerase Induction in HPV Infection and Oncogenesis

by Rachel Katzenellenbogen

Viruses 2017, 9(7), 180; https://doi.org/10.3390/v9070180 - 10 Jul 2017

Cited by 40 | Viewed by 6465

Abstract

Telomerase extends the repetitive DNA at the ends of linear chromosomes, and it is normally active in stem cells. When expressed in somatic diploid cells, it can lead to cellular immortalization. Human papillomaviruses (HPVs) are associated with and high-risk for cancer activate telomerase [...] Read more.

Telomerase extends the repetitive DNA at the ends of linear chromosomes, and it is normally active in stem cells. When expressed in somatic diploid cells, it can lead to cellular immortalization. Human papillomaviruses (HPVs) are associated with and high-risk for cancer activate telomerase through the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT). The expression of hTERT is affected by both high-risk HPVs, E6 and E7. Seminal studies over the last two decades have identified the transcriptional, epigenetic, and post-transcriptional roles high-risk E6 and E7 have in telomerase induction. This review will summarize these findings during infection and highlight the importance of telomerase activation as an oncogenic pathway in HPV-associated cancer development and progression. Full article

(This article belongs to the Special Issue Expert Views on HPV Infection)

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Open AccessArticle

Almond Skin Extracts Abrogate HSV-1 Replication by Blocking Virus Binding to the Cell

by Carlo Bisignano, Giuseppina Mandalari, Antonella Smeriglio, Domenico Trombetta, Maria Musarra Pizzo, Rosamaria Pennisi and Maria Teresa Sciortino

Viruses 2017, 9(7), 178; https://doi.org/10.3390/v9070178 - 10 Jul 2017

Cited by 52 | Viewed by 7398

Abstract

The aim of the present research was to determine the effect of almond skin extracts on herpes simplex virus 1 (HSV-1) replication. Drug-resistant strains of HSV frequently develop following therapeutic treatment. Therefore, the discovery of novel anti-HSV drugs deserves great effort. Here, we [...] Read more.

The aim of the present research was to determine the effect of almond skin extracts on herpes simplex virus 1 (HSV-1) replication. Drug-resistant strains of HSV frequently develop following therapeutic treatment. Therefore, the discovery of novel anti-HSV drugs deserves great effort. Here, we tested both natural (NS) and blanched (BS) polyphenols-rich almond skin extracts against HSV-1. HPLC analysis showed that the prevalent compounds in NS and BS extracts contributing to their antioxidant activity were quercetin, epicatechin and catechin. Results of cell viability indicated that NS and BS extracts were not toxic to cultured Vero cells. Furthermore, NS extracts were more potent inhibitors of HSV-1 than BS extracts, and this trend was in agreement with different concentrations of flavonoids. The plaque forming assay, Western blot and real-time PCR were used to demonstrate that NS extracts were able to block the production of infectious HSV-1 particles. In addition, the viral binding assay demonstrated that NS extracts inhibited HSV-1 adsorption to Vero cells. Our conclusion is that natural products from almond skin extracts are an extraordinary source of antiviral agents and provide a novel treatment against HSV-1 infections. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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Open AccessArticle

Development of Polioencephalomyelitis in Cesarean-Derived Colostrum-Deprived Pigs Following Experimental Inoculation with Either Teschovirus A Serotype 2 or Serotype 11

by Franco Matias Ferreyra, Bailey Arruda, Gregory Stevenson, Kent Schwartz, Darin Madson, Kyoung-Jin Yoon, Jianqiang Zhang, Pablo Piñeyro, Qi Chen and Paulo Arruda

Viruses 2017, 9(7), 179; https://doi.org/10.3390/v9070179 - 8 Jul 2017

Cited by 16 | Viewed by 5060

Abstract

Teschovirus encephalomyelitis is a sporadic disease associated with Teschovirus A (PTV) serotype 1 and, less frequently, other serotypes. In recent years, the number of cases submitted to the Iowa State University Veterinary Diagnostic Laboratory with a history of posterior paresis has increased. Submission [...] Read more.

Teschovirus encephalomyelitis is a sporadic disease associated with Teschovirus A (PTV) serotype 1 and, less frequently, other serotypes. In recent years, the number of cases submitted to the Iowa State University Veterinary Diagnostic Laboratory with a history of posterior paresis has increased. Submission histories from various regions of the United States suggest a trend for clinical disease to persist in herds and affect a wider age-range of pigs than historically reported. Polioencephalitis and/or myelitis was consistently present and PTV was detected in affected neural tissue by PCR in a portion of cases. Sequencing from two clinical cases identified PTV-2 and PTV-11. To assess neuropathogenicity of these isolates, 5-week-old cesarean derived and colostrum-deprived pigs were assigned to three groups: negative control (n = 4), PTV-2-inoculated (n = 7), and PTV-11-inoculated (n = 7). Three PTV-2-inoculated pigs developed mild incoordination of the hind limbs, one of which progressed to posterior ataxia. While all PTV-11-inoculated pigs showed severe neurological signs consistent with Teschovirus encephalomyelitis, no evidences of neurological signs were observed in sham-inoculated animals. All PTV-2- and PTV-11-inoculated pigs had microscopic lesions consistent with Teschovirus encephalomyelitis. To our knowledge, this is the first description of PTV-11 and experimental study demonstrating the neuropathogenicity of PTV-11 in the United States. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessArticle

Porcine Epidemic Diarrhea in Europe: In-Detail Analyses of Disease Dynamics and Molecular Epidemiology

by Dennis Hanke, Anne Pohlmann, Carola Sauter-Louis, Dirk Höper, Julia Stadler, Mathias Ritzmann, Adi Steinrigl, Bernd-Andreas Schwarz, Valerij Akimkin, Robert Fux, Sandra Blome and Martin Beer

Viruses 2017, 9(7), 177; https://doi.org/10.3390/v9070177 - 6 Jul 2017

Cited by 63 | Viewed by 7838

Abstract

Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease of swine caused by the eponymous virus (PEDV) which belongs to the genus Alphacoronavirus within the Coronaviridae virus family. Following the disastrous outbreaks in Asia and the United States, PEDV has [...] Read more.

Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease of swine caused by the eponymous virus (PEDV) which belongs to the genus Alphacoronavirus within the Coronaviridae virus family. Following the disastrous outbreaks in Asia and the United States, PEDV has been detected also in Europe. In order to better understand the overall situation, the molecular epidemiology, and factors that might influence the most variable disease impact; 40 samples from swine feces were collected from different PED outbreaks in Germany and other European countries and sequenced by shot-gun next-generation sequencing. A total of 38 new PEDV complete coding sequences were generated. When compared on a global scale, all investigated sequences from Central and South-Eastern Europe formed a rather homogeneous PEDV S INDEL cluster, suggesting a recent re-introduction. However, in-detail analyses revealed two new clusters and putative ancestor strains. Based on the available background data, correlations between clusters and location, farm type or clinical presentation could not be established. Additionally, the impact of secondary infections was explored using the metagenomic data sets. While several coinfections were observed, no correlation was found with disease courses. However, in addition to the PEDV genomes, ten complete viral coding sequences from nine different data sets were reconstructed each representing new virus strains. In detail, three pasivirus A strains, two astroviruses, a porcine sapelovirus, a kobuvirus, a porcine torovirus, a posavirus, and an enterobacteria phage were almost fully sequenced. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessReview

Interplay between Autophagy, Exosomes and HIV-1 Associated Neurological Disorders: New Insights for Diagnosis and Therapeutic Applications

by Chet Raj Ojha, Jessica Lapierre, Myosotys Rodriguez, Seth M. Dever, Mohammad Asad Zadeh, Catherine DeMarino, Michelle L. Pleet, Fatah Kashanchi and Nazira El-Hage

Viruses 2017, 9(7), 176; https://doi.org/10.3390/v9070176 - 6 Jul 2017

Cited by 48 | Viewed by 9425

Abstract

The autophagy–lysosomal pathway mediates a degradative process critical in the maintenance of cellular homeostasis as well as the preservation of proper organelle function by selective removal of damaged proteins and organelles. In some situations, cells remove unwanted or damaged proteins and RNAs through [...] Read more.

The autophagy–lysosomal pathway mediates a degradative process critical in the maintenance of cellular homeostasis as well as the preservation of proper organelle function by selective removal of damaged proteins and organelles. In some situations, cells remove unwanted or damaged proteins and RNAs through the release to the extracellular environment of exosomes. Since exosomes can be transferred from one cell to another, secretion of unwanted material to the extracellular environment in exosomes may have an impact, which can be beneficial or detrimental, in neighboring cells. Exosome secretion is under the influence of the autophagic system, and stimulation of autophagy can inhibit exosomal release and vice versa. Neurons are particularly vulnerable to degeneration, especially as the brain ages, and studies indicate that imbalances in genes regulating autophagy are a common feature of many neurodegenerative diseases. Cognitive and motor disease associated with severe dementia and neuronal damage is well-documented in the brains of HIV-infected individuals. Neurodegeneration seen in the brain in HIV-1 infection is associated with dysregulation of neuronal autophagy. In this paradigm, we herein provide an overview on the role of autophagy in HIV-associated neurodegenerative disease, focusing particularly on the effect of autophagy modulation on exosomal release of HIV particles and how this interplay impacts HIV infection in the brain. Specific autophagy–regulating agents are being considered for therapeutic treatment and prevention of a broad range of human diseases. Various therapeutic strategies for modulating specific stages of autophagy and the current state of drug development for this purpose are also evaluated. Full article

(This article belongs to the Special Issue Viruses and Autophagy)

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Open AccessArticle

SOX2 as a New Regulator of HPV16 Transcription

by Imelda Martínez-Ramírez, Víctor Del-Castillo-Falconi, Irma B. Mitre-Aguilar, Alfredo Amador-Molina, Adela Carrillo-García, Elizabeth Langley, Alejandro Zentella-Dehesa, Ernesto Soto-Reyes, Alejandro García-Carrancá, Luis A. Herrera and Marcela Lizano

Viruses 2017, 9(7), 175; https://doi.org/10.3390/v9070175 - 5 Jul 2017

Cited by 18 | Viewed by 5533

Abstract

Persistent infections with high-risk human papillomavirus (HPV) constitute the main risk factor for cervical cancer development. HPV16 is the most frequent type associated to squamous cell carcinomas (SCC), followed by HPV18. The long control region (LCR) in the HPV genome contains the replication [...] Read more.

Persistent infections with high-risk human papillomavirus (HPV) constitute the main risk factor for cervical cancer development. HPV16 is the most frequent type associated to squamous cell carcinomas (SCC), followed by HPV18. The long control region (LCR) in the HPV genome contains the replication origin and sequences recognized by cellular transcription factors (TFs) controlling viral transcription. Altered expression of E6 and E7 viral oncogenes, modulated by the LCR, causes modifications in cellular pathways such as proliferation, leading to malignant transformation. The aim of this study was to identify specific TFs that could contribute to the modulation of high-risk HPV transcriptional activity, related to the cellular histological origin. We identified sex determining region Y (SRY)-box 2 (SOX2) response elements present in HPV16-LCR. SOX2 binding to the LCR was demonstrated by in vivo and in vitro assays. The overexpression of this TF repressed HPV16-LCR transcriptional activity, as shown through reporter plasmid assays and by the down-regulation of endogenous HPV oncogenes. Site-directed mutagenesis revealed that three putative SOX2 binding sites are involved in the repression of the LCR activity. We propose that SOX2 acts as a transcriptional repressor of HPV16-LCR, decreasing the expression of E6 and E7 oncogenes in a SCC context. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessFeature PaperReview

Virus/Host Cell Crosstalk in Hypoxic HPV-Positive Cancer Cells

by Karin Hoppe-Seyler, Julia Mändl, Svenja Adrian, Bianca J. Kuhn and Felix Hoppe-Seyler

Viruses 2017, 9(7), 174; https://doi.org/10.3390/v9070174 - 5 Jul 2017

Cited by 10 | Viewed by 8093

Abstract

Oncogenic types of human papillomaviruses (HPVs) are major human carcinogens. The expression of the viral E6/E7 oncogenes plays a key role for HPV-linked oncogenesis. It recently has been found that low oxygen concentrations (“hypoxia”), as present in sub-regions of HPV-positive cancers, [...] Read more.

Oncogenic types of human papillomaviruses (HPVs) are major human carcinogens. The expression of the viral E6/E7 oncogenes plays a key role for HPV-linked oncogenesis. It recently has been found that low oxygen concentrations (“hypoxia”), as present in sub-regions of HPV-positive cancers, strongly affect the interplay between the HPV oncogenes and their transformed host cell. As a result, a state of dormancy is induced in hypoxic HPV-positive cancer cells, which is characterized by a shutdown of viral oncogene expression and a proliferative arrest that can be reversed by reoxygenation. In this review, these findings are put into the context of the current concepts of both HPV-linked carcinogenesis and of the effects of hypoxia on tumor biology. Moreover, we discuss the consequences for the phenotype of HPV-positive cancer cells as well as for their clinical behavior and response towards established and prospective therapeutic strategies. Full article

(This article belongs to the Special Issue Expert Views on HPV Infection)

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Open AccessReview

Complex Virus–Host Interactions Involved in the Regulation of Classical Swine Fever Virus Replication: A Minireview

by Su Li, Jinghan Wang, Qian Yang, Muhammad Naveed Anwar, Shaoxiong Yu and Hua-Ji Qiu

Viruses 2017, 9(7), 171; https://doi.org/10.3390/v9070171 - 5 Jul 2017

Cited by 29 | Viewed by 11190

Abstract

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs in many countries. Viruses are small intracellular parasites and thus rely on the cellular factors for replication. Fundamental aspects of CSFV–host interactions [...] Read more.

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs in many countries. Viruses are small intracellular parasites and thus rely on the cellular factors for replication. Fundamental aspects of CSFV–host interactions have been well described, such as factors contributing to viral attachment, modulation of genomic replication and translation, antagonism of innate immunity, and inhibition of cell apoptosis. However, those host factors that participate in the viral entry, assembly, and release largely remain to be elucidated. In this review, we summarize recent progress in the virus–host interactions involved in the life cycle of CSFV and analyze the potential mechanisms of viral entry, assembly, and release. We conclude with future perspectives and highlight areas that require further understanding. Full article

(This article belongs to the Special Issue Porcine Viruses)

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Open AccessReview

Telomeres and Telomerase: Role in Marek’s Disease Virus Pathogenesis, Integration and Tumorigenesis

by Ahmed Kheimar, Renato L. Previdelli, Darren J. Wight and Benedikt B. Kaufer

Viruses 2017, 9(7), 173; https://doi.org/10.3390/v9070173 - 4 Jul 2017

Cited by 22 | Viewed by 7074

Abstract

Telomeres protect the ends of vertebrate chromosomes from deterioration and consist of tandem nucleotide repeats (TTAGGG)_n that are associated with a number of proteins. Shortening of the telomeres occurs during genome replication, thereby limiting the replication potential of somatic cells. To counteract [...] Read more.

Telomeres protect the ends of vertebrate chromosomes from deterioration and consist of tandem nucleotide repeats (TTAGGG)_n that are associated with a number of proteins. Shortening of the telomeres occurs during genome replication, thereby limiting the replication potential of somatic cells. To counteract this shortening, vertebrates encode the telomerase complex that maintains telomere length in certain cell types via de novo addition of telomeric repeats. Several herpesviruses, including the highly oncogenic alphaherpesvirus Marek’s disease virus (MDV), harbor telomeric repeats (TMR) identical to the host telomere sequences at the ends of their linear genomes. These TMR facilitate the integration of the MDV genome into host telomeres during latency, allowing the virus to persist in the host for life. Integration into host telomeres is critical for disease and tumor induction by MDV, but also enables efficient reactivation of the integrated virus genome. In addition to the TMR, MDV also encodes a telomerase RNA subunit (vTR) that shares 88% sequence identity with the telomerase RNA in chicken (chTR). vTR is highly expressed during all stages of the virus lifecycle, enhances telomerase activity and plays an important role in MDV-induced tumor formation. This review will focus on the recent advances in understanding the role of viral TMR and vTR in MDV pathogenesis, integration and tumorigenesis. Full article

(This article belongs to the Special Issue Viruses and Telomeres)

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Open AccessFeature PaperReview

Hepatitis Delta Virus: Replication Strategy and Upcoming Therapeutic Options for a Neglected Human Pathogen

by Florian A. Lempp and Stephan Urban

Viruses 2017, 9(7), 172; https://doi.org/10.3390/v9070172 - 4 Jul 2017

Cited by 31 | Viewed by 19363

Abstract

The human Hepatitis Delta Virus (HDV) is unique among all viral pathogens. Encoding only one protein (Hepatitis Delta Antigen; HDAg) within its viroid-like self-complementary RNA, HDV constitutes the smallest known virus in the animal kingdom. To disseminate in its host, HDV depends on [...] Read more.

The human Hepatitis Delta Virus (HDV) is unique among all viral pathogens. Encoding only one protein (Hepatitis Delta Antigen; HDAg) within its viroid-like self-complementary RNA, HDV constitutes the smallest known virus in the animal kingdom. To disseminate in its host, HDV depends on a helper virus, the human Hepatitis B virus (HBV), which provides the envelope proteins required for HDV assembly. HDV affects an estimated 15–20 million out of the 240 million chronic HBV-carriers and disperses unequally in disparate geographical regions of the world. The disease it causes (chronic Hepatitis D) presents as the most severe form of viral hepatitis, leading to accelerated progression of liver dysfunction including cirrhosis and hepatocellular carcinoma and a high mortality rate. The lack of approved drugs interfering with specific steps of HDV replication poses a high burden for gaining insights into the molecular biology of the virus and, consequently, the development of specific novel medications that resiliently control HDV replication or, in the best case, functionally cure HDV infection or HBV/HDV co-infection. This review summarizes our current knowledge of HBV molecular biology, presents an update on novel cell culture and animal models to study the virus and provides updates on the clinical development of the three developmental drugs Lonafarnib, REP2139-Ca and Myrcludex B. Full article

(This article belongs to the Special Issue Recent Advances in Hepatitis B Virus Research)

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Open AccessArticle

2BC Non-Structural Protein of Enterovirus A71 Interacts with SNARE Proteins to Trigger Autolysosome Formation

by Jeffrey K. F. Lai, I-Ching Sam, Pauline Verlhac, Joël Baguet, Eeva-Liisa Eskelinen, Mathias Faure and Yoke Fun Chan

Viruses 2017, 9(7), 169; https://doi.org/10.3390/v9070169 - 4 Jul 2017

Cited by 27 | Viewed by 8016

Abstract

Viruses have evolved unique strategies to evade or subvert autophagy machinery. Enterovirus A71 (EV-A71) induces autophagy during infection in vitro and in vivo. In this study, we report that EV-A71 triggers autolysosome formation during infection in human rhabdomyosarcoma (RD) cells to facilitate its [...] Read more.

Viruses have evolved unique strategies to evade or subvert autophagy machinery. Enterovirus A71 (EV-A71) induces autophagy during infection in vitro and in vivo. In this study, we report that EV-A71 triggers autolysosome formation during infection in human rhabdomyosarcoma (RD) cells to facilitate its replication. Blocking autophagosome-lysosome fusion with chloroquine inhibited virus RNA replication, resulting in lower viral titres, viral RNA copies and viral proteins. Overexpression of the non-structural protein 2BC of EV-A71 induced autolysosome formation. Yeast 2-hybrid and co-affinity purification assays showed that 2BC physically and specifically interacted with a N-ethylmaleimide-sensitive factor attachment receptor (SNARE) protein, syntaxin-17 (STX17). Co-immunoprecipitation assay further showed that 2BC binds to SNARE proteins, STX17 and synaptosome associated protein 29 (SNAP29). Transient knockdown of STX17, SNAP29, and microtubule-associated protein 1 light chain 3B (LC3B), crucial proteins in the fusion between autophagosomes and lysosomes) as well as the lysosomal-associated membrane protein 1 (LAMP1) impaired production of infectious EV-A71 in RD cells. Collectively, these results demonstrate that the generation of autolysosomes triggered by the 2BC non-structural protein is important for EV-A71 replication, revealing a potential molecular pathway targeted by the virus to exploit autophagy. This study opens the possibility for the development of novel antivirals that specifically target 2BC to inhibit formation of autolysosomes during EV-A71 infection. Full article

(This article belongs to the Special Issue Viruses and Autophagy)

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Open AccessReview

Update on Senecavirus Infection in Pigs

by Raquel A. Leme, Alice F. Alfieri and Amauri A. Alfieri

Viruses 2017, 9(7), 170; https://doi.org/10.3390/v9070170 - 3 Jul 2017

Cited by 79 | Viewed by 11600

Abstract

Senecavirus A (SVA) is a positive-sense single-stranded RNA virus that belongs to the Senecavirus genus within the Picornaviridae family. The virus has been silently circulating in pig herds of the USA since 1988. However, cases of senecavirus-associated vesicular disease were reported in Canada [...] Read more.

Senecavirus A (SVA) is a positive-sense single-stranded RNA virus that belongs to the Senecavirus genus within the Picornaviridae family. The virus has been silently circulating in pig herds of the USA since 1988. However, cases of senecavirus-associated vesicular disease were reported in Canada in 2007 and in the USA in 2012. Since late 2014 and early 2015, an increasing number of senecavirus outbreaks have been reported in pigs in different producing categories, with this virus being detected in Brazil, China, and Thailand. Considering the novel available data on senecavirus infection and disease, 2015 may be a divisor in the epidemiology of the virus. Among the aspects that reinforce this hypothesis are the geographical distribution of the virus, the affected pig-producing categories, clinical signs associated with the infection, and disease severity. This review presents the current knowledge regarding the senecavirus infection and disease, especially in the last two years. Senecavirus epidemiology, pathogenic potential, host immunological response, diagnosis, and prophylaxis and control measures are addressed. Perspectives are focused on the need for complete evolutionary, epidemiological and pathogenic data and the capability for an immediate diagnosis of senecavirus infection. The health risks inherent in the swine industry cannot be neglected. Full article

(This article belongs to the Special Issue Porcine Viruses)

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Open AccessArticle

Crystal Structure of the Carboxy-Terminal Region of the Bacteriophage T4 Proximal Long Tail Fiber Protein Gp34

by Meritxell Granell, Mikiyoshi Namura, Sara Alvira, Shuji Kanamaru and Mark J. Van Raaij

Viruses 2017, 9(7), 168; https://doi.org/10.3390/v9070168 - 30 Jun 2017

Cited by 21 | Viewed by 8479

Abstract

Long tail fibers of bacteriophage T4 are formed by proteins gp34, gp35, gp36, and gp37, with gp34 located at the phage-proximal end and gp37 at the phage-distal, receptor-binding end. We have solved the structure of the carboxy-terminal region of gp34, consisting of amino [...] Read more.

Long tail fibers of bacteriophage T4 are formed by proteins gp34, gp35, gp36, and gp37, with gp34 located at the phage-proximal end and gp37 at the phage-distal, receptor-binding end. We have solved the structure of the carboxy-terminal region of gp34, consisting of amino acids 894–1289, by single-wavelength anomalous diffraction and extended the structure to amino acids 744–1289 using data collected from crystals containing longer gp34-fragments. The structure reveals three repeats of a mixed α-β fibrous domain in residues 744 to 877. A triple-helical neck connects to an extended triple β-helix domain (amino acids 900–1127) punctuated by two β-prism domains. Next, a β-prism domain decorated with short helices and extended β-helices is present (residues 1146–1238), while the C-terminal end is capped with another short β-helical region and three β-hairpins. The structure provides insight into the stability of the fibrous gp34 protein. Full article

(This article belongs to the Special Issue Viruses of Microbes)

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Open AccessFeature PaperArticle

Rotavirus Genomic RNA Complex Forms via Specific RNA–RNA Interactions: Disruption of RNA Complex Inhibits Virus Infectivity

by Teodoro Fajardo Jr., Po-Yu Sung, Cristina C. Celma and Polly Roy

Viruses 2017, 9(7), 167; https://doi.org/10.3390/v9070167 - 29 Jun 2017

Cited by 23 | Viewed by 5758

Abstract

Rotavirus (RV), a member of the Reoviridae family, causes infection in children and infants, with high morbidity and mortality. To be viable, the virus particle must package a set of eleven RNA segments. In order to understand the packaging mechanism, here, we co-synthesized [...] Read more.

Rotavirus (RV), a member of the Reoviridae family, causes infection in children and infants, with high morbidity and mortality. To be viable, the virus particle must package a set of eleven RNA segments. In order to understand the packaging mechanism, here, we co-synthesized sets of RNA segments in vitro in different combinations and detected by two alternate methods: the electrophoretic mobility shift assay (EMSA) and the RNA-bead pull-down assay. We showed that viral positive-sense RNA segments interact with each other in a specific manner, forming RNA complexes, and that the RNA–RNA interactions followed a sequential order initiated by small RV segments. Further, we demonstrated that RNA complexes were perturbed by targeted specific antisense oligoribonucleotides (ORNs) complementary to short RNA sequences, indicating that the RNA–RNA interactions between different segments were sequence-specific. The same inhibitory ORNs also had the capability to inhibit virus replication. The combined in vitro and in vivo data inferred that RNA–RNA interactions and specific complex formation are essential for sorting different segments, possibly prior to, or during, genome packaging. As genome assembly is a universal requirement in the Reoviridae family, this work offers an approach towards a further understanding of the sorting and packaging mechanisms of RV and related dsRNA (double-stranded RNA) viruses. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessArticle

Systemic Propagation of a Fluorescent Infectious Clone of a Polerovirus Following Inoculation by Agrobacteria and Aphids

by Sylvaine Boissinot, Elodie Pichon, Céline Sorin, Céline Piccini, Danièle Scheidecker, Véronique Ziegler-Graff and Véronique Brault

Viruses 2017, 9(7), 166; https://doi.org/10.3390/v9070166 - 29 Jun 2017

Cited by 20 | Viewed by 6501

Abstract

A fluorescent viral clone of the polerovirus Turnip yellows virus (TuYV) was engineered by introducing the Enhanced Green Fluorescent Protein (EGFP) sequence into the non-structural domain sequence of the readthrough protein, a minor capsid protein. The resulting recombinant virus, referred to as TuYV-RT [...] Read more.

A fluorescent viral clone of the polerovirus Turnip yellows virus (TuYV) was engineered by introducing the Enhanced Green Fluorescent Protein (EGFP) sequence into the non-structural domain sequence of the readthrough protein, a minor capsid protein. The resulting recombinant virus, referred to as TuYV-RT_GFP, was infectious in several plant species when delivered by agroinoculation and invaded efficiently non-inoculated leaves. As expected for poleroviruses, which infect only phloem cells, the fluorescence emitted by TuYV-RT_GFP was restricted to the vasculature of infected plants. In addition, TuYV-RT_GFP was aphid transmissible and enabled the observation of the initial sites of infection in the phloem after aphid probing in epidermal cells. The aphid-transmitted virus moved efficiently to leaves distant from the inoculation sites and importantly retained the EGFP sequence in the viral genome. This work reports on the first engineered member in the Luteoviridae family that can be visualized by fluorescence emission in systemic leaves of different plant species after agroinoculation or aphid transmission. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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Open AccessArticle

Effective Suckling C57BL/6, Kunming, and BALB/c Mouse Models with Remarkable Neurological Manifestation for Zika Virus Infection

by Jianhai Yu, Xuling Liu, Changwen Ke, Qinghua Wu, Weizhi Lu, Zhiran Qin, Xiaoen He, Yujing Liu, Jieli Deng, Suiqi Xu, Ying Li, Li Zhu, Chengsong Wan, Qiwei Zhang, Weiwei Xiao, Qian Xie, Bao Zhang and Wei Zhao

Viruses 2017, 9(7), 165; https://doi.org/10.3390/v9070165 - 29 Jun 2017

Cited by 30 | Viewed by 8035

Abstract

Since 2015, 84 countries and territories reported evidence of vector-borne Zika Virus (ZIKV) transmission. The World Health Organization (WHO) declared that ZIKV and associated consequences especially the neurological autoimmune disorder Guillain–Barré syndrome (GBS) and microcephaly will remain a significant enduring public health challenge [...] Read more.

Since 2015, 84 countries and territories reported evidence of vector-borne Zika Virus (ZIKV) transmission. The World Health Organization (WHO) declared that ZIKV and associated consequences especially the neurological autoimmune disorder Guillain–Barré syndrome (GBS) and microcephaly will remain a significant enduring public health challenge requiring intense action. We apply a standardization of the multi-subcutaneous dorsal inoculation method to systematically summarize clinical neurological manifestation, viral distribution, and tissue damage during the progress of viremia and systemic spread in suckling mouse models. We found that C57BL/6 and Kunming mice (KM) both showed remarkable and uniform neurologic manifestations. C57BL/6 owned the highest susceptibility and pathogenicity to the nervous system, referred to as movement disorders, with 100% incidence, while KM was an economic model for a Chinese study characterized by lower limb weakness with 62% morbidity. Slight yellow extraocular exudates were observed in BALB/c, suggesting the association with similar ocular findings to those of clinical cases. The virus distribution and pathological changes in the sera, brains, livers, kidneys, spleens, and testes during disease progression had strong regularity and uniformity, demonstrating the effectiveness and plasticity of the animal models. The successful establishment of these animal models will be conducive to expound the pathogenic mechanism of GBS. Full article

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