Viruses

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Open AccessReview

Virus Escape and Manipulation of Cellular Nonsense-Mediated mRNA Decay

by Giuseppe Balistreri, Claudia Bognanni and Oliver Mühlemann

Viruses 2017, 9(1), 24; https://doi.org/10.3390/v9010024 - 23 Jan 2017

Cited by 48 | Viewed by 9021

Nonsense-mediated mRNA decay (NMD), a cellular RNA turnover pathway targeting RNAs with features resulting in aberrant translation termination, has recently been found to restrict the replication of positive-stranded RNA ((+)RNA) viruses. As for every other antiviral immune system, there is also evidence of [...] Read more.

Nonsense-mediated mRNA decay (NMD), a cellular RNA turnover pathway targeting RNAs with features resulting in aberrant translation termination, has recently been found to restrict the replication of positive-stranded RNA ((+)RNA) viruses. As for every other antiviral immune system, there is also evidence of viruses interfering with and modulating NMD to their own advantage. This review will discuss our current understanding of why and how NMD targets viral RNAs, and elaborate counter-defense strategies viruses utilize to escape NMD. Full article

(This article belongs to the Special Issue Viral Interactions with Host RNA Decay Pathways)

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Open AccessArticle

Feline Panleucopenia Virus NS2 Suppresses the Host IFN-β Induction by Disrupting the Interaction between TBK1 and STING

by Hongtao Kang, Dafei Liu, Jin Tian, Xiaoliang Hu, Xiaozhan Zhang, Hang Yin, Hongxia Wu, Chunguo Liu, Dongchun Guo, Zhijie Li, Qian Jiang, Jiasen Liu and Liandong Qu

Viruses 2017, 9(1), 23; https://doi.org/10.3390/v9010023 - 23 Jan 2017

Cited by 13 | Viewed by 6461

Abstract

Feline panleucopenia virus (FPV) is a highly infectious pathogen that causes severe diseases in pets, economically important animals and wildlife in China. Although FPV was identified several years ago, little is known about how it overcomes the host innate immunity. In the present [...] Read more.

Feline panleucopenia virus (FPV) is a highly infectious pathogen that causes severe diseases in pets, economically important animals and wildlife in China. Although FPV was identified several years ago, little is known about how it overcomes the host innate immunity. In the present study, we demonstrated that infection with the FPV strain Philips-Roxane failed to activate the interferon β (IFN-β) pathway but could antagonize the induction of IFN stimulated by Sendai virus (SeV) in F81 cells. Subsequently, by screening FPV nonstructural and structural proteins, we found that only nonstructural protein 2 (NS2) significantly suppressed IFN expression. We demonstrated that the inhibition of SeV-induced IFN-β production by FPV NS2 depended on the obstruction of the IFN regulatory factor 3 (IRF3) signaling pathway. Further, we verified that NS2 was able to target the serine/threonine-protein kinase TBK1 and prevent it from being recruited by stimulator of interferon genes (STING) protein, which disrupted the phosphorylation of the downstream protein IRF3. Finally, we identified that the C-terminus plus the coiled coil domain are the key domains of NS2 that are required for inhibiting the IFN pathway. Our study has yielded strong evidence for the FPV mechanisms that counteract the host innate immunity. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessReview

Astrovirus Pathogenesis

by Cydney Johnson, Virginia Hargest, Valerie Cortez, Victoria A. Meliopoulos and Stacey Schultz-Cherry

Viruses 2017, 9(1), 22; https://doi.org/10.3390/v9010022 - 22 Jan 2017

Cited by 79 | Viewed by 13540

Abstract

Astroviruses are a major cause of diarrhea in the young, elderly, and the immunocompromised. Since the discovery of human astrovirus type 1 (HAstV-1) in 1975, the family Astroviridae has expanded to include two more human clades and numerous mammalian and avian-specific genotypes. Despite [...] Read more.

Astroviruses are a major cause of diarrhea in the young, elderly, and the immunocompromised. Since the discovery of human astrovirus type 1 (HAstV-1) in 1975, the family Astroviridae has expanded to include two more human clades and numerous mammalian and avian-specific genotypes. Despite this, there is still little known about pathogenesis. The following review highlights the current knowledge of astrovirus pathogenesis, and outlines the critical steps needed to further astrovirus research, including the development of animal models of cell culture systems. Full article

(This article belongs to the Special Issue Astroviruses)

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Open AccessReview

Nuclear Import of Hepatitis B Virus Capsids and Genome

by Lara Gallucci and Michael Kann

Viruses 2017, 9(1), 21; https://doi.org/10.3390/v9010021 - 21 Jan 2017

Cited by 53 | Viewed by 11490

Abstract

Hepatitis B virus (HBV) is an enveloped pararetrovirus with a DNA genome, which is found in an up to 36 nm-measuring capsid. Replication of the genome occurs via an RNA intermediate, which is synthesized in the nucleus. The virus must have thus ways [...] Read more.

Hepatitis B virus (HBV) is an enveloped pararetrovirus with a DNA genome, which is found in an up to 36 nm-measuring capsid. Replication of the genome occurs via an RNA intermediate, which is synthesized in the nucleus. The virus must have thus ways of transporting its DNA genome into this compartment. This review summarizes the data on hepatitis B virus genome transport and correlates the finding to those from other viruses. Full article

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

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Open AccessArticle

Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain

by Jian Yang, Huiqiang Yang, Zhushi Li, Wei Wang, Hua Lin, Lina Liu, Qianzhi Ni, Xinyu Liu, Xianwu Zeng, Yonglin Wu and Yuhua Li

Viruses 2017, 9(1), 20; https://doi.org/10.3390/v9010020 - 21 Jan 2017

Cited by 36 | Viewed by 6045

Abstract

The attenuated Japanese encephalitis virus (JEV) strain SA14-14-2 has been successfully utilized to prevent JEV infection; however, the attenuation determinants have not been fully elucidated. The envelope (E) protein of the attenuated JEV SA14-14-2 strain differs from that of the virulent parental SA14 [...] Read more.

The attenuated Japanese encephalitis virus (JEV) strain SA14-14-2 has been successfully utilized to prevent JEV infection; however, the attenuation determinants have not been fully elucidated. The envelope (E) protein of the attenuated JEV SA14-14-2 strain differs from that of the virulent parental SA14 strain at eight amino acid positions (E107, E138, E176, E177, E264, E279, E315, and E439). Here, we investigated the SA14-14-2-attenuation determinants by mutating E107, E138, E176, E177, and E279 in SA14-14-2 to their status in the parental virulent strain and tested the replication capacity, neurovirulence, neuroinvasiveness, and mortality associated with the mutated viruses in mice, as compared with those of JEV SA14-14-2 and SA14. Our findings indicated that revertant mutations at the E138 or E107 position significantly increased SA14-14-2 virulence, whereas other revertant mutations exhibited significant increases in neurovirulence only when combined with E138, E107, and other mutations. Revertant mutations at all eight positions in the E protein resulted in the highest degree of SA14-14-2 virulence, although this was still lower than that observed in SA14. These results demonstrated the critical role of the viral E protein in controlling JEV virulence and identified the amino acids at the E107 and E138 positions as the key determinants of SA14-14-2 neurovirulence. Full article

(This article belongs to the Special Issue Advances in Flavivirus Research)

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Open AccessArticle

Novel Approach for Isolation and Identification of Porcine Epidemic Diarrhea Virus (PEDV) Strain NJ Using Porcine Intestinal Epithelial Cells

by Wen Shi, Shuo Jia, Haiyuan Zhao, Jiyuan Yin, Xiaona Wang, Meiling Yu, Sunting Ma, Yang Wu, Ying Chen, Wenlu Fan, Yigang Xu and Yijing Li

Viruses 2017, 9(1), 19; https://doi.org/10.3390/v9010019 - 21 Jan 2017

Cited by 22 | Viewed by 8506

Abstract

Porcine epidemic diarrhea virus (PEDV), which is the causative agent of porcine epidemic diarrhea in China and other countries, is responsible for serious economic losses in the pork industry. Inactivated PEDV vaccine plays a key role in controlling the prevalence of PEDV. However, [...] Read more.

Porcine epidemic diarrhea virus (PEDV), which is the causative agent of porcine epidemic diarrhea in China and other countries, is responsible for serious economic losses in the pork industry. Inactivated PEDV vaccine plays a key role in controlling the prevalence of PEDV. However, consistently low viral titers are obtained during the propagation of PEDV in vitro; this represents a challenge to molecular analyses of the virus and vaccine development. In this study, we successfully isolated a PEDV isolate (strain NJ) from clinical samples collected during a recent outbreak of diarrhea in piglets in China, using porcine intestinal epithelial cells (IEC). We found that the isolate was better adapted to growth in IECs than in Vero cells, and the titer of the IEC cultures was 10^4.5 TCID₅₀/0.1 mL at passage 45. Mutations in the S protein increased with the viral passage and the mutations tended towards attenuation. Viral challenge showed that the survival of IEC-adapted cultures was higher at the 45th passage than at the 5th passage. The use of IECs to isolate and propagate PEDV provides an effective approach for laboratory-based diagnosis of PEDV, as well as studies of the epidemiological characteristics and molecular biology of this virus. Full article

(This article belongs to the Special Issue Porcine Viruses)

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Open AccessReview

Control of Hepatitis B Virus by Cytokines

by Yuchen Xia and Ulrike Protzer

Viruses 2017, 9(1), 18; https://doi.org/10.3390/v9010018 - 20 Jan 2017

Cited by 99 | Viewed by 8857

Abstract

Hepatitis B virus (HBV) infection remains a major public health problem worldwide with more than 240 million individuals chronically infected. Current treatments can control HBV replication to a large extent, but cannot eliminate HBV infection. Cytokines have been shown to control HBV replication [...] Read more.

Hepatitis B virus (HBV) infection remains a major public health problem worldwide with more than 240 million individuals chronically infected. Current treatments can control HBV replication to a large extent, but cannot eliminate HBV infection. Cytokines have been shown to control HBV replication and contribute to HBV cure in different models. Cytokines play an important role in limiting acute HBV infection in patients and mediate a non-cytolytic clearance of the virus. In this review, we summarize the effects of cytokines and cytokine-induced cellular signaling pathways on different steps of the HBV life cycle, and discuss possible strategies that may contribute to the eradication of HBV through innate immune activation. Full article

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

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Open AccessArticle

A Glimpse of Nucleo-Cytoplasmic Large DNA Virus Biodiversity through the Eukaryotic Genomics Window

by Lucie Gallot-Lavallée and Guillaume Blanc

Viruses 2017, 9(1), 17; https://doi.org/10.3390/v9010017 - 20 Jan 2017

Cited by 45 | Viewed by 7653

Abstract

The nucleocytoplasmic large DNA viruses (NCLDV) are a group of extremely complex double-stranded DNA viruses, which are major parasites of a variety of eukaryotes. Recent studies showed that certain eukaryotes contain fragments of NCLDV DNA integrated in their genome, when surprisingly many of [...] Read more.

The nucleocytoplasmic large DNA viruses (NCLDV) are a group of extremely complex double-stranded DNA viruses, which are major parasites of a variety of eukaryotes. Recent studies showed that certain eukaryotes contain fragments of NCLDV DNA integrated in their genome, when surprisingly many of these organisms were not previously shown to be infected by NCLDVs. We performed an update survey of NCLDV genes hidden in eukaryotic sequences to measure the incidence of this phenomenon in common public sequence databases. A total of 66 eukaryotic genomic or transcriptomic datasets—many of which are from algae and aquatic protists—contained at least one of the five most consistently conserved NCLDV core genes. Phylogenetic study of the eukaryotic NCLDV-like sequences identified putative new members of already recognized viral families, as well as members of as yet unknown viral clades. Genomic evidence suggested that most of these sequences resulted from viral DNA integrations rather than contaminating viruses. Furthermore, the nature of the inserted viral genes helped predicting original functional capacities of the donor viruses. These insights confirm that genomic insertions of NCLDV DNA are common in eukaryotes and can be exploited to delineate the contours of NCLDV biodiversity. Full article

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

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Open AccessReview

Promoter Motifs in NCLDVs: An Evolutionary Perspective

by Graziele Pereira Oliveira, Ana Cláudia dos Santos Pereira Andrade, Rodrigo Araújo Lima Rodrigues, Thalita Souza Arantes, Paulo Victor Miranda Boratto, Ludmila Karen dos Santos Silva, Fábio Pio Dornas, Giliane De Souza Trindade, Betânia Paiva Drumond, Bernard La Scola, Erna Geessien Kroon and Jônatas Santos Abrahão

Viruses 2017, 9(1), 16; https://doi.org/10.3390/v9010016 - 20 Jan 2017

Cited by 18 | Viewed by 9975

Abstract

For many years, gene expression in the three cellular domains has been studied in an attempt to discover sequences associated with the regulation of the transcription process. Some specific transcriptional features were described in viruses, although few studies have been devoted to understanding [...] Read more.

For many years, gene expression in the three cellular domains has been studied in an attempt to discover sequences associated with the regulation of the transcription process. Some specific transcriptional features were described in viruses, although few studies have been devoted to understanding the evolutionary aspects related to the spread of promoter motifs through related viral families. The discovery of giant viruses and the proposition of the new viral order Megavirales that comprise a monophyletic group, named nucleo-cytoplasmic large DNA viruses (NCLDV), raised new questions in the field. Some putative promoter sequences have already been described for some NCLDV members, bringing new insights into the evolutionary history of these complex microorganisms. In this review, we summarize the main aspects of the transcription regulation process in the three domains of life, followed by a systematic description of what is currently known about promoter regions in several NCLDVs. We also discuss how the analysis of the promoter sequences could bring new ideas about the giant viruses’ evolution. Finally, considering a possible common ancestor for the NCLDV group, we discussed possible promoters’ evolutionary scenarios and propose the term “MEGA-box” to designate an ancestor promoter motif (‘TATATAAAATTGA’) that could be evolved gradually by nucleotides’ gain and loss and point mutations. Full article

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

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Open AccessReview

The Astrovirus Capsid: A Review

by Carlos F. Arias and Rebecca M. DuBois

Viruses 2017, 9(1), 15; https://doi.org/10.3390/v9010015 - 19 Jan 2017

Cited by 92 | Viewed by 15168

Abstract

Astroviruses are enterically transmitted viruses that cause infections in mammalian and avian species. Astroviruses are nonenveloped, icosahedral viruses comprised of a capsid protein shell and a positive-sense, single-stranded RNA genome. The capsid protein undergoes dramatic proteolytic processing both inside and outside of the [...] Read more.

Astroviruses are enterically transmitted viruses that cause infections in mammalian and avian species. Astroviruses are nonenveloped, icosahedral viruses comprised of a capsid protein shell and a positive-sense, single-stranded RNA genome. The capsid protein undergoes dramatic proteolytic processing both inside and outside of the host cell, resulting in a coordinated maturation process that affects cellular localization, virus structure, and infectivity. After maturation, the capsid protein controls the initial phases of virus infection, including virus attachment, endocytosis, and genome release into the host cell. The astrovirus capsid is the target of host antibodies including virus-neutralizing antibodies. The capsid protein also mediates the binding of host complement proteins and inhibits complement activation. Here, we will review our knowledge on the astrovirus capsid protein (CP), with particular attention to the recent structural, biochemical, and virological studies that have advanced our understanding of the astrovirus life cycle. Full article

(This article belongs to the Special Issue Astroviruses)

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Open AccessReview

The IMPORTance of the Nucleus during Flavivirus Replication

by Adam J. Lopez-Denman and Jason M. Mackenzie

Viruses 2017, 9(1), 14; https://doi.org/10.3390/v9010014 - 19 Jan 2017

Cited by 34 | Viewed by 8064

Abstract

Flaviviruses are a large group of arboviruses of significant medical concern worldwide. With outbreaks a common occurrence, the need for efficient viral control is required more than ever. It is well understood that flaviviruses modulate the composition and structure of membranes in the [...] Read more.

Flaviviruses are a large group of arboviruses of significant medical concern worldwide. With outbreaks a common occurrence, the need for efficient viral control is required more than ever. It is well understood that flaviviruses modulate the composition and structure of membranes in the cytoplasm that are crucial for efficient replication and evading immune detection. As the flavivirus genome consists of positive sense RNA, replication can occur wholly within the cytoplasm. What is becoming more evident is that some viral proteins also have the ability to translocate to the nucleus, with potential roles in replication and immune system perturbation. In this review, we discuss the current understanding of flavivirus nuclear localisation, and the function it has during flavivirus infection. We also describe—while closely related—the functional differences between similar viral proteins in their nuclear translocation. Full article

(This article belongs to the Special Issue Advances in Flavivirus Research)

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Open AccessReview

Adenoviral Vectors Armed with Cell Fusion-Inducing Proteins as Anti-Cancer Agents

by Joshua Del Papa and Robin J. Parks

Viruses 2017, 9(1), 13; https://doi.org/10.3390/v9010013 - 19 Jan 2017

Cited by 8 | Viewed by 5649

Abstract

Cancer is a devastating disease that affects millions of patients every year, and causes an enormous economic burden on the health care system and emotional burden on affected families. The first line of defense against solid tumors is usually extraction of the tumor, [...] Read more.

Cancer is a devastating disease that affects millions of patients every year, and causes an enormous economic burden on the health care system and emotional burden on affected families. The first line of defense against solid tumors is usually extraction of the tumor, when possible, by surgical methods. In cases where solid tumors can not be safely removed, chemotherapy is often the first line of treatment. As metastatic cancers often become vigorously resistant to treatments, the development of novel, more potent and selective anti-cancer strategies is of great importance. Adenovirus (Ad) is the most commonly used virus in cancer clinical trials, however, regardless of the nature of the Ad-based therapeutic, complete responses to treatment remain rare. A number of pre-clinical studies have shown that, for all vector systems, viral spread throughout the tumor mass can be a major limiting factor for complete tumor elimination. By expressing exogenous cell-fusion proteins, many groups have shown improved spread of Ad-based vectors. This review summarizes the research done to examine the potency of Ad vectors expressing fusogenic proteins as anti-cancer therapeutics. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessReview

Perspective on Global Measles Epidemiology and Control and the Role of Novel Vaccination Strategies

by Melissa M. Coughlin, Andrew S. Beck, Bettina Bankamp and Paul A. Rota

Viruses 2017, 9(1), 11; https://doi.org/10.3390/v9010011 - 19 Jan 2017

Cited by 79 | Viewed by 17282

Abstract

Measles is a highly contagious, vaccine preventable disease. Measles results in a systemic illness which causes profound immunosuppression often leading to severe complications. In 2010, the World Health Assembly declared that measles can and should be eradicated. Measles has been eliminated in the [...] Read more.

Measles is a highly contagious, vaccine preventable disease. Measles results in a systemic illness which causes profound immunosuppression often leading to severe complications. In 2010, the World Health Assembly declared that measles can and should be eradicated. Measles has been eliminated in the Region of the Americas, and the remaining five regions of the World Health Organization (WHO) have adopted measles elimination goals. Significant progress has been made through increased global coverage of first and second doses of measles-containing vaccine, leading to a decrease in global incidence of measles, and through improved case based surveillance supported by the WHO Global Measles and Rubella Laboratory Network. Improved vaccine delivery methods will likely play an important role in achieving measles elimination goals as these delivery methods circumvent many of the logistic issues associated with subcutaneous injection. This review highlights the status of global measles epidemiology, novel measles vaccination strategies, and describes the pathway toward measles elimination. Full article

(This article belongs to the Special Issue Recent Progress in Measles Virus Research)

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Open AccessArticle

Frequency and Pathological Phenotype of Bovine Astrovirus CH13/NeuroS1 Infection in Neurologically-Diseased Cattle: Towards Assessment of Causality

by Senija Selimovic-Hamza, Céline L. Boujon, Monika Hilbe, Anna Oevermann and Torsten Seuberlich

Viruses 2017, 9(1), 12; https://doi.org/10.3390/v9010012 - 18 Jan 2017

Cited by 34 | Viewed by 7456

Abstract

Next-generation sequencing (NGS) has opened up the possibility of detecting new viruses in unresolved diseases. Recently, astrovirus brain infections have been identified in neurologically diseased humans and animals by NGS, among them bovine astrovirus (BoAstV) CH13/NeuroS1, which has been found in brain tissues [...] Read more.

Next-generation sequencing (NGS) has opened up the possibility of detecting new viruses in unresolved diseases. Recently, astrovirus brain infections have been identified in neurologically diseased humans and animals by NGS, among them bovine astrovirus (BoAstV) CH13/NeuroS1, which has been found in brain tissues of cattle with non-suppurative encephalitis. Only a few studies are available on neurotropic astroviruses and a causal relationship between BoAstV CH13/NeuroS1 infections and neurological disease has been postulated, but remains unproven. Aiming at making a step forward towards assessing the causality, we collected brain samples of 97 cases of cattle diagnosed with unresolved non-suppurative encephalitis, and analyzed them by in situ hybridization and immunohistochemistry, to determine the frequency and neuropathological distribution of the BoAstV CH13/NeuroS1 and its topographical correlation to the pathology. We detected BoAstV CH13/NeuroS1 RNA or proteins in neurons throughout all parts of the central nervous system (CNS) in 34% of all cases, but none were detected in cattle of the control group. In general, brain lesions had a high correlation with the presence of the virus. These findings show that a substantial proportion of cattle with non-suppurative encephalitis are infected with BoAstV CH13/NeuroS1 and further substantiate the causal relationship between neurological disease and astrovirus infections. Full article

(This article belongs to the Special Issue Astroviruses)

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Open AccessArticle

A Semipersistent Plant Virus Differentially Manipulates Feeding Behaviors of Different Sexes and Biotypes of Its Whitefly Vector

by Shaohua Lu, Jingjing Li, Xueli Wang, Danyang Song, Rune Bai, Yan Shi, Qinsheng Gu, Yen-Wen Kuo, Bryce W. Falk and Fengming Yan

Viruses 2017, 9(1), 4; https://doi.org/10.3390/v9010004 - 13 Jan 2017

Cited by 36 | Viewed by 6584

Abstract

It is known that plant viruses can change the performance of their vectors. However, there have been no reports on whether or how a semipersistent plant virus manipulates the feeding behaviors of its whitefly vectors. Cucurbit chlorotic yellows virus (CCYV) (genus Crinivirus, [...] Read more.

It is known that plant viruses can change the performance of their vectors. However, there have been no reports on whether or how a semipersistent plant virus manipulates the feeding behaviors of its whitefly vectors. Cucurbit chlorotic yellows virus (CCYV) (genus Crinivirus, family Closteroviridae) is an emergent plant virus in many Asian countries and is transmitted specifically by B and Q biotypes of tobacco whitefly, Bemisia tabaci (Gennadius), in a semipersistent manner. In the present study, we used electrical penetration graph (EPG) technique to investigate the effect of CCYV on the feeding behaviors of B. tabaci. The results showed that CCYV altered feeding behaviors of both biotypes and sexes of B. tabaci with different degrees. CCYV had stronger effects on feeding behaviors of Q biotype than those of B biotype, by increasing duration of phloem salivation and sap ingestion, and could differentially manipulate feeding behaviors of males and females in both biotype whiteflies, with more phloem ingestion in Q biotype males and more non-phloem probing in B biotype males than their respective females. With regard to feeding behaviors related to virus transmission, these results indicated that, when carrying CCYV, B. tabaci Q biotype plays more roles than B biotype, and males make greater contribution than females. Full article

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

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Open AccessArticle

Effective Detection of Porcine Cytomegalovirus Using Non-Invasively Taken Samples from Piglets

by Vladimir A. Morozov, Gerd Heinrichs and Joachim Denner

Viruses 2017, 9(1), 9; https://doi.org/10.3390/v9010009 - 12 Jan 2017

Cited by 20 | Viewed by 5650

Abstract

Shortage of human organs forced the development of xenotransplantation using cells, tissues, and organs from pigs. Xenotransplantation may be associated with the transmission of porcine zoonotic microorganisms, among them the porcine cytomegalovirus (PCMV). To prevent virus transmission, pigs have to be screened using [...] Read more.

Shortage of human organs forced the development of xenotransplantation using cells, tissues, and organs from pigs. Xenotransplantation may be associated with the transmission of porcine zoonotic microorganisms, among them the porcine cytomegalovirus (PCMV). To prevent virus transmission, pigs have to be screened using sensitive methods. In order to perform regular follow-ups and further breeding of the animals, samples for testing should be collected by low-invasive or non-invasive methods. Sera, ear biopsies, as well as oral and anal swabs were collected from ten 10-day-old Aachen minipigs (AaMP) and tested for PCMV using sensitive nested polymerase chain reaction (PCR) as well as uniplex and duplex real-time PCR. Porcine cytomegalovirus DNA was detected most frequently in oral and anal swabs. Comparison of duplex and uniplex real-time PCR systems for PCMV detection demonstrated a lower sensitivity of duplex real-time PCR when the copy numbers of the target genes were low (less 200). Therefore, to increase the efficacy of PCMV detection in piglets, early testing of oral and anal swabs by uniplex real-time PCR is recommended. Full article

(This article belongs to the Special Issue Porcine Viruses)

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Open AccessReview

Astrovirus Diagnostics

by Philippe Pérot, Marc Lecuit and Marc Eloit

Viruses 2017, 9(1), 10; https://doi.org/10.3390/v9010010 - 12 Jan 2017

Cited by 36 | Viewed by 8496

Abstract

Various methods exist to detect an astrovirus infection. Current methods include electron microscopy (EM), cell culture, immunoassays, polymerase chain reaction (PCR) and various other molecular approaches that can be applied in the context of diagnostic or in surveillance studies. With the advent of [...] Read more.

Various methods exist to detect an astrovirus infection. Current methods include electron microscopy (EM), cell culture, immunoassays, polymerase chain reaction (PCR) and various other molecular approaches that can be applied in the context of diagnostic or in surveillance studies. With the advent of metagenomics, novel human astrovirus (HAstV) strains have been found in immunocompromised individuals in association with central nervous system (CNS) infections. This work reviews the past and current methods for astrovirus detection and their uses in both research laboratories and for medical diagnostic purposes. Full article

(This article belongs to the Special Issue Astroviruses)

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Open AccessEditorial

Acknowledgement to Reviewers of Viruses in 2016

by Viruses Editorial Office

Viruses 2017, 9(1), 8; https://doi.org/10.3390/v9010008 - 11 Jan 2017

Cited by 2 | Viewed by 5187

Abstract

The editors of Viruses would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...] Full article

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Open AccessCommentary

The New High Resolution Crystal Structure of NS2B-NS3 Protease of Zika Virus

by Syed Lal Badshah, Abdul Naeem and Yahia Mabkhot

Viruses 2017, 9(1), 7; https://doi.org/10.3390/v9010007 - 10 Jan 2017

Cited by 12 | Viewed by 6314

Abstract

Zika virus (ZIKV) is the cause of a significant viral disease affecting humans, which has spread throughout many South American countries and has also become a threat to Southeastern Asia. This commentary discusses the article “Crystal structure of unlinked NS2B-NS3 protease from Zika [...] Read more.

Zika virus (ZIKV) is the cause of a significant viral disease affecting humans, which has spread throughout many South American countries and has also become a threat to Southeastern Asia. This commentary discusses the article “Crystal structure of unlinked NS2B-NS3 protease from Zika virus” published recently in the journal Science by Zhang et al. of Nanyang Technological University, Singapore. They resolved a 1.58 Å resolution structure of the NS2B-NS3 protease of ZIKV and demonstrated how peptide and non-peptide inhibitors interact with this structure, along with the different conformational states that were observed. This protease crystal structure offers new opportunities for the design and development of novel antiviral drugs used for the treatment and control of ZIKV. Full article

(This article belongs to the Special Issue Advances in Flavivirus Research)

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Open AccessArticle

A Point Mutation in a Herpesvirus Co-Determines Neuropathogenicity and Viral Shedding

by Mathias Franz, Laura B. Goodman, Gerlinde R. Van de Walle, Nikolaus Osterrieder and Alex D. Greenwood

Viruses 2017, 9(1), 6; https://doi.org/10.3390/v9010006 - 10 Jan 2017

Cited by 10 | Viewed by 5308

Abstract

A point mutation in the DNA polymerase gene in equine herpesvirus type 1 (EHV-1) is one determinant for the development of neurological disease in horses. Three recently conducted infection experiments using domestic horses and ponies failed to detect statistically significant differences in viral [...] Read more.

A point mutation in the DNA polymerase gene in equine herpesvirus type 1 (EHV-1) is one determinant for the development of neurological disease in horses. Three recently conducted infection experiments using domestic horses and ponies failed to detect statistically significant differences in viral shedding between the neuropathogenic and non-neuropathogenic variants. These results were interpreted as suggesting the absence of a consistent selective advantage of the neuropathogenic variant and therefore appeared to be inconsistent with a systematic increase in the prevalence of neuropathogenic strains. To overcome potential problems of low statistical power related to small group sizes in these infection experiments, we integrated raw data from all three experiments into a single statistical analysis. The results of this combined analysis showed that infection with the neuropathogenic EHV-1 variant led to a statistically significant increase in viral shedding. This finding is consistent with the idea that neuropathogenic strains could have a selective advantage and are therefore systematically increasing in prevalence in domestic horse populations. However, further studies are required to determine whether a selective advantage indeed exists for neuropathogenic strains. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessArticle

Mx Is Not Responsible for the Antiviral Activity of Interferon-α against Japanese Encephalitis Virus

by Jing Zhou, Shi-Qi Wang, Jian-Chao Wei, Xiao-Min Zhang, Zhi-Can Gao, Ke Liu, Zhi-Yong Ma, Pu-Yan Chen and Bin Zhou

Viruses 2017, 9(1), 5; https://doi.org/10.3390/v9010005 - 10 Jan 2017

Cited by 14 | Viewed by 6691

Abstract

Mx proteins are interferon (IFN)-induced dynamin-like GTPases that are present in all vertebrates and inhibit the replication of myriad viruses. However, the role Mx proteins play in IFN-mediated suppression of Japanese encephalitis virus (JEV) infection is unknown. In this study, we set out [...] Read more.

Mx proteins are interferon (IFN)-induced dynamin-like GTPases that are present in all vertebrates and inhibit the replication of myriad viruses. However, the role Mx proteins play in IFN-mediated suppression of Japanese encephalitis virus (JEV) infection is unknown. In this study, we set out to investigate the effects of Mx1 and Mx2 expression on the interferon-α (IFNα) restriction of JEV replication. To evaluate whether the inhibitory activity of IFNα on JEV is dependent on Mx1 or Mx2, we knocked down Mx1 or Mx2 with siRNA in IFNα-treated PK-15 cells and BHK-21 cells, then challenged them with JEV; the production of progeny virus was assessed by plaque assay, RT-qPCR, and Western blotting. Our results demonstrated that depletion of Mx1 or Mx2 did not affect JEV restriction imposed by IFNα, although these two proteins were knocked down 66% and 79%, respectively. Accordingly, expression of exogenous Mx1 or Mx2 did not change the inhibitory activity of IFNα to JEV. In addition, even though virus-induced membranes were damaged by Brefeldin A (BFA), overexpressing porcine Mx1 or Mx2 did not inhibit JEV proliferation. We found that BFA inhibited JEV replication, not maturation, suggesting that BFA could be developed into a novel antiviral reagent. Collectively, our findings demonstrate that IFNα inhibits JEV infection by Mx-independent pathways. Full article

(This article belongs to the Special Issue Advances in Flavivirus Research)

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Open AccessArticle

Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages

by Tapas K. Nayak, Prabhudutta Mamidi, Abhishek Kumar, Laishram Pradeep K. Singh, Subhransu S. Sahoo, Soma Chattopadhyay and Subhasis Chattopadhyay

Viruses 2017, 9(1), 3; https://doi.org/10.3390/v9010003 - 6 Jan 2017

Cited by 43 | Viewed by 9333

Abstract

Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well [...] Read more.

Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6) MHC-I/II and B7.2 (CD86) were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessReview

Attacked from All Sides: RNA Decay in Antiviral Defense

by Jerome M. Molleston and Sara Cherry

Viruses 2017, 9(1), 2; https://doi.org/10.3390/v9010002 - 4 Jan 2017

Cited by 39 | Viewed by 10167

Abstract

The innate immune system has evolved a number of sensors that recognize viral RNA (vRNA) to restrict infection, yet the full spectrum of host-encoded RNA binding proteins that target these foreign RNAs is still unknown. The RNA decay machinery, which uses exonucleases to [...] Read more.

The innate immune system has evolved a number of sensors that recognize viral RNA (vRNA) to restrict infection, yet the full spectrum of host-encoded RNA binding proteins that target these foreign RNAs is still unknown. The RNA decay machinery, which uses exonucleases to degrade aberrant RNAs largely from the 5′ or 3′ end, is increasingly recognized as playing an important role in antiviral defense. The 5′ degradation pathway can directly target viral messenger RNA (mRNA) for degradation, as well as indirectly attenuate replication by limiting specific pools of endogenous RNAs. The 3′ degradation machinery (RNA exosome) is emerging as a downstream effector of a diverse array of vRNA sensors. This review discusses our current understanding of the roles of the RNA decay machinery in controlling viral infection. Full article

(This article belongs to the Special Issue Viral Interactions with Host RNA Decay Pathways)

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Open AccessReview

The Immune Response to Astrovirus Infection

by Shauna A. Marvin

Viruses 2017, 9(1), 1; https://doi.org/10.3390/v9010001 - 30 Dec 2016

Cited by 9 | Viewed by 6004

Abstract

Astroviruses are one of the leading causes of pediatric gastroenteritis worldwide and are clinically importantly pathogens in the elderly and immunocompromised populations. Although the use of cell culture systems and small animal models have enhanced our understanding of astrovirus infection and pathogenesis, little [...] Read more.

Astroviruses are one of the leading causes of pediatric gastroenteritis worldwide and are clinically importantly pathogens in the elderly and immunocompromised populations. Although the use of cell culture systems and small animal models have enhanced our understanding of astrovirus infection and pathogenesis, little is known about the immune response to astrovirus infection. Studies from humans and animals suggest that adaptive immunity is important in restricting classic and novel astrovirus infections, while studies from animal models and cell culture systems suggest that an innate immune system plays a role in limiting astrovirus replication. The relative contribution of each arm of the immune system in restricting astrovirus infection remains unknown. This review summarizes our current understanding of the immune response to astrovirus infection and highlights some of the key questions that stem from these studies. A full understanding of the immune response to astrovirus infection is required to be able to treat and control astrovirus-induced gastroenteritis. Full article

(This article belongs to the Special Issue Astroviruses)

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Viruses, Volume 9, Issue 1 (January 2017) – 24 articles

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