Viruses

797 KiB

Open AccessArticle

Localization, Concentration, and Transmission Efficiency of Banana bunchy top virus in Four Asexual Lineages of Pentalonia aphids

by Shizu Watanabe, April M. Greenwell and Alberto Bressan

Viruses 2013, 5(2), 758-776; https://doi.org/10.3390/v5020758 - 22 Feb 2013

Cited by 50 | Viewed by 9698

Abstract

Banana bunchy top virus (BBTV) is the most destructive pathogenic virus of banana plants worldwide. The virus is transmitted in a circulative non-propagative manner by the banana aphid, Pentalonia nigronervosa Coquerel. In this work, we examined the localization, accumulation, and transmission efficiency of [...] Read more.

Banana bunchy top virus (BBTV) is the most destructive pathogenic virus of banana plants worldwide. The virus is transmitted in a circulative non-propagative manner by the banana aphid, Pentalonia nigronervosa Coquerel. In this work, we examined the localization, accumulation, and transmission efficiency of BBTV in four laboratory-established lineages of Pentalonia aphids derived from four different host plants: taro (Colocasia esculenta), heliconia (Heliconia spp.), red ginger (Alpinia purpurata), and banana (Musa sp.). Mitochondrial sequencing identified three and one lineages as Pentalonia caladii van der Goot, a recently proposed species, and P. nigronervosa, respectively. Microsatellite analysis separated the aphid lineages into four distinct genotypes. The transmission of BBTV was tested using leaf disk and whole-plant assays, both of which showed that all four lineages are competent vectors of BBTV, although the P. caladii from heliconia transmitted BBTV to the leaf disks at a significantly lower rate than did P. nigronervosa. The concentration of BBTV in dissected guts, haemolymph, and salivary glands was quantified by real-time PCR. The BBTV titer reached similar concentrations in the guts, haemolymph, and salivary glands of aphids from all four lineages tested. Furthermore, immunofluorescence assays showed that BBTV antigens localized to the anterior midguts and the principal salivary glands, demonstrating a similar pattern of translocations across the four lineages. The results reported in this study showed for the first time that P. caladii is a competent vector of BBTV. Full article

(This article belongs to the Special Issue Plant Viruses)

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164 KiB

Open AccessOpinion

Is a Pacific Coexistence Between Virus and Host the Unexploited Path That May Lead to an HIV Functional Cure?

by Jonathan Fior

Viruses 2013, 5(2), 753-757; https://doi.org/10.3390/v5020753 - 21 Feb 2013

Cited by 3 | Viewed by 7340

Abstract

The SupT1 cell line supports optimal HIV-1 replication, and prolonged in vitro replication in SupT1 cells renders the virus significantly less virulent. This raises the question of whether the infusion of SupT1 cells could be used as a cell-based therapy to induce a [...] Read more.

The SupT1 cell line supports optimal HIV-1 replication, and prolonged in vitro replication in SupT1 cells renders the virus significantly less virulent. This raises the question of whether the infusion of SupT1 cells could be used as a cell-based therapy to induce a pacific coexistence between the HIV virus and its human host. In a recent study, I investigated this potential therapeutic strategy in vitro. The results suggested that this approach should be further explored in HIV-susceptible animal models. Such studies may lead to the development of a functional cure for HIV infection. Full article

(This article belongs to the Special Issue AIDS Vaccine 2014)

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Open AccessReview

Intrathecal Humoral Immunity to Encephalitic RNA Viruses

by Timothy W. Phares, Stephen A. Stohlman and Cornelia C. Bergmann

Viruses 2013, 5(2), 732-752; https://doi.org/10.3390/v5020732 - 15 Feb 2013

Cited by 22 | Viewed by 7491

Abstract

The nervous system is the target for acute encephalitic viral infections, as well as a reservoir for persisting viruses. Intrathecal antibody (Ab) synthesis is well documented in humans afflicted by infections associated with neurological complications, as well as the demyelinating disease, multiple sclerosis. [...] Read more.

The nervous system is the target for acute encephalitic viral infections, as well as a reservoir for persisting viruses. Intrathecal antibody (Ab) synthesis is well documented in humans afflicted by infections associated with neurological complications, as well as the demyelinating disease, multiple sclerosis. This review focuses on the origin, recruitment, maintenance, and biological relevance of Ab-secreting cells (ASC) found in the central nervous system (CNS) following experimental neurotropic RNA virus infections. We will summarize evidence for a highly dynamic, evolving humoral response characterized by temporal alterations in B cell subsets, proliferation, and differentiation. Overall local Ab plays a beneficial role via complement-independent control of virus replication, although cross or self-reactive Ab to CNS antigens may contribute to immune-mediated pathogenesis during some infections. Importantly, protective Ab exert anti-viral activity not only by direct neutralization, but also by binding to cell surface-expressed viral glycoproteins. Ab engagement of viral glycoproteins blocks budding and mediates intracellular signaling leading to restored homeostatic and innate functions. The sustained Ab production by local ASC, as well as chemokines and cytokines associated with ASC recruitment and retention, are highlighted as critical components of immune control. Full article

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604 KiB

Open AccessReview

Oxidative Stress and HPV Carcinogenesis

by Federico De Marco

Viruses 2013, 5(2), 708-731; https://doi.org/10.3390/v5020708 - 12 Feb 2013

Cited by 99 | Viewed by 9771

Abstract

Extensive experimental work has conclusively demonstrated that infection with certain types of human papillomaviruses, the so-called high-risk human papillomavirus (HR-HPV), represent a most powerful human carcinogen. However, neoplastic growth is a rare and inappropriate outcome in the natural history of HPV, and a [...] Read more.

Extensive experimental work has conclusively demonstrated that infection with certain types of human papillomaviruses, the so-called high-risk human papillomavirus (HR-HPV), represent a most powerful human carcinogen. However, neoplastic growth is a rare and inappropriate outcome in the natural history of HPV, and a number of other events have to concur in order to induce the viral infection into the (very rare) neoplastic transformation. From this perspective, a number of putative viral, host, and environmental co-factors have been proposed as potential candidates. Among them oxidative stress (OS) is an interesting candidate, yet comparatively underexplored. OS is a constant threat to aerobic organisms being generated during mitochondrial oxidative phosphorylation, as well as during inflammation, infections, ionizing irradiation, UV exposure, mechanical and chemical stresses. Epithelial tissues, the elective target for HPV infection, are heavily exposed to all named sources of OS. Two different types of cooperative mechanisms are presumed to occur between OS and HPV: I) The OS genotoxic activity and the HPV-induced genomic instability concur independently to the generation of the molecular damage necessary for the emergence of neoplastic clones. This first mode is merely a particular form of co-carcinogenesis; and II) OS specifically interacts with one or more molecular stages of neoplastic initiation and/or progression induced by the HPV infection. This manuscript was designed to summarize available data on this latter hypothesis. Experimental data and indirect evidences on promoting the activity of OS in viral infection and viral integration will be reviewed. The anti-apoptotic and pro-angiogenetic role of NO (nitric oxide) and iNOS (inducible nitric oxide synthase) will be discussed together with the OS/HPV cooperation in inducing cancer metabolism adaptation. Unexplored/underexplored aspects of the OS interplay with the HPV-driven carcinogenesis will be highlighted. The aim of this paper is to stimulate new areas of study and innovative approaches. Full article

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Open AccessReview

Directional Spread of Alphaherpesviruses in the Nervous System

by Tal Kramer and Lynn W. Enquist

Viruses 2013, 5(2), 678-707; https://doi.org/10.3390/v5020678 - 11 Feb 2013

Cited by 83 | Viewed by 12305

Abstract

Alphaherpesviruses are pathogens that invade the nervous systems of their mammalian hosts. Directional spread of infection in the nervous system is a key component of the viral lifecycle and is critical for the onset of alphaherpesvirus-related diseases. Many alphaherpesvirus infections originate at peripheral [...] Read more.

Alphaherpesviruses are pathogens that invade the nervous systems of their mammalian hosts. Directional spread of infection in the nervous system is a key component of the viral lifecycle and is critical for the onset of alphaherpesvirus-related diseases. Many alphaherpesvirus infections originate at peripheral sites, such as epithelial tissues, and then enter neurons of the peripheral nervous system (PNS), where lifelong latency is established. Following reactivation from latency and assembly of new viral particles, the infection typically spreads back out towards the periphery. These spread events result in the characteristic lesions (cold sores) commonly associated with herpes simplex virus (HSV) and herpes zoster (shingles) associated with varicella zoster virus (VZV). Occasionally, the infection spreads transsynaptically from the PNS into higher order neurons of the central nervous system (CNS). Spread of infection into the CNS, while rarer in natural hosts, often results in severe consequences, including death. In this review, we discuss the viral and cellular mechanisms that govern directional spread of infection in the nervous system. We focus on the molecular events that mediate long distance directional transport of viral particles in neurons during entry and egress. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessArticle

Predicted Peptides from Non-Structural Proteins of Porcine Reproductive and Respiratory Syndrome Virus Are Able to Induce IFN-γ and IL-10

by Alexel Burgara-Estrella, Ivan Díaz, Irene M. Rodríguez-Gómez, Sabine E. Essler, Jesús Hernández and Enric Mateu

Viruses 2013, 5(2), 663-677; https://doi.org/10.3390/v5020663 - 11 Feb 2013

Cited by 37 | Viewed by 6296

Abstract

This work describes peptides from non-structural proteins (nsp) of porcine reproductive and respiratory syndrome virus (PRRSV) predicted as potential T cell epitopes by bioinfornatics and tested for their ability to induce IFN-γ and IL-10 responses. Pigs immunized with either genotype 1 or genotype [...] Read more.

This work describes peptides from non-structural proteins (nsp) of porcine reproductive and respiratory syndrome virus (PRRSV) predicted as potential T cell epitopes by bioinfornatics and tested for their ability to induce IFN-γ and IL-10 responses. Pigs immunized with either genotype 1 or genotype 2 PRRSV attenuated vaccines (n=5/group) and unvaccinated pigs (n = 4) were used to test the peptides. Swine leukocyte antigen haplotype of each pig was also determined. Pigs were initially screened for IFN-γ responses (ELISPOT) and three peptides were identified; two of them in non-conserved segments of nsp2 and nsp5 and the other in a conserved region of nsp5 peptide. Then, peptides were screened for IL-10 inducing properties. Six peptides were found to induce IL-10 release in PBMC and some of them were also able to inhibit IFN-γ responses on PHA-stimulated cells. Interestingly, the IFN-γ low responder pigs against PRRSV were mostly homozygous for their SLA haplotypes. In conclusion, these results indicate that nsp of PRRSV contain T-cell epitopes inducing IFN-γ responses as well as IL-10 inducing segments with inhibitory capabilities. Full article

(This article belongs to the Section Animal Viruses)

333 KiB

Open AccessCommunication

Low Copper and High Manganese Levels in Prion Protein Plaques

by Christopher J. Johnson, P.U.P.A. Gilbert, Mike Abrecht, Katherine L. Baldwin, Robin E. Russell, Joel A. Pedersen, Judd M. Aiken and Debbie McKenzie

Viruses 2013, 5(2), 654-662; https://doi.org/10.3390/v5020654 - 11 Feb 2013

Cited by 24 | Viewed by 7008

Abstract

Accumulation of aggregates rich in an abnormally folded form of the prion protein characterize the neurodegeneration caused by transmissible spongiform encephalopathies (TSEs). The molecular triggers of plaque formation and neurodegeneration remain unknown, but analyses of TSE-infected brain homogenates and preparations enriched for abnormal [...] Read more.

Accumulation of aggregates rich in an abnormally folded form of the prion protein characterize the neurodegeneration caused by transmissible spongiform encephalopathies (TSEs). The molecular triggers of plaque formation and neurodegeneration remain unknown, but analyses of TSE-infected brain homogenates and preparations enriched for abnormal prion protein suggest that reduced levels of copper and increased levels of manganese are associated with disease. The objectives of this study were to: (1) assess copper and manganese levels in healthy and TSE-infected Syrian hamster brain homogenates; (2) determine if the distribution of these metals can be mapped in TSE-infected brain tissue using X-ray photoelectron emission microscopy (X-PEEM) with synchrotron radiation; and (3) use X-PEEM to assess the relative amounts of copper and manganese in prion plaques in situ. In agreement with studies of other TSEs and species, we found reduced brain levels of copper and increased levels of manganese associated with disease in our hamster model. We also found that the in situ levels of these metals in brainstem were sufficient to image by X-PEEM. Using immunolabeled prion plaques in directly adjacent tissue sections to identify regions to image by X-PEEM, we found a statistically significant relationship of copper-manganese dysregulation in prion plaques: copper was depleted whereas manganese was enriched. These data provide evidence for prion plaques altering local transition metal distribution in the TSE-infected central nervous system. Full article

(This article belongs to the Special Issue Recent Developments in the Prion Field)

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Open AccessArticle

Phage Lambda P Protein: Trans-Activation, Inhibition Phenotypes and their Suppression

by Sidney Hayes, Craig Erker, Monique A. Horbay, Kristen Marciniuk, Wen Wang and Connie Hayes

Viruses 2013, 5(2), 619-653; https://doi.org/10.3390/v5020619 - 6 Feb 2013

Cited by 9 | Viewed by 7730

Abstract

The initiation of bacteriophage λ replication depends upon interactions between the oriλ DNA site, phage proteins O and P, and E. coli host replication proteins. P exhibits a high affinity for DnaB, the major replicative helicase for unwinding double stranded DNA. The [...] Read more.

The initiation of bacteriophage λ replication depends upon interactions between the oriλ DNA site, phage proteins O and P, and E. coli host replication proteins. P exhibits a high affinity for DnaB, the major replicative helicase for unwinding double stranded DNA. The concept of P-lethality relates to the hypothesis that P can sequester DnaB and in turn prevent cellular replication initiation from oriC. Alternatively, it was suggested that P-lethality does not involve an interaction between P and DnaB, but is targeted to DnaA. P-lethality is assessed by examining host cells for transformation by ColE1-type plasmids that can express P, and the absence of transformants is attributed to a lethal effect of P expression. The plasmid we employed enabled conditional expression of P, where under permissive conditions, cells were efficiently transformed. We observed that ColE1 replication and plasmid establishment upon transformation is extremely sensitive to P, and distinguish this effect from P-lethality directed to cells. We show that alleles of dnaB protect the variant cells from P expression. P-dependent cellular filamentation arose in ΔrecA or lexA[Ind^-] cells, defective for SOS induction. Replication propagation and restart could represent additional targets for P interference of E. coli replication, beyond the oriC-dependent initiation step. Full article

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

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521 KiB

Open AccessReview

Carbohydrate-Related Inhibitors of Dengue Virus Entry

by Kazuya I.P.J. Hidari, Tomoko Abe and Takashi Suzuki

Viruses 2013, 5(2), 605-618; https://doi.org/10.3390/v5020605 - 6 Feb 2013

Cited by 45 | Viewed by 8575

Abstract

Dengue virus (DENV), which is transmitted by Aedes mosquitoes, causes fever and hemorrhagic disorders in humans. The virus entry process mediated through host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue disease. Therefore, elucidation of the molecular mechanisms [...] Read more.

Dengue virus (DENV), which is transmitted by Aedes mosquitoes, causes fever and hemorrhagic disorders in humans. The virus entry process mediated through host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue disease. Therefore, elucidation of the molecular mechanisms underlying virus entry is essential for an understanding of dengue pathology and for the development of effective new anti-dengue agents. DENV binds to its receptor molecules mediated through a viral envelope (E) protein, followed by incorporation of the virus-receptor complex inside cells. The fusion between incorporated virus particles and host endosome membrane under acidic conditions is mediated through the function of DENV E protein. Carbohydrate molecules, such as sulfated glycosaminoglycans (GAG) and glycosphingolipids, and carbohydrate-recognition proteins, termed lectins, inhibit virus entry. This review focuses on carbohydrate-derived entry inhibitors, and also introduces functionally related compounds with similar inhibitory mechanisms against DENV entry. Full article

(This article belongs to the Special Issue Viral Entry Inhibitors)

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568 KiB

Open AccessReview

HIV-1 Diversity in the Envelope Glycoproteins: Implications for Viral Entry Inhibition

by Leonardo Augusto Luvison Araújo and Sabrina E. M. Almeida

Viruses 2013, 5(2), 595-604; https://doi.org/10.3390/v5020595 - 6 Feb 2013

Cited by 25 | Viewed by 6603

Abstract

Entry of HIV-1 into a host cell is a multi-step process, with the viral envelope gp120 and gp41 acting sequentially to mediate the viral attachment, CD4 binding, coreceptor binding, and fusion of the viral and host membranes. The emerging class of antiretroviral agents, [...] Read more.

Entry of HIV-1 into a host cell is a multi-step process, with the viral envelope gp120 and gp41 acting sequentially to mediate the viral attachment, CD4 binding, coreceptor binding, and fusion of the viral and host membranes. The emerging class of antiretroviral agents, collectively known as entry inhibitors, interfere in some of these steps. However, viral diversity has implications for possible differential responses to entry inhibitors, since envelope is the most variable of all HIV genes. Different HIV genetic forms carry in their genomes genetic signatures and polymorphisms that could alter the structure of viral proteins which are targeted by drugs, thus impairing antiretroviral binding and efficacy. This review will examine current research that describes subtype differences in envelope at the genetic level and the effects of mutations on the efficacy of current entry inhibitors. Full article

(This article belongs to the Special Issue Viral Entry Inhibitors)

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Open AccessReview

Respiratory Syncytial Virus: Current Progress in Vaccine Development

by Rajeev Rudraraju, Bart G. Jones, Robert Sealy, Sherri L. Surman and Julia L. Hurwitz

Viruses 2013, 5(2), 577-594; https://doi.org/10.3390/v5020577 - 5 Feb 2013

Cited by 43 | Viewed by 9447

Abstract

Respiratory syncytial virus (RSV) is the etiological agent for a serious lower respiratory tract disease responsible for close to 200,000 annual deaths worldwide. The first infection is generally most severe, while re-infections usually associate with a milder disease. This observation and the finding [...] Read more.

Respiratory syncytial virus (RSV) is the etiological agent for a serious lower respiratory tract disease responsible for close to 200,000 annual deaths worldwide. The first infection is generally most severe, while re-infections usually associate with a milder disease. This observation and the finding that re-infection risks are inversely associated with neutralizing antibody titers suggest that immune responses generated toward a first RSV exposure can significantly reduce morbidity and mortality throughout life. For more than half a century, researchers have endeavored to design a vaccine for RSV that can mimic or improve upon natural protective immunity without adverse events. The virus is herein described together with the hurdles that must be overcome to develop a vaccine and some current vaccine development approaches. Full article

(This article belongs to the Special Issue Pneumoviruses and Metapneumoviruses)

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Open AccessArticle

Identifying the Viral Genes Encoding Envelope Glycoproteins for Differentiation of Cyprinid herpesvirus 3 Isolates

by Jee Eun Han, Ji Hyung Kim, Tristan Renault, Casiano Choresca Jr., Sang Phil Shin, Jin Woo Jun and Se Chang Park

Viruses 2013, 5(2), 568-576; https://doi.org/10.3390/v5020568 - 31 Jan 2013

Cited by 10 | Viewed by 6343

Abstract

Cyprinid herpes virus 3 (CyHV-3) diseases have been reported around the world and are associated with high mortalities of koi (Cyprinus carpio). Although little work has been conducted on the molecular analysis of this virus, glycoprotein genes identified in [...] Read more.

Cyprinid herpes virus 3 (CyHV-3) diseases have been reported around the world and are associated with high mortalities of koi (Cyprinus carpio). Although little work has been conducted on the molecular analysis of this virus, glycoprotein genes identified in the present study seem to be valuable targets for genetic comparison of this virus. Three envelope glycoprotein genes (ORF25, 65 and 116) of the CyHV-3 isolates from the USA, Israel, Japan and Korea were compared, and interestingly, sequence insertions or deletions were observed in these target regions. In addition, polymorphisms were presented in microsatellite zones from two glycoprotein genes (ORF65 and 116). In phylogenetic tree analysis, the Korean isolate was remarkably distinguished from USA, Israel, Japan isolates. These findings may be suitable for many applications including isolates differentiation and phylogeny studies. Full article

(This article belongs to the Section Animal Viruses)

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554 KiB

Open AccessArticle

Genetic Diversity of Spike, 3a, 3b and E Genes of Infectious Bronchitis Viruses and Emergence of New Recombinants in Korea

by Mei-Lan Mo, Seung-Min Hong, Hyuk-Joon Kwon, Il-Hwan Kim, Chang-Seon Song and Jae-Hong Kim

Viruses 2013, 5(2), 550-567; https://doi.org/10.3390/v5020550 - 31 Jan 2013

Cited by 23 | Viewed by 7207

Abstract

The nucleotide sequences of a region including S1, S2, 3a, 3b and E genes of twenty-seven infectious bronchitis virus (IBV) isolates in Korea between 1990–2011 were determined and phylogenetic and computational recombination analyses were conducted. The sizes of coding regions of some genes [...] Read more.

The nucleotide sequences of a region including S1, S2, 3a, 3b and E genes of twenty-seven infectious bronchitis virus (IBV) isolates in Korea between 1990–2011 were determined and phylogenetic and computational recombination analyses were conducted. The sizes of coding regions of some genes varied among IBV isolates due to deletion or insertion of nucleotides; the nucleotide similarities of S1, S2, 3a, 3b and E genes among the 27 isolates were 75.9%–100.0%, 85%–100.0%, 64.0%–100.0%, 60.4%–100.0% and 83.1%–100.0%, respectively. According to phylogenetic analysis of S1 gene, the 27 isolates were divided into five genotypes, Mass, Korean-I (K-I), QX-like, KM91-like and New cluster 1. The phylogenetic trees based on the S2, 3a, 3b, E genes and S1-S2-3a-3b-E (S1-E) region nucleotide sequences did not closely follow the clustering based on the S1 sequence. The New cluster 1 prevalent during 2009 and 2010 was not found in 2011 but QX-like viruses became prevalent in 2011. The recombination analysis revealed two new S gene recombinants, 11036 and 11052 which might have been derived from recombinations between the New cluster 1 and QX-like viruses and between the K-I and H120 (vaccine) viruses, respectively. In conclusion, multiple IBV genotypes have co-circulated; QX-like viruses have recurred and new recombinants have emerged in Korea. This has enriched molecular epidemiology information of IBV and is useful for the control of IB in Korea. Full article

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Open AccessReview

Arenavirus Budding: A Common Pathway with Mechanistic Differences

by Svenja Wolff, Hideki Ebihara and Allison Groseth

Viruses 2013, 5(2), 528-549; https://doi.org/10.3390/v5020528 - 31 Jan 2013

Cited by 26 | Viewed by 9666

Abstract

The Arenaviridae is a diverse and growing family of viruses that includes several agents responsible for important human diseases. Despite the importance of this family for public health, particularly in Africa and South America, much of its biology remains poorly understood. However, in [...] Read more.

The Arenaviridae is a diverse and growing family of viruses that includes several agents responsible for important human diseases. Despite the importance of this family for public health, particularly in Africa and South America, much of its biology remains poorly understood. However, in recent years significant progress has been made in this regard, particularly relating to the formation and release of new enveloped virions, which is an essential step in the viral lifecycle. While this process is mediated chiefly by the viral matrix protein Z, recent evidence suggests that for some viruses the nucleoprotein (NP) is also required to enhance the budding process. Here we highlight and compare the distinct budding mechanisms of different arenaviruses, concentrating on the role of the matrix protein Z, its known late domain sequences, and the involvement of cellular endosomal sorting complex required for transport (ESCRT) pathway components. Finally we address the recently described roles for the nucleoprotein NP in budding and ribonucleoprotein complex (RNP) incorporation, as well as discussing possible mechanisms related to its involvement. Full article

(This article belongs to the Special Issue Arenaviruses)

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Open AccessReview

Learning from the Messengers: Innate Sensing of Viruses and Cytokine Regulation of Immunity — Clues for Treatments and Vaccines

by Jesper Melchjorsen

Viruses 2013, 5(2), 470-527; https://doi.org/10.3390/v5020470 - 31 Jan 2013

Cited by 41 | Viewed by 15476

Abstract

Virus infections are a major global public health concern, and only via substantial knowledge of virus pathogenesis and antiviral immune responses can we develop and improve medical treatments, and preventive and therapeutic vaccines. Innate immunity and the shaping of efficient early immune responses [...] Read more.

Virus infections are a major global public health concern, and only via substantial knowledge of virus pathogenesis and antiviral immune responses can we develop and improve medical treatments, and preventive and therapeutic vaccines. Innate immunity and the shaping of efficient early immune responses are essential for control of viral infections. In order to trigger an efficient antiviral defense, the host senses the invading microbe via pattern recognition receptors (PRRs), recognizing distinct conserved pathogen-associated molecular patterns (PAMPs). The innate sensing of the invading virus results in intracellular signal transduction and subsequent production of interferons (IFNs) and proinflammatory cytokines. Cytokines, including IFNs and chemokines, are vital molecules of antiviral defense regulating cell activation, differentiation of cells, and, not least, exerting direct antiviral effects. Cytokines shape and modulate the immune response and IFNs are principle antiviral mediators initiating antiviral response through induction of antiviral proteins. In the present review, I describe and discuss the current knowledge on early virus–host interactions, focusing on early recognition of virus infection and the resulting expression of type I and type III IFNs, proinflammatory cytokines, and intracellular antiviral mediators. In addition, the review elucidates how targeted stimulation of innate sensors, such as toll-like receptors (TLRs) and intracellular RNA and DNA sensors, may be used therapeutically. Moreover, I present and discuss data showing how current antimicrobial therapies, including antibiotics and antiviral medication, may interfere with, or improve, immune response. Full article

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Open AccessReview

HCV and Oxidative Stress in the Liver

by Alexander V. Ivanov, Birke Bartosch, Olga A. Smirnova, Maria G. Isaguliants and Sergey N. Kochetkov

Viruses 2013, 5(2), 439-469; https://doi.org/10.3390/v5020439 - 28 Jan 2013

Cited by 170 | Viewed by 15158

Abstract

Hepatitis C virus (HCV) is the etiological agent accounting for chronic liver disease in approximately 2–3% of the population worldwide. HCV infection often leads to liver fibrosis and cirrhosis, various metabolic alterations including steatosis, insulin and interferon resistance or iron overload, and development [...] Read more.

Hepatitis C virus (HCV) is the etiological agent accounting for chronic liver disease in approximately 2–3% of the population worldwide. HCV infection often leads to liver fibrosis and cirrhosis, various metabolic alterations including steatosis, insulin and interferon resistance or iron overload, and development of hepatocellular carcinoma or non-Hodgkin lymphoma. Multiple molecular mechanisms that trigger the emergence and development of each of these pathogenic processes have been identified so far. One of these involves marked induction of a reactive oxygen species (ROS) in infected cells leading to oxidative stress. To date, markers of oxidative stress were observed both in chronic hepatitis C patients and in various in vitro systems, including replicons or stable cell lines expressing viral proteins. The search for ROS sources in HCV-infected cells revealed several mechanisms of ROS production and thus a number of cellular proteins have become targets for future studies. Furthermore, during last several years it has been shown that HCV modifies antioxidant defense mechanisms. The aim of this review is to summarize the present state of art in the field and to try to predict directions for future studies. Full article

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Open AccessReview

Is there a Role for Cyclophilin Inhibitors in the Management of Primary Biliary Cirrhosis?

by Shawn T. Wasilenko, Aldo J. Montano-Loza and Andrew L. Mason

Viruses 2013, 5(2), 423-438; https://doi.org/10.3390/v5020423 - 24 Jan 2013

Cited by 10 | Viewed by 6826

Abstract

Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are poorly understood autoimmune liver diseases. Immunosuppression is used to treat AIH and ursodeoxycholic acid is used to slow the progression of PBC. Nevertheless, a proportion of patients with both disorders progress to liver failure. [...] Read more.

Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are poorly understood autoimmune liver diseases. Immunosuppression is used to treat AIH and ursodeoxycholic acid is used to slow the progression of PBC. Nevertheless, a proportion of patients with both disorders progress to liver failure. Following liver transplantation, up to a third of patients with PBC experience recurrent disease. Moreover a syndrome referred to as “de novo AIH” occurs in a proportion of patients regardless of maintenance immunosuppression, who have been transplanted for disorders unrelated to AIH. Of note, the use of cyclosporine A appears to protect against the development of recurrent PBC and de novo AIH even though it is a less potent immunosuppressive compared to tacrolimus. The reason why cyclosporine A is protective has not been determined. However, a virus resembling mouse mammary tumor virus (MMTV) has been characterized in patients with PBC and AIH. Accordingly, we hypothesized that the protective effect of cyclosporine A in liver transplant recipients may be mediated by the antiviral activity of this cyclophilin inhibitor. Treatment of the MMTV producing MM5MT cells with different antivirals and immunosuppressive agents showed that both cyclosporine A and the analogue NIM811 inhibited MMTV production from the producer cells. Herein, we discuss the evidence supporting the role of MMTV-like human betaretrovirus in the development of PBC and de novo AIH and speculate on the possibility that the agent may be associated with disease following transplantation. We also review the mechanisms of how both cyclosporine A and NIM811 may inhibit betaretrovirus production in vitro. Full article

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

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Viruses, Volume 5, Issue 2 (February 2013) – 17 articles , Pages 423-776

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