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Viruses, Volume 8, Issue 12 (December 2016) – 19 articles

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1666 KiB  
Review
Use of Cellular Decapping Activators by Positive-Strand RNA Viruses
by Jennifer Jungfleisch, Bernat Blasco-Moreno and Juana Díez
Viruses 2016, 8(12), 340; https://doi.org/10.3390/v8120340 - 21 Dec 2016
Cited by 6 | Viewed by 6057
Abstract
Positive-strand RNA viruses have evolved multiple strategies to not only circumvent the hostile decay machinery but to trick it into being a priceless collaborator supporting viral RNA translation and replication. In this review, we describe the versatile interaction of positive-strand RNA viruses and [...] Read more.
Positive-strand RNA viruses have evolved multiple strategies to not only circumvent the hostile decay machinery but to trick it into being a priceless collaborator supporting viral RNA translation and replication. In this review, we describe the versatile interaction of positive-strand RNA viruses and the 5′-3′ mRNA decay machinery with a focus on the viral subversion of decapping activators. This highly conserved viral trickery is exemplified with the plant Brome mosaic virus, the animal Flock house virus and the human hepatitis C virus. Full article
(This article belongs to the Special Issue Viral Interactions with Host RNA Decay Pathways)
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1404 KiB  
Review
NMR Studies of the Structure and Function of the HIV-1 5′-Leader
by Sarah C. Keane and Michael F. Summers
Viruses 2016, 8(12), 338; https://doi.org/10.3390/v8120338 - 21 Dec 2016
Cited by 29 | Viewed by 5811
Abstract
The 5′-leader of the human immunodeficiency virus type 1 (HIV-1) genome plays several critical roles during viral replication, including differentially establishing mRNA versus genomic RNA (gRNA) fates. As observed for proteins, the function of the RNA is tightly regulated by its structure, and [...] Read more.
The 5′-leader of the human immunodeficiency virus type 1 (HIV-1) genome plays several critical roles during viral replication, including differentially establishing mRNA versus genomic RNA (gRNA) fates. As observed for proteins, the function of the RNA is tightly regulated by its structure, and a common paradigm has been that genome function is temporally modulated by structural changes in the 5′-leader. Over the past 30 years, combinations of nucleotide reactivity mapping experiments with biochemistry, mutagenesis, and phylogenetic studies have provided clues regarding the secondary structures of stretches of residues within the leader that adopt functionally discrete domains. More recently, nuclear magnetic resonance (NMR) spectroscopy approaches have been developed that enable direct detection of intra- and inter-molecular interactions within the intact leader, providing detailed insights into the structural determinants and mechanisms that regulate HIV-1 genome packaging and function. Full article
(This article belongs to the Section Animal Viruses)
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3258 KiB  
Review
Insights into Adenovirus Uncoating from Interactions with Integrins and Mediators of Host Immunity
by Glen R. Nemerow and Phoebe L. Stewart
Viruses 2016, 8(12), 337; https://doi.org/10.3390/v8120337 - 21 Dec 2016
Cited by 23 | Viewed by 5484
Abstract
Human adenoviruses are large (150 MDa) nonenveloped double-stranded DNA (dsDNA) viruses that cause acute respiratory, gastrointestinal and ocular infections. Despite these disease associations, adenovirus has aided basic and clinical research efforts through studies of its association with cells and as a target of [...] Read more.
Human adenoviruses are large (150 MDa) nonenveloped double-stranded DNA (dsDNA) viruses that cause acute respiratory, gastrointestinal and ocular infections. Despite these disease associations, adenovirus has aided basic and clinical research efforts through studies of its association with cells and as a target of host antiviral responses. This review highlights the knowledge of adenovirus disassembly and nuclear transport gleaned from structural, biophysical and functional analyses of adenovirus interactions with soluble and membrane-associated host molecules. Full article
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644 KiB  
Review
Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV)
by Joachim Denner
Viruses 2016, 8(12), 336; https://doi.org/10.3390/v8120336 - 20 Dec 2016
Cited by 20 | Viewed by 5175
Abstract
Transspecies transmission of retroviruses is a frequent event, and the human immunodeficiency virus-1 (HIV-1) is a well-known example. The gibbon ape leukaemia virus (GaLV) and koala retrovirus (KoRV), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown [...] Read more.
Transspecies transmission of retroviruses is a frequent event, and the human immunodeficiency virus-1 (HIV-1) is a well-known example. The gibbon ape leukaemia virus (GaLV) and koala retrovirus (KoRV), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. Related retroviruses have been found in Southeast Asian mice although the sequence similarity was limited. Viruses with a higher sequence homology were isolated from Melomys burtoni, the Australian and Indonesian grassland melomys. However, only the habitats of the koalas and the grassland melomys in Australia are overlapping, indicating that the melomys virus may not be the precursor of the GaLV. Viruses closely related to GaLV/KoRV were also detected in bats. Therefore, given the fact that the habitats of the gibbons in Thailand and the koalas in Australia are far away, and that bats are able to fly over long distances, the hypothesis that retroviruses of bats are the origin of GaLV and KoRV deserves consideration. Analysis of previous transspecies transmissions of retroviruses may help to evaluate the potential of transmission of related retroviruses in the future, e.g., that of porcine endogenous retroviruses (PERVs) during xenotransplantation using pig cells, tissues or organs. Full article
(This article belongs to the Section Animal Viruses)
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1431 KiB  
Review
Diverse Strategies Used by Picornaviruses to Escape Host RNA Decay Pathways
by Wendy Ullmer and Bert L. Semler
Viruses 2016, 8(12), 335; https://doi.org/10.3390/v8120335 - 20 Dec 2016
Cited by 16 | Viewed by 7072
Abstract
To successfully replicate, viruses protect their genomic material from degradation by the host cell. RNA viruses must contend with numerous destabilizing host cell processes including mRNA decay pathways and viral RNA (vRNA) degradation resulting from the antiviral response. Members of the Picornaviridae family [...] Read more.
To successfully replicate, viruses protect their genomic material from degradation by the host cell. RNA viruses must contend with numerous destabilizing host cell processes including mRNA decay pathways and viral RNA (vRNA) degradation resulting from the antiviral response. Members of the Picornaviridae family of small RNA viruses have evolved numerous diverse strategies to evade RNA decay, including incorporation of stabilizing elements into vRNA and re-purposing host stability factors. Viral proteins are deployed to disrupt and inhibit components of the decay machinery and to redirect decay machinery to the advantage of the virus. This review summarizes documented interactions of picornaviruses with cellular RNA decay pathways and processes. Full article
(This article belongs to the Special Issue Viral Interactions with Host RNA Decay Pathways)
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1959 KiB  
Article
Adenovirus with DNA Packaging Gene Mutations Increased Virus Release
by Stephen L. Wechman, Xiao-Mei Rao, Kelly M. McMasters and Heshan Sam Zhou
Viruses 2016, 8(12), 333; https://doi.org/10.3390/v8120333 - 20 Dec 2016
Cited by 17 | Viewed by 5816
Abstract
Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of [...] Read more.
Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously (Wechman, S. L. et al. Development of an Oncolytic Adenovirus with Enhanced Spread Ability through Repeated UV Irradiation and Cancer Selection. Viruses 2016, 8, 6). In this report, we show that no mutations were observed in the early genes (E1 or E4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis. Full article
(This article belongs to the Section Animal Viruses)
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1323 KiB  
Article
Israeli Acute Paralysis Virus Infection Leads to an Enhanced RNA Interference Response and Not Its Suppression in the Bumblebee Bombus terrestris
by Kaat Cappelle, Guy Smagghe, Maarten Dhaenens and Ivan Meeus
Viruses 2016, 8(12), 334; https://doi.org/10.3390/v8120334 - 19 Dec 2016
Cited by 15 | Viewed by 5006
Abstract
RNA interference (RNAi) is the primary antiviral defense system in insects and its importance for pollinator health is indisputable. In this work, we examined the effect of Israeli acute paralysis virus (IAPV) infection on the RNAi process in the bumblebee, Bombus terrestris, [...] Read more.
RNA interference (RNAi) is the primary antiviral defense system in insects and its importance for pollinator health is indisputable. In this work, we examined the effect of Israeli acute paralysis virus (IAPV) infection on the RNAi process in the bumblebee, Bombus terrestris, and whether the presence of possible functional viral suppressors could alter the potency of the host’s immune response. For this, a two-fold approach was used. Through a functional RNAi assay, we observed an enhancement of the RNAi system after IAPV infection instead of its suppression, despite only minimal upregulation of the genes involved in RNAi. Besides, the presence of the proposed suppressor 1A and the predicted OrfX protein in IAPV could not be confirmed using high definition mass spectrometry. In parallel, when bumblebees were infected with cricket paralysis virus (CrPV), known to encode a suppressor of RNAi, no increase in RNAi efficiency was seen. For both viruses, pre-infection with the one virus lead to a decreased replication of the other virus, indicating a major effect of competition. These results are compelling in the context of Dicistroviridae in multi-virus/multi-host networks as the effect of a viral infection on the RNAi machinery may influence subsequent virus infections. Full article
(This article belongs to the Section Insect Viruses)
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1333 KiB  
Article
Equine Immunoglobulin and Equine Neutralizing F(ab′)2 Protect Mice from West Nile Virus Infection
by Jiannan Cui, Yongkun Zhao, Hualei Wang, Boning Qiu, Zengguo Cao, Qian Li, Yanbo Zhang, Feihu Yan, Hongli Jin, Tiecheng Wang, Weiyang Sun, Na Feng, Yuwei Gao, Jing Sun, Yanqun Wang, Stanley Perlman, Jincun Zhao, Songtao Yang and Xianzhu Xia
Viruses 2016, 8(12), 332; https://doi.org/10.3390/v8120332 - 18 Dec 2016
Cited by 4 | Viewed by 5140
Abstract
West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to [...] Read more.
West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab′)2 fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab′)2 fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab′)2 passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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1153 KiB  
Article
Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses
by Christopher Barton, J. Calvin Kouokam, Harrell Hurst and Kenneth E. Palmer
Viruses 2016, 8(12), 331; https://doi.org/10.3390/v8120331 - 17 Dec 2016
Cited by 33 | Viewed by 7299
Abstract
Griffithsin (GRFT) is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses, including severe acute respiratory syndrome–Coronavirus (SARS-CoV), Japanese encephalitis virus (JEV), hepatitis C virus (HCV), and herpes simplex virus-2 (HSV-2). However, its pharmacokinetic profile remains largely undefined. Here, [...] Read more.
Griffithsin (GRFT) is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses, including severe acute respiratory syndrome–Coronavirus (SARS-CoV), Japanese encephalitis virus (JEV), hepatitis C virus (HCV), and herpes simplex virus-2 (HSV-2). However, its pharmacokinetic profile remains largely undefined. Here, Sprague Dawley rats were administered a single dose of GRFT at 10 or 20 mg/kg by intravenous, oral, and subcutaneous routes, respectively, and serum GRFT levels were measured at select time points. In addition, the potential for systemic accumulation after oral dosing was assessed in rats after 10 daily treatments with GRFT (20 or 40 mg/kg). We found that parenterally-administered GRFT in rats displayed a complex elimination profile, which varied according to administration routes. However, GRFT was not orally bioavailable, even after chronic treatment. Nonetheless, active GRFT capable of neutralizing HIV-Env pseudoviruses was detected in rat fecal extracts after chronic oral dosing. These findings support further evaluation of GRFT for pre-exposure prophylaxis against emerging epidemics for which specific therapeutics are not available, including systemic and enteric infections caused by susceptible enveloped viruses. In addition, GRFT should be considered for antiviral therapy and the prevention of rectal transmission of HIV-1 and other susceptible viruses. Full article
(This article belongs to the Special Issue Lectins as Antiviral)
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8364 KiB  
Article
Genetic Structure and Molecular Variability Analysis of Citrus sudden death-associated virus Isolates from Infected Plants Grown in Brazil
by Emilyn Emy Matsumura, Helvécio Della Coletta Filho, Silvia De Oliveira Dorta, Shahideh Nouri and Marcos Antonio Machado
Viruses 2016, 8(12), 330; https://doi.org/10.3390/v8120330 - 16 Dec 2016
Cited by 8 | Viewed by 4645
Abstract
Citrus sudden death-associated virus (CSDaV) is a monopartite positive-sense single-stranded RNA virus that was suggested to be associated with citrus sudden death (CSD) disease in Brazil. Here, we report the first study of the genetic structure and molecular variability among 31 CSDaV isolates [...] Read more.
Citrus sudden death-associated virus (CSDaV) is a monopartite positive-sense single-stranded RNA virus that was suggested to be associated with citrus sudden death (CSD) disease in Brazil. Here, we report the first study of the genetic structure and molecular variability among 31 CSDaV isolates collected from both symptomatic and asymptomatic trees in CSD-affected areas. Analyses of partial nucleotide sequences of five domains of the CSDaV genomic RNA, including those encoding for the methyltransferase, the multi-domain region (MDR), the helicase, the RNA-dependent RNA polymerase and the coat protein, showed that the MDR coding region was the most diverse region assessed here, and a possible association between this region and virus adaption to different host or plant tissues is considered. Overall, the nucleotide diversity (π) was low for CSDaV isolates, but the phylogenetic analyses revealed the predominance of two main groups, one of which showed a higher association with CSD-symptomatic plants. Isolates obtained from CSD-symptomatic plants, compared to those obtained from asymptomatic plants, showed higher nucleotide diversity, nonsynonymous and synonymous substitution rates and number of amino acid changes on the coding regions located closer to the 5’ end region of the genomic RNA. This work provides new insights into the genetic diversity of the CSDaV, giving support for further epidemiological studies. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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753 KiB  
Review
RNA Interference in Insect Vectors for Plant Viruses
by Surapathrudu Kanakala and Murad Ghanim
Viruses 2016, 8(12), 329; https://doi.org/10.3390/v8120329 - 12 Dec 2016
Cited by 38 | Viewed by 9144
Abstract
Insects and other arthropods are the most important vectors of plant pathogens. The majority of plant pathogens are disseminated by arthropod vectors such as aphids, beetles, leafhoppers, planthoppers, thrips and whiteflies. Transmission of plant pathogens and the challenges in managing insect vectors due [...] Read more.
Insects and other arthropods are the most important vectors of plant pathogens. The majority of plant pathogens are disseminated by arthropod vectors such as aphids, beetles, leafhoppers, planthoppers, thrips and whiteflies. Transmission of plant pathogens and the challenges in managing insect vectors due to insecticide resistance are factors that contribute to major food losses in agriculture. RNA interference (RNAi) was recently suggested as a promising strategy for controlling insect pests, including those that serve as important vectors for plant pathogens. The last decade has witnessed a dramatic increase in the functional analysis of insect genes, especially those whose silencing results in mortality or interference with pathogen transmission. The identification of such candidates poses a major challenge for increasing the role of RNAi in pest control. Another challenge is to understand the RNAi machinery in insect cells and whether components that were identified in other organisms are also present in insect. This review will focus on summarizing success cases in which RNAi was used for silencing genes in insect vector for plant pathogens, and will be particularly helpful for vector biologists. Full article
(This article belongs to the Special Issue Molecular Plant Virus—Insect Vector Interactions)
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2255 KiB  
Article
Serro 2 Virus Highlights the Fundamental Genomic and Biological Features of a Natural Vaccinia Virus Infecting Humans
by Giliane De Souza Trindade, Ginny L. Emerson, Scott Sammons, Michael Frace, Dhwani Govil, Bruno Eduardo Fernandes Mota, Jônatas Santos Abrahão, Felipe Lopes De Assis, Melissa Olsen-Rasmussen, Cynthia S. Goldsmith, Yu Li, Darin Carroll, Flavio Guimarães da Fonseca, Erna Kroon and Inger K. Damon
Viruses 2016, 8(12), 328; https://doi.org/10.3390/v8120328 - 10 Dec 2016
Cited by 16 | Viewed by 5793
Abstract
Vaccinia virus (VACV) has been implicated in infections of dairy cattle and humans, and outbreaks have substantially impacted local economies and public health in Brazil. During a 2005 outbreak, a VACV strain designated Serro 2 virus (S2V) was collected from a 30-year old [...] Read more.
Vaccinia virus (VACV) has been implicated in infections of dairy cattle and humans, and outbreaks have substantially impacted local economies and public health in Brazil. During a 2005 outbreak, a VACV strain designated Serro 2 virus (S2V) was collected from a 30-year old male milker. Our aim was to phenotypically and genetically characterize this VACV Brazilian isolate. S2V produced small round plaques without associated comets when grown in BSC40 cells. Furthermore, S2V was less virulent than the prototype strain VACV-Western Reserve (WR) in a murine model of intradermal infection, producing a tiny lesion with virtually no surrounding inflammation. The genome of S2V was sequenced by primer walking. The coding region spans 184,572 bp and contains 211 predicted genes. Mutations in envelope genes specifically associated with small plaque phenotypes were not found in S2V; however, other alterations in amino acid sequences within these genes were identified. In addition, some immunomodulatory genes were truncated in S2V. Phylogenetic analysis using immune regulatory-related genes, besides the hemagglutinin gene, segregated the Brazilian viruses into two clusters, grouping the S2V into Brazilian VACV group 1. S2V is the first naturally-circulating human-associated VACV, with a low passage history, to be extensively genetically and phenotypically characterized. Full article
(This article belongs to the Section Animal Viruses)
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38236 KiB  
Article
Characterization of an Immunodominant Epitope in the Endodomain of the Coronavirus Membrane Protein
by Hui Dong, Xin Zhang, Hongyan Shi, Jianfei Chen, Da Shi, Yunnuan Zhu and Li Feng
Viruses 2016, 8(12), 327; https://doi.org/10.3390/v8120327 - 10 Dec 2016
Cited by 3 | Viewed by 5314
Abstract
The coronavirus membrane (M) protein acts as a dominant immunogen and is a major player in virus assembly. In this study, we prepared two monoclonal antibodies (mAbs; 1C3 and 4C7) directed against the transmissible gastroenteritis virus (TGEV) M protein. The 1C3 and 4C7 [...] Read more.
The coronavirus membrane (M) protein acts as a dominant immunogen and is a major player in virus assembly. In this study, we prepared two monoclonal antibodies (mAbs; 1C3 and 4C7) directed against the transmissible gastroenteritis virus (TGEV) M protein. The 1C3 and 4C7 mAbs both reacted with the native TGEV M protein in western blotting and immunofluorescence (IFA) assays. Two linear epitopes, 243YSTEART249 (1C3) and 243YSTEARTDNLSEQEKLLHMV262 (4C7), were identified in the endodomain of the TGEV M protein. The 1C3 mAb can be used for the detection of the TGEV M protein in different assays. An IFA method for the detection of TGEV M protein was optimized using mAb 1C3. Furthermore, the ability of the epitope identified in this study to stimulate antibody production was also evaluated. An immunodominant epitope in the TGEV membrane protein endodomain was identified. The results of this study have implications for further research on TGEV replication. Full article
(This article belongs to the Special Issue Porcine Viruses)
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1440 KiB  
Article
Evaluation of microRNA Expression in Patients with Herpes Zoster
by Xihan Li, Ying Huang, Yucheng Zhang and Na He
Viruses 2016, 8(12), 326; https://doi.org/10.3390/v8120326 - 02 Dec 2016
Cited by 11 | Viewed by 4620
Abstract
Reactivated varicella-zoster virus (VZV), which lies latent in the dorsal root ganglions and cranial nerves before its reactivation, is capable of causing herpes zoster (HZ), but the specific mechanism of virus reactivation and latency remains unknown. It was proposed that circulating microRNAs (miRNAs) [...] Read more.
Reactivated varicella-zoster virus (VZV), which lies latent in the dorsal root ganglions and cranial nerves before its reactivation, is capable of causing herpes zoster (HZ), but the specific mechanism of virus reactivation and latency remains unknown. It was proposed that circulating microRNAs (miRNAs) in body fluids could potentially indicate infection. However, the connection between herpes zoster and circulating miRNAs has not been demonstrated. In this study, 41 HZ patients without superinfection were selected. The serum miRNA levels were analyzed by TaqMan low density array (TLDA) and confirmed individually by quantitative reverse transcription PCR (RT-qPCR) analysis. Thirty-five age-matched subjects without any infectious diseases or inflammation were selected as controls. The results showed that the serum miRNA expression profiles in 41 HZ patients were different from those of control subjects. Specifically, 18 miRNAs were up-regulated and 126 were down-regulated more than two-fold in HZ patients compared with controls. The subsequent confirmation of these results by qRT-PCR, as well as receiver operating characteristic (ROC) curve analysis, revealed that six kinds of miRNAs, including miR-190b, miR-571, miR-1276, miR-1303, miR-943, and miR-661, exhibited statistically significant enhanced expression levels (more than four-fold) in HZ patients, compared with those of healthy controls and herpes simplex virus (HSV) patients. Subsequently, it is proposed that these circulating miRNAs are capable of regulating numerous pathways and some may even participate in the inflammatory response or nervous system activity. This study has initially demonstrated that the serum miRNA expression profiles in HZ patients were different from those of uninfected individuals. Additionally, these findings also suggest that six of the altered miRNA could be potentially used as biomarkers to test for latent HZ infection. Full article
(This article belongs to the Section Animal Viruses)
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1677 KiB  
Article
Ion Channel Activity of Vpu Proteins Is Conserved throughout Evolution of HIV-1 and SIV
by Timo Greiner, Sebastian Bolduan, Brigitte Hertel, Christine Groß, Kay Hamacher, Ulrich Schubert, Anna Moroni and Gerhard Thiel
Viruses 2016, 8(12), 325; https://doi.org/10.3390/v8120325 - 01 Dec 2016
Cited by 6 | Viewed by 6022
Abstract
The human immunodeficiency virus type 1 (HIV-1) protein Vpu is encoded exclusively by HIV-1 and related simian immunodeficiency viruses (SIVs). The transmembrane domain of the protein has dual functions: it counteracts the human restriction factor tetherin and forms a cation channel. Since these [...] Read more.
The human immunodeficiency virus type 1 (HIV-1) protein Vpu is encoded exclusively by HIV-1 and related simian immunodeficiency viruses (SIVs). The transmembrane domain of the protein has dual functions: it counteracts the human restriction factor tetherin and forms a cation channel. Since these two functions are causally unrelated it remains unclear whether the channel activity has any relevance for viral release and replication. Here we examine structure and function correlates of different Vpu homologs from HIV-1 and SIV to understand if ion channel activity is an evolutionary conserved property of Vpu proteins. An electrophysiological testing of Vpus from different HIV-1 groups (N and P) and SIVs from chimpanzees (SIVcpz), and greater spot-nosed monkeys (SIVgsn) showed that they all generate channel activity in HEK293T cells. This implies a robust and evolutionary conserved channel activity and suggests that cation conductance may also have a conserved functional significance. Full article
(This article belongs to the Section Animal Viruses)
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4352 KiB  
Article
Capsule-Targeting Depolymerase, Derived from Klebsiella KP36 Phage, as a Tool for the Development of Anti-Virulent Strategy
by Grażyna Majkowska-Skrobek, Agnieszka Łątka, Rita Berisio, Barbara Maciejewska, Flavia Squeglia, Maria Romano, Rob Lavigne, Carsten Struve and Zuzanna Drulis-Kawa
Viruses 2016, 8(12), 324; https://doi.org/10.3390/v8120324 - 01 Dec 2016
Cited by 88 | Viewed by 8637
Abstract
The rise of antibiotic-resistant Klebsiella pneumoniae, a leading nosocomial pathogen, prompts the need for alternative therapies. We have identified and characterized a novel depolymerase enzyme encoded by Klebsiella phage KP36 (depoKP36), from the Siphoviridae family. To gain insights into the catalytic and [...] Read more.
The rise of antibiotic-resistant Klebsiella pneumoniae, a leading nosocomial pathogen, prompts the need for alternative therapies. We have identified and characterized a novel depolymerase enzyme encoded by Klebsiella phage KP36 (depoKP36), from the Siphoviridae family. To gain insights into the catalytic and structural features of depoKP36, we have recombinantly produced this protein of 93.4 kDa and showed that it is able to hydrolyze a crude exopolysaccharide of a K. pneumoniae host. Using in vitro and in vivo assays, we found that depoKP36 was also effective against a native capsule of clinical K. pneumoniae strains, representing the K63 type, and significantly inhibited Klebsiella-induced mortality of Galleria mellonella larvae in a time-dependent manner. DepoKP36 did not affect the antibiotic susceptibility of Klebsiella strains. The activity of this enzyme was retained in a broad range of pH values (4.0–7.0) and temperatures (up to 45 °C). Consistently, the circular dichroism (CD) spectroscopy revealed a highly stability with melting transition temperature (Tm) = 65 °C. In contrast to other phage tailspike proteins, this enzyme was susceptible to sodium dodecyl sulfate (SDS) denaturation and proteolytic cleavage. The structural studies in solution showed a trimeric arrangement with a high β-sheet content. Our findings identify depoKP36 as a suitable candidate for the development of new treatments for K. pneumoniae infections. Full article
(This article belongs to the Special Issue Viruses of Microbes)
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Article
Comparative Proteome Analysis of Porcine Jejunum Tissues in Response to a Virulent Strain of Porcine Epidemic Diarrhea Virus and Its Attenuated Strain
by Zhonghua Li, Fangzhou Chen, Shiyi Ye, Xiaozhen Guo, Atta Muhanmmad Memon, Meizhou Wu and Qigai He
Viruses 2016, 8(12), 323; https://doi.org/10.3390/v8120323 - 29 Nov 2016
Cited by 32 | Viewed by 5746
Abstract
Porcine epidemic diarrhea virus (PEDV), a predominant cause of acute enteric infection, leads to severe dehydrating diarrhea and mortality in piglets all over the world. A virulent PEDV YN13 strain, isolated in our laboratory, was attenuated to yield an attenuated PEDV strain YN144. [...] Read more.
Porcine epidemic diarrhea virus (PEDV), a predominant cause of acute enteric infection, leads to severe dehydrating diarrhea and mortality in piglets all over the world. A virulent PEDV YN13 strain, isolated in our laboratory, was attenuated to yield an attenuated PEDV strain YN144. To better understand the pathogenesis mechanism and the virus-host interaction during infection with both PEDV YN13 and YN144 strains, a comparative proteomic analysis was carried out to investigate the proteomic changes produced in the primary target organ, using isobaric tags for relative and absolute quantitation (iTRAQ) labeling, followed by liquid chromatography tandem-mass spectrometry (LC-MS/MS). A total of 269 and 301 differently expressed proteins (DEPs) were identified in the jejunum tissues of the piglets inoculated with YN13 and YN144, respectively. Bioinformatics analysis revealed that these proteins were involved in stress responses, signal transduction, and the immune system. All of these involved interferon-stimulated genes (ISGs) which were up-regulated in jejunums by both of the PEDV-infected groups. Based on the comparative analysis, we proposed that different changes induced by YN13 and YN144 in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), eukaryotic initiation factor 4G1 (eIF4G1), and some members in the heat shock protein (HSP) family, may be responsible for differences in their pathogenicity. Full article
(This article belongs to the Section Animal Viruses)
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Article
Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models
by Rodrigo Delvecchio, Luiza M. Higa, Paula Pezzuto, Ana Luiza Valadão, Patrícia P. Garcez, Fábio L. Monteiro, Erick C. Loiola, André A. Dias, Fábio J. M. Silva, Matthew T. Aliota, Elizabeth A. Caine, Jorge E. Osorio, Maria Bellio, David H. O’Connor, Stevens Rehen, Renato Santana De Aguiar, Andrea Savarino, Loraine Campanati and Amilcar Tanuri
Viruses 2016, 8(12), 322; https://doi.org/10.3390/v8120322 - 29 Nov 2016
Cited by 221 | Viewed by 17801
Abstract
Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is [...] Read more.
Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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Article
Analyses of Evolutionary Characteristics of the Hemagglutinin-Esterase Gene of Influenza C Virus during a Period of 68 Years Reveals Evolutionary Patterns Different from Influenza A and B Viruses
by Yuki Furuse, Yoko Matsuzaki, Hidekazu Nishimura and Hitoshi Oshitani
Viruses 2016, 8(12), 321; https://doi.org/10.3390/v8120321 - 26 Nov 2016
Cited by 17 | Viewed by 5897
Abstract
Infections with the influenza C virus causing respiratory symptoms are common, particularly among children. Since isolation and detection of the virus are rarely performed, compared with influenza A and B viruses, the small number of available sequences of the virus makes it difficult [...] Read more.
Infections with the influenza C virus causing respiratory symptoms are common, particularly among children. Since isolation and detection of the virus are rarely performed, compared with influenza A and B viruses, the small number of available sequences of the virus makes it difficult to analyze its evolutionary dynamics. Recently, we reported the full genome sequence of 102 strains of the virus. Here, we exploited the data to elucidate the evolutionary characteristics and phylodynamics of the virus compared with influenza A and B viruses. Along with our data, we obtained public sequence data of the hemagglutinin-esterase gene of the virus; the dataset consists of 218 unique sequences of the virus collected from 14 countries between 1947 and 2014. Informatics analyses revealed that (1) multiple lineages have been circulating globally; (2) there have been weak and infrequent selective bottlenecks; (3) the evolutionary rate is low because of weak positive selection and a low capability to induce mutations; and (4) there is no significant positive selection although a few mutations affecting its antigenicity have been induced. The unique evolutionary dynamics of the influenza C virus must be shaped by multiple factors, including virological, immunological, and epidemiological characteristics. Full article
(This article belongs to the Section Animal Viruses)
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