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Viruses, Volume 11, Issue 10 (October 2019)

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Open AccessReview
The Symmetry of Viral Sialic Acid Binding Sites–Implications for Antiviral Strategies
Viruses 2019, 11(10), 947; https://doi.org/10.3390/v11100947 (registering DOI) - 14 Oct 2019
Abstract
Virus infections are initiated by the attachment of the viral particle to protein or carbohydrate receptors on the host cell. Sialic acid-bearing glycan structures are prominently displayed at the cell surface, and, consequently, these structures can function as receptors for a large number [...] Read more.
Virus infections are initiated by the attachment of the viral particle to protein or carbohydrate receptors on the host cell. Sialic acid-bearing glycan structures are prominently displayed at the cell surface, and, consequently, these structures can function as receptors for a large number of diverse viruses. Structural biology research has helped to establish the molecular bases for many virus–sialic acid interactions. Due to the icosahedral 532 point group symmetry that underlies many viral capsids, the receptor binding sites are frequently arranged in a highly symmetric fashion and linked by five-fold, three-fold, or two-fold rotation axes. For the inhibition of viral attachment, one emerging strategy is based on developing multivalent sialic acid-based inhibitors that can simultaneously engage several of these binding sites, thus binding viral capsids with high avidity. In this review, we will evaluate the structures of non-enveloped virus capsid proteins bound to sialylated glycan receptors and discuss the potential of these structures for the development of potent antiviral attachment inhibitors. Full article
(This article belongs to the Special Issue Viral Entry Pathways)
Open AccessCommunication
The First Detection of Equine Coronavirus in Adult Horses and Foals in Ireland
Viruses 2019, 11(10), 946; https://doi.org/10.3390/v11100946 (registering DOI) - 14 Oct 2019
Abstract
The objective of this study was to investigate the presence of equine coronavirus (ECoV) in clinical samples submitted to a diagnostic laboratory in Ireland. A total of 424 clinical samples were examined from equids with enteric disease in 24 Irish counties between 2011 [...] Read more.
The objective of this study was to investigate the presence of equine coronavirus (ECoV) in clinical samples submitted to a diagnostic laboratory in Ireland. A total of 424 clinical samples were examined from equids with enteric disease in 24 Irish counties between 2011 and 2015. A real-time reverse transcription polymerase chain reaction was used to detect ECoV RNA. Nucleocapsid, spike and the region from the p4.7 to p12.7 genes of positive samples were sequenced, and sequence and phylogenetic analyses were conducted. Five samples (1.2%) collected in 2011 and 2013 tested positive for ECoV. Positive samples were collected from adult horses, Thoroughbred foals and a donkey foal. Sequence and/or phylogenetic analysis showed that nucleocapsid, spike and p12.7 genes were highly conserved and were closely related to ECoVs identified in other countries. In contrast, the region from p4.7 and the non-coding region following the p4.7 gene had deletions or insertions. The differences in the p4.7 region between the Irish ECoVs and other ECoVs indicated that the Irish viruses were distinguishable from those circulating in other countries. This is the first report of ECoV detected in both foals and adult horses in Ireland. Full article
(This article belongs to the Special Issue Equine Viruses)
Open AccessReview
Pre-Transplantation Assessment of BK Virus Serostatus: Significance, Current Methods, and Obstacles
Viruses 2019, 11(10), 945; https://doi.org/10.3390/v11100945 (registering DOI) - 14 Oct 2019
Abstract
The immunosuppression required for graft tolerance in kidney transplant patients can trigger latent BK polyomavirus (BKPyV) reactivation, and the infection can progress to nephropathy and graft rejection. It has been suggested that pre-transplantation BKPyV serostatus in donors and recipients is a predictive marker [...] Read more.
The immunosuppression required for graft tolerance in kidney transplant patients can trigger latent BK polyomavirus (BKPyV) reactivation, and the infection can progress to nephropathy and graft rejection. It has been suggested that pre-transplantation BKPyV serostatus in donors and recipients is a predictive marker for post-transplantation BKPyV replication. The fact that research laboratories have used many different assay techniques to determine BKPyV serostatus complicates these data analysis. Even studies based on the same technique differed in their standard controls choice, the antigenic structure type used for detection, and the cut-off for seropositivity. Here, we review the different BKPyV VP1 antigens types used for detection and consider the various BKPyV serostatus assay techniques’ advantages and disadvantages. Lastly, we highlight the obstacles in the implementation of a consensual BKPyV serologic assay in clinics (e.g., the guidelines absence in this field). Full article
(This article belongs to the Section Animal Viruses)
Open AccessReview
Canine and Phocine Distemper Viruses: Global Spread and Genetic Basis of Jumping Species Barriers
Viruses 2019, 11(10), 944; https://doi.org/10.3390/v11100944 (registering DOI) - 14 Oct 2019
Abstract
Canine distemper virus (CDV) and phocine distemper (PDV) are closely-related members of the Paramyxoviridae family, genus morbillivirus, in the order Mononegavirales. CDV has a broad host range among carnivores. PDV is thought to be derived from CDV through contact between terrestrial [...] Read more.
Canine distemper virus (CDV) and phocine distemper (PDV) are closely-related members of the Paramyxoviridae family, genus morbillivirus, in the order Mononegavirales. CDV has a broad host range among carnivores. PDV is thought to be derived from CDV through contact between terrestrial carnivores and seals. PDV has caused extensive mortality in Atlantic seals and other marine mammals, and more recently has spread to the North Pacific Ocean. CDV also infects marine carnivores, and there is evidence of morbillivirus infection of seals and other species in Antarctica. Recently, CDV has spread to felines and other wildlife species in the Serengeti and South Africa. Some CDV vaccines may also have caused wildlife disease. Changes in the virus haemagglutinin (H) protein, particularly the signaling lymphocyte activation molecule (SLAM) receptor binding site, correlate with adaptation to non-canine hosts. Differences in the phosphoprotein (P) gene sequences between disease and non-disease causing CDV strains may relate to pathogenicity in domestic dogs and wildlife. Of most concern are reports of CDV infection and disease in non-human primates raising the possibility of zoonosis. In this article we review the global occurrence of CDV and PDV, and present both historical and genetic information relating to these viruses crossing species barriers. Full article
(This article belongs to the Special Issue Morbilliviruses)
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Open AccessArticle
dsRNA-Seq: Identification of Viral Infection by Purifying and Sequencing dsRNA
Viruses 2019, 11(10), 943; https://doi.org/10.3390/v11100943 (registering DOI) - 14 Oct 2019
Abstract
RNA viruses are a major source of emerging and re-emerging infectious diseases around the world. We developed a method to identify RNA viruses that is based on the fact that RNA viruses produce double-stranded RNA (dsRNA) while replicating. Purifying and sequencing dsRNA from [...] Read more.
RNA viruses are a major source of emerging and re-emerging infectious diseases around the world. We developed a method to identify RNA viruses that is based on the fact that RNA viruses produce double-stranded RNA (dsRNA) while replicating. Purifying and sequencing dsRNA from the total RNA isolated from infected tissue allowed us to recover dsRNA virus sequences and replicated sequences from single-stranded RNA (ssRNA) viruses. We refer to this approach as dsRNA-Seq. By assembling dsRNA sequences into contigs we identified full length or partial RNA viral genomes of varying genome types infecting mammalian culture samples, identified a known viral disease agent in laboratory infected mice, and successfully detected naturally occurring RNA viral infections in reptiles. Here, we show that dsRNA-Seq is a preferable method for identifying viruses in organisms that don’t have sequenced genomes and/or commercially available rRNA depletion reagents. In addition, a significant advantage of this method is the ability to identify replicated viral sequences of ssRNA viruses, which is useful for distinguishing infectious viral agents from potential noninfectious viral particles or contaminants. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Viruses in Horses with Neurologic and Respiratory Diseases
Viruses 2019, 11(10), 942; https://doi.org/10.3390/v11100942 (registering DOI) - 14 Oct 2019
Abstract
Metagenomics was used to identify viral sequences in the plasma and CSF (cerobrospinal fluid) of 13 horses with unexplained neurological signs and in the plasma and respiratory swabs of 14 horses with unexplained respiratory signs. Equine hepacivirus and two copiparvoviruses (horse parvovirus-CSF and [...] Read more.
Metagenomics was used to identify viral sequences in the plasma and CSF (cerobrospinal fluid) of 13 horses with unexplained neurological signs and in the plasma and respiratory swabs of 14 horses with unexplained respiratory signs. Equine hepacivirus and two copiparvoviruses (horse parvovirus-CSF and a novel parvovirus) were detected in plasma from neurological cases. Plasma from horses with respiratory signs contained the same two copiparvoviruses plus equine pegivirus D and respiratory swabs contained equine herpes virus 2 and 5. Based on genetic distances the novel copiparvovirus qualified as a member of a new parvovirus species we named Eqcopivirus. These samples plus another 41 plasma samples from healthy horses were tested by real-time PCRs for multiple equine parvoviruses and hepacivirus. Over half the samples tested were positive for one to three viruses with eqcopivirus DNA detected in 20.5%, equine hepacivirus RNA and equine parvovirus-H DNA in 16% each, and horse parvovirus-CSF DNA in 12% of horses. Comparing viral prevalence in plasma none of the now three genetically characterized equine parvoviruses (all in the copiparvovirus genus) was significantly associated with neurological and respiratory signs in this limited sampling. Full article
(This article belongs to the Special Issue Equine Viruses)
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Open AccessArticle
Vector Competence of Italian Populations of Culicoides for Some Bluetongue Virus Strains Responsible for Recent Northern African and European Outbreaks
Viruses 2019, 11(10), 941; https://doi.org/10.3390/v11100941 - 12 Oct 2019
Viewed by 129
Abstract
The distribution of Bluetongue virus (BTV) in Europe can be represented by two distinct and interconnected epidemiological systems (episystems), each characterized by different ecological characteristics and vector species. This study investigated the vector competence of Italian populations of Culicoides imicola and Culicoides obsoletus/scoticus [...] Read more.
The distribution of Bluetongue virus (BTV) in Europe can be represented by two distinct and interconnected epidemiological systems (episystems), each characterized by different ecological characteristics and vector species. This study investigated the vector competence of Italian populations of Culicoides imicola and Culicoides obsoletus/scoticus to some representative BTV strains after artificial oral infection. The BTV strains were selected according to their ability to spread to one or both episystems and included BTV-4 ITA, responsible of the recent Italian and French BTV-4 outbreaks; the BTV-2 strain which caused the first BTV incursion in Italy, Corsica, and Balearic Islands; BTV-4 MOR, responsible for the epidemic in Morocco; and BTV-8, the strain which spread through Europe between 2006 and 2008. Blood-soaked cotton pledgets and Hemotek membrane feeder using Parafilm® membrane were used to artificially feed midges. For each population/strain, recovery rates (positive/tested heads) were evaluated using serogroup- and serotype-specific RT-PCR. The trial demonstrated that, except for the Abruzzo population of C. obsoletus/C. scoticus, which was refractory to BTV-4 MOR infection, all the investigated Culicoides populations are susceptible to the selected BTV strains and that, if prompt vaccination programs and restriction measures had not been implemented, BTV-2 and BTV-4 MOR could have spread all over Europe. Full article
(This article belongs to the Special Issue Virus-Vector-Host Interactions of Culicoides-Borne Diseases)
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Open AccessReview
Nosocomial Transmission of Emerging Viruses via Aerosol-Generating Medical Procedures
Viruses 2019, 11(10), 940; https://doi.org/10.3390/v11100940 - 12 Oct 2019
Viewed by 163
Abstract
Recent nosocomial transmission events of emerging and re-emerging viruses, including Ebola virus, Middle East respiratory syndrome coronavirus, Nipah virus, and Crimean–Congo hemorrhagic fever orthonairovirus, have highlighted the risk of nosocomial transmission of emerging viruses in health-care settings. In particular, concerns and precautions have [...] Read more.
Recent nosocomial transmission events of emerging and re-emerging viruses, including Ebola virus, Middle East respiratory syndrome coronavirus, Nipah virus, and Crimean–Congo hemorrhagic fever orthonairovirus, have highlighted the risk of nosocomial transmission of emerging viruses in health-care settings. In particular, concerns and precautions have increased regarding the use of aerosol-generating medical procedures when treating patients with such viral infections. In spite of increasing associations between aerosol-generating medical procedures and the nosocomial transmission of viruses, we still have a poor understanding of the risks of specific procedures and viruses. In order to identify which aerosol-generating medical procedures and emerging viruses pose a high risk to health-care workers, we explore the mechanisms of aerosol-generating medical procedures, as well as the transmission pathways and characteristics of highly pathogenic viruses associated with nosocomial transmission. We then propose how research, both in clinical and experimental settings, could advance current infection control guidelines. Full article
(This article belongs to the Special Issue Emerging Viruses: Surveillance, Prevention, Evolution and Control)
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Open AccessConference Report
The XIth International Symposium on Thysanoptera and Tospoviruses Co-sponsored by Yunnan Academy of Agricultural Sciences and Nanjing Agricultural University in Kunming, China 2019
Viruses 2019, 11(10), 939; https://doi.org/10.3390/v11100939 - 12 Oct 2019
Viewed by 132
Abstract
The XIth International Symposium on Thysanoptera and Tospoviruses co-hosted by the Yunnan Academy of Agricultural Sciences, and Nanjing Agricultural University was held from September 21–25 in Kunming, China (Figure 1) [...] Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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Open AccessArticle
High Fidelity Deep Sequencing Reveals No Effect of ATM, ATR, and DNA-PK Cellular DNA Damage Response Pathways on Adenovirus Mutation Rate
Viruses 2019, 11(10), 938; https://doi.org/10.3390/v11100938 - 11 Oct 2019
Viewed by 160
Abstract
Most DNA viruses exhibit relatively low rates of spontaneous mutation. However, the molecular mechanisms underlying DNA virus genetic stability remain unclear. In principle, mutation rates should not depend solely on polymerase fidelity, but also on factors such as DNA damage and repair efficiency. [...] Read more.
Most DNA viruses exhibit relatively low rates of spontaneous mutation. However, the molecular mechanisms underlying DNA virus genetic stability remain unclear. In principle, mutation rates should not depend solely on polymerase fidelity, but also on factors such as DNA damage and repair efficiency. Most eukaryotic DNA viruses interact with the cellular DNA damage response (DDR), but the role of DDR pathways in preventing mutations in the virus has not been tested empirically. To address this goal, we serially transferred human adenovirus type 5 in cells in which the telangiectasia-mutated PI3K-related protein kinase (ATM), the ATM/Rad3-related (ATR) kinase, and the DNA-dependent protein kinase (DNA-PK) were chemically inactivated, as well as in control cells displaying normal DDR pathway functioning. High-fidelity deep sequencing of these viral populations revealed mutation frequencies in the order of one-millionth, with no detectable effect of the inactivation of DDR mediators ATM, ATR, and DNA-PK on adenovirus sequence variability. This suggests that these DDR pathways do not play a major role in determining adenovirus genetic diversity. Full article
(This article belongs to the Section Animal Viruses)
Open AccessArticle
Methyl-Beta-Cyclodextrin-Induced Macropinocytosis Results in Increased Infection of Sf21 Cells by Bombyx Mori Nucleopolyhedrovirus
Viruses 2019, 11(10), 937; https://doi.org/10.3390/v11100937 - 11 Oct 2019
Viewed by 154
Abstract
Bombyx mori nucleopolyhedrovirus (BmNPV) is closely related to Autographa californica multiple nucleopolyhedrovirus (AcMNPV) with over ~93% amino acid sequence identity. However, their host ranges are essentially nonoverlapping. The mechanism of BmNPV entry into host cells is completely different from that of AcMNPV, and [...] Read more.
Bombyx mori nucleopolyhedrovirus (BmNPV) is closely related to Autographa californica multiple nucleopolyhedrovirus (AcMNPV) with over ~93% amino acid sequence identity. However, their host ranges are essentially nonoverlapping. The mechanism of BmNPV entry into host cells is completely different from that of AcMNPV, and whether the entry mechanism difference relates to the host range remains unclear. BmNPV produces an abortive infection in nonhost cells due to virion nuclear transportation failure. Here, we performed a detailed study by increasing BmNPV infection in Sf21 cells with the aid of methyl-beta-cyclodextrin (MβCD). We found that low-concentration MβCD incubation efficiently activates membrane ruffling in Sf21 cells, which mediates the increase in BmNPV infection. Interestingly, MβCD incubation after virion internalization also increases the infection, which suggests that macropinocytosis is involved in BmNPV infection in Sf21 cells after virion internalization. Further study revealed that clathrin-mediated endocytosis (CME) is employed by BmNPV to facilitate entry into Sf21 cells, and chlorpromazine application abolishes BmNPV infection in cells incubated both with and without MβCD. Based on these studies, we show that BmNPV enters Sf21 cells via CME and that parallel induction of macropinocytosis facilitates BmNPV infection in Sf21 cells. This study reveals the mechanism of BmNPV entry into Sf21 cells and provides clues for improving BmNPV infections in nonpermissive cells. Full article
(This article belongs to the Section Insect Viruses)
Open AccessArticle
Cross-Protection of Inactivated Rabies Vaccines for Veterinary Use against Bat Lyssaviruses Occurring in Europe
Viruses 2019, 11(10), 936; https://doi.org/10.3390/v11100936 - 11 Oct 2019
Viewed by 137
Abstract
Human rabies vaccines have been shown to induce partial protection against members of phylogroup I bat lyssaviruses. Here, we investigated the capacity of a widely used rabies inactivated vaccine (Rabisin, Boehringer-Ingelheim) for veterinary use to cross-protect mice experimentally infected with European bat lyssavirus [...] Read more.
Human rabies vaccines have been shown to induce partial protection against members of phylogroup I bat lyssaviruses. Here, we investigated the capacity of a widely used rabies inactivated vaccine (Rabisin, Boehringer-Ingelheim) for veterinary use to cross-protect mice experimentally infected with European bat lyssavirus 1 (EBLV-1b), European bat lyssavirus 2 (EBLV-2), and Bokeloh bat lyssavirus (BBLV) occurring in Europe. For each lyssavirus, we investigated the efficacy of two different doses of vaccine against two viral doses administrated by either central or peripheral routes. In parallel, seroconversion following pre-exposure vaccination was investigated. In this study, we demonstrated that the three investigated bat isolates were pathogenic, even at low dose, when inoculated by the central route but were not/less pathogenic when administrated peripherally. The Rabisin vaccine was capable of significantly cross-protecting mice inoculated intramuscularly with EBLV-1b and EBLV-2 and intracerebrally with BBLV. The level of rabies neutralizing antibodies induced by the Rabisin was quite high against the bat lyssaviruses, but with no significant differences between immunization with 1 and 5 IU/dose. The study emphasizes that the quality of rabies-inactivated vaccines for veterinary use is of utmost importance to optimize the cross-protection of pets against phylogroup I bat lyssaviruses occurring in Europe. Full article
(This article belongs to the Special Issue Rabies Virus: Knowledge Gaps and Challenges to Elimination)
Open AccessArticle
Quantitative Microscopy Reveals Stepwise Alteration of Chromatin Structure during Herpesvirus Infection
Viruses 2019, 11(10), 935; https://doi.org/10.3390/v11100935 - 11 Oct 2019
Viewed by 176
Abstract
During lytic herpes simplex virus 1 (HSV-1) infection, the expansion of the viral replication compartments leads to an enrichment of the host chromatin in the peripheral nucleoplasm. We have shown previously that HSV-1 infection induces the formation of channels through the compacted peripheral [...] Read more.
During lytic herpes simplex virus 1 (HSV-1) infection, the expansion of the viral replication compartments leads to an enrichment of the host chromatin in the peripheral nucleoplasm. We have shown previously that HSV-1 infection induces the formation of channels through the compacted peripheral chromatin. Here, we used three-dimensional confocal and expansion microscopy, soft X-ray tomography, electron microscopy, and random walk simulations to analyze the kinetics of host chromatin redistribution and capsid localization relative to their egress site at the nuclear envelope. Our data demonstrated a gradual increase in chromatin marginalization, and the kinetics of chromatin smoothening around the viral replication compartments correlated with their expansion. We also observed a gradual transfer of capsids to the nuclear envelope. Later in the infection, random walk modeling indicated a gradually faster transport of capsids to the nuclear envelope that correlated with an increase in the interchromatin channels in the nuclear periphery. Our study reveals a stepwise and time-dependent mechanism of herpesvirus nuclear egress, in which progeny viral capsids approach the egress sites at the nuclear envelope via interchromatin spaces. Full article
(This article belongs to the Section Animal Viruses)
Open AccessArticle
Structural Pattern Differences in Unbranched Rod-like RNA of Hepatitis Delta Virus affect RNA Editing
Viruses 2019, 11(10), 934; https://doi.org/10.3390/v11100934 - 11 Oct 2019
Viewed by 169
Abstract
Hepatitis delta virus (HDV) RNA forms an unbranched rod-like structure and complexes with the delta antigen (HDAg). Host ADAR1-catalyzed RNA editing at the amber/W site of the small HDAg leads to the production of the large HDAg, which inhibits replication and is required [...] Read more.
Hepatitis delta virus (HDV) RNA forms an unbranched rod-like structure and complexes with the delta antigen (HDAg). Host ADAR1-catalyzed RNA editing at the amber/W site of the small HDAg leads to the production of the large HDAg, which inhibits replication and is required for virion assembly. For HDV genotype 1, amber/W editing is controlled by HDAg and the RNA structure immediate vicinity and downstream of the editing site. Here, the effects of 20 mutants carrying an increased length of consecutive base-pairing at various sites in HDV RNA on amber/W site editing were examined. All nine mutants carrying genomic regions that formed up to 15 consecutive base pairs, which is also the maximum length observed in 41 naturally occurring HDV genomes, showed normal editing rate. However, mutants carrying a 16 or 17 consecutive base-paired antigenomic segment located as far as 114 nt upstream could increase editing efficiency, possibly by interfering with HDAg binding. These data show for the first time that extended base-pairing upstream of the amber/W site could increase HDV RNA editing efficiency. Furthermore, it appears that the naturally occurring HDV RNA structures have been selected for suboptimal amber/W RNA editing, which favors the HDV replication cycle. Full article
(This article belongs to the Section Animal Viruses)
Open AccessArticle
A Bivalent Live-Attenuated Vaccine for the Prevention of Equine Influenza Virus
Viruses 2019, 11(10), 933; https://doi.org/10.3390/v11100933 - 11 Oct 2019
Viewed by 111
Abstract
Vaccination remains the most effective approach for preventing and controlling equine influenza virus (EIV) in horses. However, the ongoing evolution of EIV has increased the genetic and antigenic differences between currently available vaccines and circulating strains, resulting in suboptimal vaccine efficacy. As recommended [...] Read more.
Vaccination remains the most effective approach for preventing and controlling equine influenza virus (EIV) in horses. However, the ongoing evolution of EIV has increased the genetic and antigenic differences between currently available vaccines and circulating strains, resulting in suboptimal vaccine efficacy. As recommended by the World Organization for Animal Health (OIE), the inclusion of representative strains from clade 1 and clade 2 Florida sublineages of EIV in vaccines may maximize the protection against presently circulating viral strains. In this study, we used reverse genetics technologies to generate a bivalent EIV live-attenuated influenza vaccine (LAIV). We combined our previously described clade 1 EIV LAIV A/equine/Ohio/2003 H3N8 (Ohio/03 LAIV) with a newly generated clade 2 EIV LAIV that contains the six internal genes of Ohio/03 LAIV and the HA and NA of A/equine/Richmond/1/2007 H3N8 (Rich/07 LAIV). The safety profile, immunogenicity, and protection efficacy of this bivalent EIV LAIV was tested in the natural host, horses. Vaccination of horses with the bivalent EIV LAIV, following a prime-boost regimen, was safe and able to confer protection against challenge with clade 1 (A/equine/Kentucky/2014 H3N8) and clade 2 (A/equine/Richmond/2007) wild-type (WT) EIVs, as evidenced by a reduction of clinical signs, fever, and virus excretion. This is the first description of a bivalent LAIV for the prevention of EIV in horses that follows OIE recommendations. In addition, since our bivalent EIV LAIV is based on the use of reverse genetics approaches, our results demonstrate the feasibility of using the backbone of clade 1 Ohio/03 LAIV as a master donor virus (MDV) for the production and rapid update of LAIVs for the control and protection against other EIV strains of epidemiological relevance to horses. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessArticle
Virus Adaptation and Selection Following Challenge of Animals Vaccinated against Classical Swine Fever Virus
Viruses 2019, 11(10), 932; https://doi.org/10.3390/v11100932 - 10 Oct 2019
Viewed by 197
Abstract
Vaccines against classical swine fever have proven very effective in protecting pigs from this deadly disease. However, little is known about how vaccination impacts the selective pressures acting on the classical swine fever virus (CSFV). Here we use high-throughput sequencing of viral genomes [...] Read more.
Vaccines against classical swine fever have proven very effective in protecting pigs from this deadly disease. However, little is known about how vaccination impacts the selective pressures acting on the classical swine fever virus (CSFV). Here we use high-throughput sequencing of viral genomes to investigate evolutionary changes in virus populations following the challenge of naïve and vaccinated pigs with the highly virulent CSFV strain “Koslov”. The challenge inoculum contained an ensemble of closely related viral sequences, with three major haplotypes being present, termed A, B, and C. After the challenge, the viral haplotype A was preferentially located within the tonsils of naïve animals but was highly prevalent in the sera of all vaccinated animals. We find that the viral population structure in naïve pigs after infection is very similar to that in the original inoculum. In contrast, the viral population in vaccinated pigs, which only underwent transient low-level viremia, displayed several distinct changes including the emergence of 16 unique non-synonymous single nucleotide polymorphisms (SNPs) that were not detectable in the challenge inoculum. Further analysis showed a significant loss of heterogeneity and an increasing positive selection acting on the virus populations in the vaccinated pigs. We conclude that vaccination imposes a strong selective pressure on viruses that subsequently replicate within the vaccinated animal. Full article
(This article belongs to the Section Animal Viruses)
Open AccessArticle
Eco-Epidemiological Profile and Molecular Characterization of Simian Foamy Virus in a Recently-Captured Invasive Population of Leontopithecus chrysomelas (Golden-Headed Lion Tamarin) in Rio de Janeiro, Brazil
Viruses 2019, 11(10), 931; https://doi.org/10.3390/v11100931 - 10 Oct 2019
Viewed by 138
Abstract
Simian foamy viruses (SFV) infect a wide range of Old World and Neotropical primates (NP). Unlike Old World primates, little is known about the diversity and prevalence of SFV in NP, mainly from a free-living population. Phylogenetic analyses have shown that SFV coevolved [...] Read more.
Simian foamy viruses (SFV) infect a wide range of Old World and Neotropical primates (NP). Unlike Old World primates, little is known about the diversity and prevalence of SFV in NP, mainly from a free-living population. Phylogenetic analyses have shown that SFV coevolved with their hosts. However, viral strains infecting Leontopithecus chrysomelas did not behave as expected for this hypothesis. The purpose of this study was to determine the eco-epidemiological profile and molecular characterization of SFV in a recently captured invasive population of L. chrysomelas located in Niteroi/RJ using buccal swab as an alternative collection method. A prevalence of 34.8% (32/92) and a mean viral load of 4.7 log copies of SFV/106 cells were observed. With respect to time since capture, SFV prevalence was significantly higher in the group of animals sampled over 6 months after capture (55.2%) than in those more recently captured (25.4%) (p = 0.005). Infected solitary animals can contribute to SFV transmission between different groups in the population. SFV strains formed two distinct clades within the SFV infecting the Cebidae family. This is the first study to use buccal swabs as a tool to study SFV diversity and prevalence in a recently free-living NP population upon recent capture. Full article
(This article belongs to the Special Issue Spumaretroviruses)
Open AccessArticle
Novel Polyomaviruses in Mammals from Multiple Orders and Reassessment of Polyomavirus Evolution and Taxonomy
Viruses 2019, 11(10), 930; https://doi.org/10.3390/v11100930 - 10 Oct 2019
Viewed by 189
Abstract
As the phylogenetic organization of mammalian polyomaviruses is complex and currently incompletely resolved, we aimed at a deeper insight into their evolution by identifying polyomaviruses in host orders and families that have either rarely or not been studied. Sixteen unknown and two known [...] Read more.
As the phylogenetic organization of mammalian polyomaviruses is complex and currently incompletely resolved, we aimed at a deeper insight into their evolution by identifying polyomaviruses in host orders and families that have either rarely or not been studied. Sixteen unknown and two known polyomaviruses were identified in animals that belong to 5 orders, 16 genera, and 16 species. From 11 novel polyomaviruses, full genomes could be determined. Splice sites were predicted for large and small T antigen (LTAg, STAg) coding sequences (CDS) and examined experimentally in transfected cell culture. In addition, splice sites of seven published polyomaviruses were analyzed. Based on these data, LTAg and STAg annotations were corrected for 10/86 and 74/86 published polyomaviruses, respectively. For 25 polyomaviruses, a spliced middle T CDS was observed or predicted. Splice sites that likely indicate expression of additional, alternative T antigens, were experimentally detected for six polyomaviruses. In contrast to all other mammalian polyomaviruses, three closely related cetartiodactyl polyomaviruses display two introns within their LTAg CDS. In addition, the VP2 of Glis glis (edible dormouse) polyomavirus 1 was observed to be encoded by a spliced transcript, a unique experimental finding within the Polyomaviridae family. Co-phylogenetic analyses based on LTAg CDS revealed a measurable signal of codivergence when considering all mammalian polyomaviruses, most likely driven by relatively recent codivergence events. Lineage duplication was the only other process whose influence on polyomavirus evolution was unambiguous. Finally, our analyses suggest that an update of the taxonomy of the family is required, including the creation of novel genera of mammalian and non-mammalian polyomaviruses. Full article
(This article belongs to the Section Animal Viruses)
Open AccessReview
Flavivirus RNA-Dependent RNA Polymerase Interacts with Genome UTRs and Viral Proteins to Facilitate Flavivirus RNA Replication
Viruses 2019, 11(10), 929; https://doi.org/10.3390/v11100929 - 10 Oct 2019
Viewed by 171
Abstract
Flaviviruses, most of which are emerging and re-emerging human pathogens and significant public health concerns worldwide, are positive-sense RNA viruses. Flavivirus replication occurs on the ER and is regulated by many mechanisms and factors. NS5, which consists of a C-terminal RdRp domain [...] Read more.
Flaviviruses, most of which are emerging and re-emerging human pathogens and significant public health concerns worldwide, are positive-sense RNA viruses. Flavivirus replication occurs on the ER and is regulated by many mechanisms and factors. NS5, which consists of a C-terminal RdRp domain and an N-terminal methyltransferase domain, plays a pivotal role in genome replication and capping. The C-terminal RdRp domain acts as the polymerase for RNA synthesis and cooperates with diverse viral proteins to facilitate productive RNA proliferation within the replication complex. Here, we provide an overview of the current knowledge of the functions and characteristics of the RdRp, including the subcellular localization of NS5, as well as the network of interactions formed between the RdRp and genome UTRs, NS3, and the methyltransferase domain. We posit that a detailed understanding of RdRp functions may provide a target for antiviral drug discovery and therapeutics. Full article
(This article belongs to the Special Issue Flavivirus Replication and Pathogenesis)
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Open AccessArticle
Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines
Viruses 2019, 11(10), 928; https://doi.org/10.3390/v11100928 - 10 Oct 2019
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Abstract
Influenza viruses cause annual, seasonal infection across the globe. Vaccination represents the most effective strategy to prevent such infections and/or to reduce viral disease. Two major types of influenza vaccines are approved for human use: inactivated influenza vaccines (IIVs) and live attenuated influenza [...] Read more.
Influenza viruses cause annual, seasonal infection across the globe. Vaccination represents the most effective strategy to prevent such infections and/or to reduce viral disease. Two major types of influenza vaccines are approved for human use: inactivated influenza vaccines (IIVs) and live attenuated influenza vaccines (LAIVs). Two Master Donor Virus (MDV) backbones have been used to create LAIVs against influenza A virus (IAV): the United States (US) A/Ann Arbor/6/60 (AA) and the Russian A/Leningrad/134/17/57 (Len) H2N2 viruses. The mutations responsible for the temperature sensitive (ts), cold-adapted (ca) and attenuated (att) phenotypes of the two MDVs have been previously identified and genetically mapped. However, a direct comparison of the contribution of these residues to viral attenuation, immunogenicity and protection efficacy has not been conducted. Here, we compared the In vitro and in vivo phenotype of recombinant influenza A/Puerto Rico/8/34 H1N1 (PR8) viruses containing the ts, ca and att mutations of the US (PR8/AA) and the Russian (PR8/Len) MDVs. Our results show that PR8/Len is more attenuated in vivo than PR8/AA, although both viruses induced similar levels of humoral and cellular responses, and protection against homologous and heterologous viral challenges. Our findings support the feasibility of using a different virus backbone as MDV for the development of improved LAIVs for the prevention of IAV infections. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessArticle
Characterization of Three Novel Viruses from the Families Nyamiviridae, Orthomyxoviridae, and Peribunyaviridae, Isolated from Dead Birds Collected during West Nile Virus Surveillance in Harris County, Texas
Viruses 2019, 11(10), 927; https://doi.org/10.3390/v11100927 - 10 Oct 2019
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Abstract
This report describes and characterizes three novel RNA viruses isolated from dead birds collected during West Nile virus surveillance in Harris County, TX, USA (the Houston metropolitan area). The novel viruses are identified as members of the families Nyamaviridae, Orthomyxoviridae, and [...] Read more.
This report describes and characterizes three novel RNA viruses isolated from dead birds collected during West Nile virus surveillance in Harris County, TX, USA (the Houston metropolitan area). The novel viruses are identified as members of the families Nyamaviridae, Orthomyxoviridae, and Peribunyaviridae and have been designated as San Jacinto virus, Mason Creek virus, and Buffalo Bayou virus, respectively. Their potential public health and/or veterinary importance are still unknown. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
High Resolution Analysis of Respiratory Syncytial Virus Infection In Vivo
Viruses 2019, 11(10), 926; https://doi.org/10.3390/v11100926 - 10 Oct 2019
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Abstract
Human respiratory syncytial virus (HRSV) is a major cause of pediatric infection and also causes disease in the elderly and those with underlying respiratory problems. There is no vaccine for HRSV and anti-viral therapeutics are not broadly applicable. To investigate the effect of [...] Read more.
Human respiratory syncytial virus (HRSV) is a major cause of pediatric infection and also causes disease in the elderly and those with underlying respiratory problems. There is no vaccine for HRSV and anti-viral therapeutics are not broadly applicable. To investigate the effect of HRSV biology in children, nasopharyngeal aspirates were taken from children with different viral loads and a combined high throughput RNAseq and label free quantitative proteomics approach was used to characterize the nucleic acid and proteins in these samples. HRSV proteins were identified in the nasopharyngeal aspirates from infected children, and their abundance correlated with viral load (Ct value), confirming HRSV infection. Analysis of the HRSV genome indicated that the children were infected with sub-group A virus and that minor variants in nucleotide frequency occurred in discrete clusters along the HRSV genome, and within a patient clustered distinctly within the glycoprotein gene. Data from the samples were binned into four groups; no-HRSV infection (control), high viral load (Ct < 20), medium viral load (Ct = 20–25), and low viral load (Ct > 25). Cellular proteins associated with the anti-viral response (e.g., ISG15) were identified in the nasopharyngeal aspirates and their abundance was correlated with viral load. These combined approaches have not been used before to study HRSV biology in vivo and can be readily applied to the study the variation of virus host interactions. Full article
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Open AccessArticle
Genome Analysis of a Novel Clade II.b Alphabaculovirus Obtained from Artaxa digramma
Viruses 2019, 11(10), 925; https://doi.org/10.3390/v11100925 - 09 Oct 2019
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Abstract
Artaxa digramma is a lepidopteran pest distributed throughout southern China, Myanmar, Indonesia, and India. Artaxa digramma nucleopolyhedrovirus (ArdiNPV) is a specific viral pathogen of A. digramma and deemed as a promising biocontrol agent against the pest. In this study, the complete genome sequence [...] Read more.
Artaxa digramma is a lepidopteran pest distributed throughout southern China, Myanmar, Indonesia, and India. Artaxa digramma nucleopolyhedrovirus (ArdiNPV) is a specific viral pathogen of A. digramma and deemed as a promising biocontrol agent against the pest. In this study, the complete genome sequence of ArdiNPV was determined by deep sequencing. The genome of ArdiNPV contains a double-stranded DNA (dsDNA) of 161,734 bp in length and 39.1% G+C content. Further, 149 hypothetical open reading frames (ORFs) were predicted to encode proteins >50 amino acids in length, covering 83% of the whole genome. Among these ORFs, 38 were baculovirus core genes, 22 were lepidopteran baculovirus conserved genes, and seven were unique to ArdiNPV, respectively. No typical baculoviral homologous regions (hrs) were identified in the genome. ArdiNPV had five multi-copy genes including baculovirus repeated ORFs (bros), calcium/sodium antiporter B (chaB), DNA binding protein (dbp), inhibitor of apoptosis protein (iap), and p26. Interestingly, phylogenetic analyses showed that ArdiNPV belonged to Clade II.b of Group II Alphabaculoviruses, which all contain a second copy of dbp. The genome of ArdiNPV was the closest to Euproctis pseudoconspersa nucleopolyhedrovirus, with 57.4% whole-genome similarity. Therefore, these results suggest that ArdiNPV is a novel baculovirus belonging to a newly identified cluster of Clade II.b Alphabaculoviruses. Full article
(This article belongs to the Special Issue Insect Viruses and Pest Management)
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Open AccessArticle
Differential Susceptibility and Innate Immune Response of Aedes aegypti and Aedes albopictus to the Haitian Strain of the Mayaro Virus
Viruses 2019, 11(10), 924; https://doi.org/10.3390/v11100924 - 09 Oct 2019
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Abstract
Mayaro (MAYV) is an emerging arthropod-borne virus belonging to the Alphavirus genus of the Togaviridae family. Although forest-dwelling Haemagogus mosquitoes have been considered as its main vector, the virus has also been detected in circulating Aedes ssp mosquitoes. Here we assess the susceptibility [...] Read more.
Mayaro (MAYV) is an emerging arthropod-borne virus belonging to the Alphavirus genus of the Togaviridae family. Although forest-dwelling Haemagogus mosquitoes have been considered as its main vector, the virus has also been detected in circulating Aedes ssp mosquitoes. Here we assess the susceptibility of Aedes aegypti and Aedes albopictus to infection with MAYV and their innate immune response at an early stage of infection. Aedes albopictus was more susceptible to infection with MAYV than Ae. aegypti. Analysis of transcript levels of twenty immunity-related genes by real-time PCR in the midgut of both mosquitoes infected with MAYV revealed increased expression of several immune genes, including CLIP-domain serine proteases, the anti-microbial peptides defensin A, E, cecropin E, and the virus inducible gene. The regulation of certain genes appeared to be Aedes species-dependent. Infection of Ae. aegypti with MAYV resulted in increased levels of myeloid differentiation2-related lipid recognition protein (ML26A) transcripts, as compared to Ae. albopictus. Increased expression levels of thio-ester-containing protein 22 (TEP22) and Niemann–Pick type C1 (NPC1) gene transcripts were observed in infected Ae. albopictus, but not Ae. aegypti. The differences in these gene expression levels during MAYV infection could explain the variation in susceptibility observed in both mosquito species. Full article
(This article belongs to the Special Issue Emerging Arboviruses)
Open AccessArticle
Novel Mutations Evading Avian Immunity around the Receptor Binding Site of the Clade 2.3.2.1c Hemagglutinin Gene Reduce Viral Thermostability and Mammalian Pathogenicity
Viruses 2019, 11(10), 923; https://doi.org/10.3390/v11100923 - 09 Oct 2019
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Abstract
Abstract: Since 2007, highly pathogenic clade 2.3.2 H5N1 avian influenza A (A(H5N1)) viruses have evolved to clade 2.3.2.1a, b, and c; currently only 2.3.2.1c A(H5N1) viruses circulate in wild birds and poultry. During antigenic evolution, clade 2.3.2.1a and c A(H5N1) viruses [...] Read more.
Abstract: Since 2007, highly pathogenic clade 2.3.2 H5N1 avian influenza A (A(H5N1)) viruses have evolved to clade 2.3.2.1a, b, and c; currently only 2.3.2.1c A(H5N1) viruses circulate in wild birds and poultry. During antigenic evolution, clade 2.3.2.1a and c A(H5N1) viruses acquired both S144N and V223I mutations around the receptor binding site of hemagglutinin (HA), with S144N generating an N-glycosylation sequon. We introduced single or combined reverse mutations, N144S and/or I223V, into the HA gene of the clade 2.3.2.1c A(H5N1) virus and generated PR8-derived, 2 + 6 recombinant A(H5N1) viruses. When we compared replication efficiency in embryonated chicken eggs, mammalian cells, and mice, the recombinant virus containing both N144S and I223V mutations showed increased replication efficiency in avian and mammalian hosts and pathogenicity in mice. The N144S mutation significantly decreased avian receptor affinity and egg white inhibition, but not all mutations increased mammalian receptor affinity. Interestingly, the combined reverse mutations dramatically increased the thermostability of HA. Therefore, the adaptive mutations possibly acquired to evade avian immunity may decrease viral thermostability as well as mammalian pathogenicity. Full article
(This article belongs to the Section Animal Viruses)
Open AccessReview
A Current Update on Human Papillomavirus-Associated Head and Neck Cancers
Viruses 2019, 11(10), 922; https://doi.org/10.3390/v11100922 - 09 Oct 2019
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Abstract
Human papillomavirus (HPV) infection is the cause of a growing percentage of head and neck cancers (HNC); primarily, a subset of oral squamous cell carcinoma, oropharyngeal squamous cell carcinoma, and laryngeal squamous cell carcinoma. The majority of HPV-associated head and neck cancers (HPV [...] Read more.
Human papillomavirus (HPV) infection is the cause of a growing percentage of head and neck cancers (HNC); primarily, a subset of oral squamous cell carcinoma, oropharyngeal squamous cell carcinoma, and laryngeal squamous cell carcinoma. The majority of HPV-associated head and neck cancers (HPV + HNC) are caused by HPV16; additionally, co-factors such as smoking and immunosuppression contribute to the progression of HPV + HNC by interfering with tumor suppressor miRNA and impairing mediators of the immune system. This review summarizes current studies on HPV + HNC, ranging from potential modes of oral transmission of HPV (sexual, self-inoculation, vertical and horizontal transmissions), discrepancy in the distribution of HPV + HNC between anatomical sites in the head and neck region, and to studies showing that HPV vaccines have the potential to protect against oral HPV infection (especially against the HPV types included in the vaccines). The review concludes with a discussion of major challenges in the field and prospects for the future: challenges in diagnosing HPV + HNC at early stages of the disease, measures to reduce discrepancy in the prevalence of HPV + HNC cases between anatomical sites, and suggestions to assess whether fomites/breast milk can transmit HPV to the oral cavity. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Interferon γ and α Have Differential Effects on SAMHD1, a Potent Antiviral Protein, in Feline Lymphocytes
Viruses 2019, 11(10), 921; https://doi.org/10.3390/v11100921 - 09 Oct 2019
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Abstract
Sterile alpha motif and histidine/aspartic domain-containing protein 1 (SAMHD1) is a protein with anti-viral, anti-neoplastic, and anti-inflammatory properties. By degrading cellular dNTPs to constituent deoxynucleoside and free triphosphate, SAMHD1 limits viral DNA synthesis and prevents replication of HIV-1 and some DNA viruses such [...] Read more.
Sterile alpha motif and histidine/aspartic domain-containing protein 1 (SAMHD1) is a protein with anti-viral, anti-neoplastic, and anti-inflammatory properties. By degrading cellular dNTPs to constituent deoxynucleoside and free triphosphate, SAMHD1 limits viral DNA synthesis and prevents replication of HIV-1 and some DNA viruses such as HBV, vaccinia, and HSV-1. Recent findings suggest SAMHD1 is broadly active against retroviruses in addition to HIV-1, such as HIV-2, FIV, BIV, and EIAV. Interferons are cytokines produced by lymphocytes and other cells that induce a wide array of antiviral proteins, including some with activity again lentiviruses. Here we evaluated the role of IFNs on SAMHD1 gene expression, transcription, and post-translational modification in a feline CD4+ T cell line (FeTJ) and in primary feline CD4+ T lymphocytes. SAMHD1 mRNA in FetJ cells increased in a dose-related manner in response to IFNγ treatment concurrent with increased nuclear localization and phosphorylation. IFNα treatment induced SAMHD1 mRNA but did not significantly alter SAMHD1 protein detection, phosphorylation, or nuclear translocation. In purified primary feline CD4+ lymphocytes, IL2 supplementation increased SAMHD1 expression, but the addition of IFNγ did not further alter SAMHD1 protein expression or nuclear localization. Thus, the effect of IFNγ on SAMHD1 expression is cell-type dependent, with increased translocation to the nucleus and phosphorylation in FeTJ but not primary CD4+ lymphocytes. These findings imply that while SAMH1 is inducible by IFNγ, overall activity is cell type and compartment specific, which is likely relevant to the establishment of lentiviral reservoirs in quiescent lymphocyte populations. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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Open AccessArticle
Internal Ribosome Entry Site Dramatically Reduces Transgene Expression in Hematopoietic Cells in a Position-Dependent Manner
Viruses 2019, 11(10), 920; https://doi.org/10.3390/v11100920 - 08 Oct 2019
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Abstract
Bicistronic transgene expression mediated by internal ribosome entry site (IRES) elements has been widely used. It co-expresses heterologous transgene products from a message RNA driven by a single promoter. Hematologic gene delivery is a promising treatment for both inherited and acquired diseases. A [...] Read more.
Bicistronic transgene expression mediated by internal ribosome entry site (IRES) elements has been widely used. It co-expresses heterologous transgene products from a message RNA driven by a single promoter. Hematologic gene delivery is a promising treatment for both inherited and acquired diseases. A combined strategy was recently documented for potential genome editing in hematopoietic cells. A transduction efficiency exceeding ~90% can be achieved by capsid-optimized recombinant adeno-associated virus serotype 6 (rAAV6) vectors. In this study, to deliver an encephalomyocarditis virus (EMCV) IRES-containing rAAV6 genome into hematopoietic cells, we observed that EMCV IRES almost completely shut down the transgene expression during the process of mRNA–protein transition. In addition, position-dependent behavior was observed, in which only the EMCV IRES element located between a promoter and the transgenes had an inhibitory effect. Although further studies are warranted to evaluate the involvement of cellular translation machinery, our results propose the use of specific IRES elements or an alternative strategy, such as the 2A system, to achieve bicistronic transgene expression in hematopoietic cells. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism)
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Open AccessArticle
Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice
Viruses 2019, 11(10), 919; https://doi.org/10.3390/v11100919 - 08 Oct 2019
Viewed by 261
Abstract
Rift Valley fever virus (RVFV), which causes Rift Valley fever (RVF), is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. RVF is a World Health Organization (WHO) priority disease and, together with rabies, is a major health [...] Read more.
Rift Valley fever virus (RVFV), which causes Rift Valley fever (RVF), is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. RVF is a World Health Organization (WHO) priority disease and, together with rabies, is a major health burden in Africa. Here, we present the development and characterization of an inactivated recombinant RVFV and rabies virus (RABV) vaccine candidate (rSRV9-eGn). Immunization with rSRV9-eGn stimulated the production of RVFV-specific IgG antibodies and induced humoral and cellular immunity in mice but did not induce the production of neutralizing antibodies. IgG1 and IgG2a were the main isotypes observed by IgG subtype detection, and IgG3 antibodies were not detected. The ratios of IgG1/IgG2a > 1 indicated a Type 2 humoral immune response. An effective vaccine is intended to establish a long-lived population of memory T cells, and mice generated memory cells among the proliferating T cell population after immunization with rSRV9-eGn, with effector memory T cells (TEM) as the major population. Due to the lack of prophylactic treatment experiments, it is impossible to predict whether this vaccine can protect animals from RVFV infection with only high titres of anti-RVFV IgG antibodies and no neutralizing antibodies induced, and thus, protection confirmation needs further verification. However, this RVFV vaccine designed with RABV as the vector provides ideas for the development of vaccines that prevent RVFV and RABV infections. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessArticle
Peste des Petits Ruminants Virus-Like Particles Induce a Potent Humoral and Cellular Immune Response in Goats
Viruses 2019, 11(10), 918; https://doi.org/10.3390/v11100918 - 05 Oct 2019
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Abstract
Peste des petits ruminants is a highly contagious acute or subacute disease of small ruminants caused by the peste des petits ruminants virus (PPRV), and it is responsible for significant economic losses in animal husbandry. Vaccination represents the most effective means of controlling [...] Read more.
Peste des petits ruminants is a highly contagious acute or subacute disease of small ruminants caused by the peste des petits ruminants virus (PPRV), and it is responsible for significant economic losses in animal husbandry. Vaccination represents the most effective means of controlling this disease, with virus-like particle (VLP) vaccines offering promising vaccine candidates. In this study, a PPRV VLP-based vaccine was developed using a baculovirus expression system, allowing for the simultaneous expression of the PPRV matrix (M), hemagglutinin (H), fusion (F) and nucleocapsid (N) proteins in insect cells. Immunization of mice and goats with PPRV VLPs elicited a robust neutralization response and a potent cellular immune response. Mouse studies demonstrated that VLPs induced a more robust IFN-γ response in CD4+ and CD8+ T cells than PPRV Nigeria 75/1 and recruited and/or activated more B cells and dendritic cells in inguinal lymph nodes. In addition, PPRV VLPs induced a strong Th1 class response in mice, as indicated by a high IgG2a to IgG1 ratio. Goat studies demonstrated that PPRV VLPs can induce the production of antibodies specific for F and H proteins and can also stimulate the production of virus neutralizing antibodies to the same magnitude as the PPRV Nigeria 75/1 vaccine. Higher amounts of IFN-γ in VLP-immunized animal serum suggested that VLPs also elicited a cellular immune response in goats. These results demonstrated that VLPs elicit a potent immune response against PPRV infection in small ruminants, making PPRV VLPs a potential candidate for PPRV vaccine development. Full article
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