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Viruses, Volume 9, Issue 6 (June 2017)

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Cover Story (view full-size image) Thus far, little is known about Arctic algal viruses. Basic characterization of new dsDNA [...] Read more.
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Open AccessArticle
Co-Infection with Marek’s Disease Virus and Reticuloendotheliosis Virus Increases Illness Severity and Reduces Marek’s Disease Vaccine Efficacy
Viruses 2017, 9(6), 158; https://doi.org/10.3390/v9060158
Received: 25 April 2017 / Revised: 19 June 2017 / Accepted: 20 June 2017 / Published: 21 June 2017
Cited by 4 | Viewed by 2143 | PDF Full-text (5426 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Marek’s disease virus (MDV) and reticuloendotheliosis virus (REV) cause Marek’s disease (MD) and reticuloendotheliosis (RE), respectively. Co-infection with MDV and REV is common in chickens, causing serious losses to the poultry industry. However, experimental studies of such co-infection are lacking. In this study, [...] Read more.
Marek’s disease virus (MDV) and reticuloendotheliosis virus (REV) cause Marek’s disease (MD) and reticuloendotheliosis (RE), respectively. Co-infection with MDV and REV is common in chickens, causing serious losses to the poultry industry. However, experimental studies of such co-infection are lacking. In this study, Chinese field strains of MDV (ZW/15) and REV (JLR1501) were used as challenge viruses to evaluate the pathogenicity of co-infection and the influence of MD vaccination in chickens. Compared to the MDV-challenged group, the mortality and tumor rates increased significantly by 20.0% (76.7 to 96.7%) and 26.7% (53.3 to 80.0%), in the co-challenged group, respectively. The protective index of the MD vaccines CVI988 and 814 decreased by 33.3 (80.0 to 47.7) and 13.3 (90.0 to 76.7), respectively. These results indicated that MDV and REV co-infection significantly increased disease severity and reduced the vaccine efficacy. The MDV genome load showed no difference in the feather pulps and spleen, and pathogenicity-related MDV gene expression (meq, pp38, vIL-8, and ICP4) in the spleen significantly increased at some time points in the co-challenged group. Clearly, synergistic pathogenicity occurred between MDV and REV, and the protective efficacy of existing MD vaccines was attenuated by co-infection with Chinese field MDV and REV strains. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessArticle
Rab33B Controls Hepatitis B Virus Assembly by Regulating Core Membrane Association and Nucleocapsid Processing
Viruses 2017, 9(6), 157; https://doi.org/10.3390/v9060157
Received: 26 January 2017 / Revised: 9 June 2017 / Accepted: 14 June 2017 / Published: 21 June 2017
Cited by 3 | Viewed by 1982 | PDF Full-text (6686 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Many viruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Using RNA interference (RNAi), we demonstrate that the Golgi/autophagosome-associated Rab33B is required for hepatitis B virus (HBV) propagation in hepatoma cell lines. While Rab33B is dispensable for the [...] Read more.
Many viruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Using RNA interference (RNAi), we demonstrate that the Golgi/autophagosome-associated Rab33B is required for hepatitis B virus (HBV) propagation in hepatoma cell lines. While Rab33B is dispensable for the secretion of HBV subviral envelope particles, its knockdown reduced the virus yield to 20% and inhibited nucleocapsid (NC) formation and/or NC trafficking. The overexpression of a GDP-restricted Rab33B mutant phenocopied the effect of deficit Rab33B, indicating that Rab33B-specific effector proteins may be involved. Moreover, we found that HBV replication enhanced Rab33B expression. By analyzing HBV infection cycle steps, we identified a hitherto unknown membrane targeting module in the highly basic C-terminal domain of the NC-forming core protein. Rab33B inactivation reduced core membrane association, suggesting that membrane platforms participate in HBV assembly reactions. Biochemical and immunofluorescence analyses provided further hints that the viral core, rather than the envelope, is the main target for Rab33B intervention. Rab33B-deficiency reduced core protein levels without affecting viral transcription and hampered core/NC sorting to envelope-positive, intracellular compartments. Together, these results indicate that Rab33B is an important player in intracellular HBV trafficking events, guiding core transport to NC assembly sites and/or NC transport to budding sites. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessFeature PaperReview
The Role of cccDNA in HBV Maintenance
Viruses 2017, 9(6), 156; https://doi.org/10.3390/v9060156
Received: 4 May 2017 / Revised: 16 June 2017 / Accepted: 19 June 2017 / Published: 21 June 2017
Cited by 26 | Viewed by 2887 | PDF Full-text (343 KB) | HTML Full-text | XML Full-text
Abstract
Chronic hepatitis B virus (HBV) infection continues to be a major health burden worldwide; it can cause various degrees of liver damage and is strongly associated with the development of liver cirrhosis and hepatocellular carcinoma. The molecular mechanisms determining HBV persistence are not [...] Read more.
Chronic hepatitis B virus (HBV) infection continues to be a major health burden worldwide; it can cause various degrees of liver damage and is strongly associated with the development of liver cirrhosis and hepatocellular carcinoma. The molecular mechanisms determining HBV persistence are not fully understood, but these appear to be multifactorial and the unique replication strategy employed by HBV enables its maintenance in infected hepatocytes. Both the stability of the HBV genome, which forms a stable minichromosome, the covalently closed circular DNA (cccDNA) in the hepatocyte nucleus, and the inability of the immune system to resolve chronic HBV infection are believed to be key mechanisms of HBV chronicity. Since a true cure of HBV requires clearance of intranuclear cccDNA from infected hepatocytes, understanding the mechanisms involved in cccDNA biogenesis, regulation and stability is mandatory to achieve HBV eradication. This review will summarize the state of knowledge on these mechanisms including the impact of current treatments on the cccDNA stability and activity. We will focus on events challenging cccDNA persistence in dividing hepatocytes. Full article
(This article belongs to the Special Issue Recent Advances in Hepatitis B Virus Research)
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Open AccessArticle
Host Adaptation of Soybean Dwarf Virus Following Serial Passages on Pea (Pisum sativum) and Soybean (Glycine max)
Viruses 2017, 9(6), 155; https://doi.org/10.3390/v9060155
Received: 26 May 2017 / Revised: 15 June 2017 / Accepted: 16 June 2017 / Published: 21 June 2017
Cited by 1 | Viewed by 1929 | PDF Full-text (1855 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Soybean Dwarf Virus (SbDV) is an important plant pathogen, causing economic losses in soybean. In North America, indigenous strains of SbDV mainly infect clover, with occasional outbreaks in soybean. To evaluate the risk of a US clover strain of SbDV adapting to other [...] Read more.
Soybean Dwarf Virus (SbDV) is an important plant pathogen, causing economic losses in soybean. In North America, indigenous strains of SbDV mainly infect clover, with occasional outbreaks in soybean. To evaluate the risk of a US clover strain of SbDV adapting to other plant hosts, the clover isolate SbDV-MD6 was serially transmitted to pea and soybean by aphid vectors. Sequence analysis of SbDV-MD6 from pea and soybean passages identified 11 non-synonymous mutations in soybean, and six mutations in pea. Increasing virus titers with each sequential transmission indicated that SbDV-MD6 was able to adapt to the plant host. However, aphid transmission efficiency on soybean decreased until the virus was no longer transmissible. Our results clearly demonstrated that the clover strain of SbDV-MD6 is able to adapt to soybean crops. However, mutations that improve replication and/or movement may have trade-off effects resulting in decreased vector transmission. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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Open AccessReview
A Review of Flaviviruses that Have No Known Arthropod Vector
Viruses 2017, 9(6), 154; https://doi.org/10.3390/v9060154
Received: 16 May 2017 / Revised: 15 June 2017 / Accepted: 16 June 2017 / Published: 21 June 2017
Cited by 10 | Viewed by 2494 | PDF Full-text (2775 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Most viruses in the genus Flavivirus are horizontally transmitted between hematophagous arthropods and vertebrate hosts, but some are maintained in arthropod- or vertebrate-restricted transmission cycles. Flaviviruses maintained by vertebrate-only transmission are commonly referred to as no known vector (NKV) flaviviruses. Fourteen species and [...] Read more.
Most viruses in the genus Flavivirus are horizontally transmitted between hematophagous arthropods and vertebrate hosts, but some are maintained in arthropod- or vertebrate-restricted transmission cycles. Flaviviruses maintained by vertebrate-only transmission are commonly referred to as no known vector (NKV) flaviviruses. Fourteen species and two subtypes of NKV flaviviruses are recognized by the International Committee on Taxonomy of Viruses (ICTV), and Tamana bat virus potentially belongs to this group. NKV flaviviruses have been isolated in nature almost exclusively from bats and rodents; exceptions are the two isolates of Dakar bat virus recovered from febrile humans and the recent isolations of Sokoluk virus from field-collected ticks, which raises questions as to whether it should remain classified as an NKV flavivirus. There is evidence to suggest that two other NKV flaviviruses, Entebbe bat virus and Yokose virus, may also infect arthropods in nature. The best characterized bat- and rodent-associated NKV flaviviruses are Rio Bravo and Modoc viruses, respectively, but both have received limited research attention compared to many of their arthropod-infecting counterparts. Herein, we provide a comprehensive review of NKV flaviviruses, placing a particular emphasis on their classification, host range, geographic distribution, replication kinetics, pathogenesis, transmissibility and molecular biology. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessReview
Modulation of Human β-Defensin-1 Production by Viruses
Viruses 2017, 9(6), 153; https://doi.org/10.3390/v9060153
Received: 1 May 2017 / Revised: 13 June 2017 / Accepted: 16 June 2017 / Published: 21 June 2017
Cited by 4 | Viewed by 1583 | PDF Full-text (848 KB) | HTML Full-text | XML Full-text
Abstract
While initially identified as a broad-spectrum antimicrobial peptide, constitutively expressed in epithelia, human β-defensin (hBD)-1 is now recognized to have a more complex pattern of expression of its gene, DEFB1, as well as activities that extend beyond direct antimicrobial. These observations suggest [...] Read more.
While initially identified as a broad-spectrum antimicrobial peptide, constitutively expressed in epithelia, human β-defensin (hBD)-1 is now recognized to have a more complex pattern of expression of its gene, DEFB1, as well as activities that extend beyond direct antimicrobial. These observations suggest a complex role for hBD-1 in the host defense against viral infections, as evidenced by its expression in cells involved in viral defense, and its gene regulation in response to viral challenge. This regulation is observed both in vitro and in vivo in humans, as well as with the murine homolog, mBD-1. While numerous reviews have summarized the existing literature on β-defensin gene expression and activity, here we provide a focused review of relevant studies on the virus-mediated regulation of hBD-1 and how this regulation can provide a crucial aspect of the innate immune defense against viral infection. Full article
(This article belongs to the Special Issue Defensins)
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Open AccessArticle
Nutrients and Other Environmental Factors Influence Virus Abundances across Oxic and Hypoxic Marine Environments
Viruses 2017, 9(6), 152; https://doi.org/10.3390/v9060152
Received: 15 March 2017 / Revised: 10 June 2017 / Accepted: 13 June 2017 / Published: 17 June 2017
Cited by 12 | Viewed by 4429 | PDF Full-text (1224 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Virus particles are highly abundant in seawater and, on average, outnumber microbial cells approximately 10-fold at the surface and 16-fold in deeper waters; yet, this relationship varies across environments. Here, we examine the influence of a suite of environmental variables, including nutrient concentrations, [...] Read more.
Virus particles are highly abundant in seawater and, on average, outnumber microbial cells approximately 10-fold at the surface and 16-fold in deeper waters; yet, this relationship varies across environments. Here, we examine the influence of a suite of environmental variables, including nutrient concentrations, salinity and temperature, on the relationship between the abundances of viruses and prokaryotes over a broad range of spatial and temporal scales, including along a track from the Northwest Atlantic to the Northeast Pacific via the Arctic Ocean, and in the coastal waters of British Columbia, Canada. Models of varying complexity were tested and compared for best fit with the Akaike Information Criterion, and revealed that nitrogen and phosphorus concentrations, as well as prokaryote abundances, either individually or combined, had significant effects on viral abundances in all but hypoxic environments, which were only explained by a combination of physical and chemical factors. Nonetheless, multivariate models of environmental variables showed high explanatory power, matching or surpassing that of prokaryote abundance alone. Incorporating both environmental variables and prokaryote abundances into multivariate models significantly improved the explanatory power of the models, except in hypoxic environments. These findings demonstrate that environmental factors could be as important as, or even more important than, prokaryote abundance in describing viral abundance across wide-ranging marine environments Full article
(This article belongs to the Special Issue Marine Viruses 2016) Printed Edition available
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Open AccessArticle
Biophysical Mode-of-Action and Selectivity Analysis of Allosteric Inhibitors of Hepatitis C Virus (HCV) Polymerase
Viruses 2017, 9(6), 151; https://doi.org/10.3390/v9060151
Received: 15 May 2017 / Revised: 5 June 2017 / Accepted: 8 June 2017 / Published: 16 June 2017
Cited by 1 | Viewed by 1813 | PDF Full-text (7482 KB) | HTML Full-text | XML Full-text
Abstract
Allosteric inhibitors of hepatitis C virus (HCV) non-structural protein 5B (NS5B) polymerase are effective for treatment of genotype 1, although their mode of action and potential to inhibit other isolates and genotypes are not well established. We have used biophysical techniques and a [...] Read more.
Allosteric inhibitors of hepatitis C virus (HCV) non-structural protein 5B (NS5B) polymerase are effective for treatment of genotype 1, although their mode of action and potential to inhibit other isolates and genotypes are not well established. We have used biophysical techniques and a novel biosensor-based real-time polymerase assay to investigate the mode-of-action and selectivity of four inhibitors against enzyme from genotypes 1b (BK and Con1) and 3a. Two thumb inhibitors (lomibuvir and filibuvir) interacted with all three NS5B variants, although the affinities for the 3a enzyme were low. Of the two tested palm inhibitors (dasabuvir and nesbuvir), only dasabuvir interacted with the 1b variant, and nesbuvir interacted with NS5B 3a. Lomibuvir, filibuvir and dasabuvir stabilized the structure of the two 1b variants, but not the 3a enzyme. The thumb compounds interfered with the interaction between the enzyme and RNA and blocked the transition from initiation to elongation. The two allosteric inhibitor types have different inhibition mechanisms. Sequence and structure analysis revealed differences in the binding sites for 1b and 3a variants, explaining the poor effect against genotype 3a NS5B. The indirect mode-of-action needs to be considered when designing allosteric compounds. The current approach provides an efficient strategy for identifying and optimizing allosteric inhibitors targeting HCV genotype 3a. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessReview
Phage-Phagocyte Interactions and Their Implications for Phage Application as Therapeutics
Viruses 2017, 9(6), 150; https://doi.org/10.3390/v9060150
Received: 31 March 2017 / Revised: 7 June 2017 / Accepted: 7 June 2017 / Published: 14 June 2017
Cited by 13 | Viewed by 2248 | PDF Full-text (516 KB) | HTML Full-text | XML Full-text
Abstract
Phagocytes are the main component of innate immunity. They remove pathogens and particles from organisms using their bactericidal tools in the form of both reactive oxygen species and degrading enzymes—contained in granules—that are potentially toxic proteins. Therefore, it is important to investigate the [...] Read more.
Phagocytes are the main component of innate immunity. They remove pathogens and particles from organisms using their bactericidal tools in the form of both reactive oxygen species and degrading enzymes—contained in granules—that are potentially toxic proteins. Therefore, it is important to investigate the possible interactions between phages and immune cells and avoid any phage side effects on them. Recent progress in knowledge concerning the influence of phages on phagocytes is also important as such interactions may shape the immune response. In this review we have summarized the current knowledge on phage interactions with phagocytes described so far and their potential implications for phage therapy. The data suggesting that phage do not downregulate important phagocyte functions are especially relevant for the concept of phage therapy. Full article
(This article belongs to the Special Issue Viruses of Microbes)
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Open AccessArticle
Impact of Parvovirus B19 Viremia in Liver Transplanted Children on Anemia: A Retrospective Study
Viruses 2017, 9(6), 149; https://doi.org/10.3390/v9060149
Received: 5 April 2017 / Revised: 30 May 2017 / Accepted: 6 June 2017 / Published: 13 June 2017
Cited by 2 | Viewed by 1373 | PDF Full-text (689 KB) | HTML Full-text | XML Full-text
Abstract
Acute parvovirus B19 (B19V) infection in immunocompromised patients may lead to severe anemia. However, in adult transplant recipients, B19V reactivations without anemia and low-level viremia are common. The impact of B19V in pediatric transplant patients, with high risk of primary infection, is investigated [...] Read more.
Acute parvovirus B19 (B19V) infection in immunocompromised patients may lead to severe anemia. However, in adult transplant recipients, B19V reactivations without anemia and low-level viremia are common. The impact of B19V in pediatric transplant patients, with high risk of primary infection, is investigated here. In a six-month period, 159 blood samples of 54 pediatric liver transplant recipients were tested for B19V DNA by quantitative real-time PCR. Viremia was correlated with anemia and immunosuppression and compared with rates in adult transplant recipients. B19V DNA was detected in 5/54 patients. Primary B19V infections were observed in four patients prior to and in one patient after transplantation. Rates of viremia were significantly higher in pediatric recipients than in adults. Prolonged virus shedding after primary infection prior to transplantation accounts for most viremic cases. Anemia was significantly more frequent in samples from viremic patients, but remained mild. In 15% of anemic samples, B19V DNA was detected. Therefore, in anemic pediatric transplant recipients, diagnostics for B19V seem reasonable. Full article
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Open AccessReview
Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus
Viruses 2017, 9(6), 148; https://doi.org/10.3390/v9060148
Received: 31 March 2017 / Revised: 25 May 2017 / Accepted: 7 June 2017 / Published: 13 June 2017
Cited by 14 | Viewed by 2417 | PDF Full-text (805 KB) | HTML Full-text | XML Full-text
Abstract
The adaptive immune response is necessary for the development of protective immunity against infectious diseases. Porcine reproductive and respiratory syndrome virus (PRRSV), a genetically heterogeneous and rapidly evolving RNA virus, is the most burdensome pathogen of swine health and wellbeing worldwide. Viral infection [...] Read more.
The adaptive immune response is necessary for the development of protective immunity against infectious diseases. Porcine reproductive and respiratory syndrome virus (PRRSV), a genetically heterogeneous and rapidly evolving RNA virus, is the most burdensome pathogen of swine health and wellbeing worldwide. Viral infection induces antigen-specific immunity that ultimately clears the infection. However, the resulting immune memory, induced by virulent or attenuated vaccine viruses, is inconsistently protective against diverse viral strains. The immunological mechanisms by which primary and memory protection are generated and used are not well understood. Here, we summarize current knowledge regarding cellular and humoral components of the adaptive immune response to PRRSV infection that mediate primary and memory immune protection against viruses. Full article
(This article belongs to the Special Issue Porcine Viruses) Printed Edition available
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Open AccessArticle
HAdV-C6 Is a More Relevant Challenge Virus than HAdV-C5 for Testing Antiviral Drugs with the Immunosuppressed Syrian Hamster Model
Viruses 2017, 9(6), 147; https://doi.org/10.3390/v9060147
Received: 3 May 2017 / Revised: 31 May 2017 / Accepted: 5 June 2017 / Published: 13 June 2017
Cited by 2 | Viewed by 1413 | PDF Full-text (1241 KB) | HTML Full-text | XML Full-text
Abstract
Adenovirus infections of immunocompromised patients can cause a severe multi-organ disease that often results in the patients’ death. Presently, there are no drugs specifically approved to treat adenovirus infections, and clinicians resort to the off-label use of antivirals that are approved to treat [...] Read more.
Adenovirus infections of immunocompromised patients can cause a severe multi-organ disease that often results in the patients’ death. Presently, there are no drugs specifically approved to treat adenovirus infections, and clinicians resort to the off-label use of antivirals that are approved to treat other DNA virus infections, most frequently cidofovir (CDV). CDV, however, has considerable nephrotoxicity, thus it is recommended only for the most severe cases of adenovirus infections. To facilitate the development of effective, non-toxic antivirals against adenovirus, we have developed a permissive animal model based on the Syrian hamster that can be used to test the efficacy of antiviral compounds. Here, we show that in the hamster model, HAdV-C6 is a more useful challenge virus than the previously described HAdV-C5, because it is filtered out by tissue macrophages to a lesser extent. HAdV-C6 has a 10-fold lower LD50 in hamsters than HAdV-C5 and the pathology is caused by virus replication to a larger extent. We show that valganciclovir (VGCV), a drug that was shown to be active against intravenous HAdV-C5 infection previously, is efficacious against HAdV-C6 when administered either prophylactically or therapeutically. Further, we show for the first time that VGCV, and to a lesser extent CDV, can be used to treat respiratory adenovirus infections in the hamster model. These results extend the utility of the hamster model, and demonstrate the efficacy of two drugs available for clinicians to treat adenovirus infections. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessFeature PaperReview
Zika Virus: Recent Advances towards the Development of Vaccines and Therapeutics
Viruses 2017, 9(6), 143; https://doi.org/10.3390/v9060143
Received: 18 April 2017 / Revised: 2 June 2017 / Accepted: 8 June 2017 / Published: 13 June 2017
Cited by 13 | Viewed by 4427 | PDF Full-text (277 KB) | HTML Full-text | XML Full-text
Abstract
Zika is a rapidly emerging public health threat. Although clinical infection is frequently mild, significant neurological manifestations have been demonstrated in infants born to Zika virus (ZIKV) infected mothers. Due to the substantial ramifications of intrauterine infection, effective counter-measures are urgently needed. In [...] Read more.
Zika is a rapidly emerging public health threat. Although clinical infection is frequently mild, significant neurological manifestations have been demonstrated in infants born to Zika virus (ZIKV) infected mothers. Due to the substantial ramifications of intrauterine infection, effective counter-measures are urgently needed. In order to develop effective anti-ZIKV vaccines and therapeutics, improved animal models and a better understanding of immunological correlates of protection against ZIKV are required. This review will summarize what is currently known about ZIKV, the clinical manifestations and epidemiology of Zika as well as, the development of animal models to study ZIKV infection, host immune responses against ZIKV, and the current state of development of vaccines and therapeutics against ZIKV. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research) Printed Edition available
Open AccessArticle
Characterization of Bacillus subtilis Viruses vB_BsuM-Goe2 and vB_BsuM-Goe3
Viruses 2017, 9(6), 146; https://doi.org/10.3390/v9060146
Received: 27 March 2017 / Revised: 1 June 2017 / Accepted: 1 June 2017 / Published: 12 June 2017
Cited by 6 | Viewed by 1952 | PDF Full-text (5257 KB) | HTML Full-text | XML Full-text
Abstract
The Spounavirinae viruses are ubiquitous in nature and have an obligatory virulent lifestyle. They infect Firmicutes, a bacterial phylum containing an array of environmental non-pathogenic and pathogenic organisms. To expand the knowledge of this viral subfamily, new strains were isolated and investigated [...] Read more.
The Spounavirinae viruses are ubiquitous in nature and have an obligatory virulent lifestyle. They infect Firmicutes, a bacterial phylum containing an array of environmental non-pathogenic and pathogenic organisms. To expand the knowledge of this viral subfamily, new strains were isolated and investigated in this study. Here we present two new viruses, vB_BsuM-Goe2 and vB_BsuM-Goe3, isolated from raw sewage and infecting Bacillus species. Both were morphologically classified via transmission electron microscopy (TEM) as members of the Spounavirinae subfamily belonging to the Myoviridae family. Genomic sequencing and analyses allowed further affiliation of vB_BsuM-Goe2 to the SPO1-like virus group and vB_BsuM-Goe3 to the Bastille-like virus group. Experimentally determined adsorption constant, latency period, burst size and host range for both viruses revealed different survival strategies. Thus vB_BsuM-Goe2 seemed to rely on fewer host species compared to vB_BsuM-Goe3, but efficiently recruits those. Stability tests pointed out that both viruses are best preserved in LB-medium or TMK-buffer at 4 or 21 °C, whereas cryopreservation strongly reduced viability. Full article
(This article belongs to the Special Issue Viruses of Microbes)
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Open AccessArticle
Highly Sensitive Bacteriophage-Based Detection of Brucella abortus in Mixed Culture and Spiked Blood
Viruses 2017, 9(6), 144; https://doi.org/10.3390/v9060144
Received: 1 April 2017 / Revised: 25 May 2017 / Accepted: 6 June 2017 / Published: 10 June 2017
Cited by 8 | Viewed by 1894 | PDF Full-text (1834 KB) | HTML Full-text | XML Full-text
Abstract
For decades, bacteriophages (phages) have been used for Brucella species identification in the diagnosis and epidemiology of brucellosis. Traditional Brucella phage typing is a multi-day procedure including the isolation of a pure culture, a step that can take up to three weeks. In [...] Read more.
For decades, bacteriophages (phages) have been used for Brucella species identification in the diagnosis and epidemiology of brucellosis. Traditional Brucella phage typing is a multi-day procedure including the isolation of a pure culture, a step that can take up to three weeks. In this study, we focused on the use of brucellaphages for sensitive detection of the pathogen in clinical and other complex samples, and developed an indirect method of Brucella detection using real-time quantitative PCR monitoring of brucellaphage DNA amplification via replication on live Brucella cells. This assay allowed the detection of single bacteria (down to 1 colony-forming unit per milliliter) within 72 h without DNA extraction and purification steps. The technique was equally efficient with Brucella abortus pure culture and with mixed cultures of B. abortus and α-proteobacterial near neighbors that can be misidentified as Brucella spp., Ochrobactrum anthropi and Afipia felis. The addition of a simple short sample preparation step enabled the indirect phage-based detection of B. abortus in spiked blood, with the same high sensitivity. This indirect phage-based detection assay enables the rapid and sensitive detection of live B. abortus in mixed cultures and in blood samples, and can potentially be applied for detection in other clinical samples and other complex sample types. Full article
(This article belongs to the Special Issue Viruses of Microbes)
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Open AccessArticle
Classification of Cowpox Viruses into Several Distinct Clades and Identification of a Novel Lineage
Viruses 2017, 9(6), 142; https://doi.org/10.3390/v9060142
Received: 22 April 2017 / Revised: 24 May 2017 / Accepted: 5 June 2017 / Published: 10 June 2017
Cited by 17 | Viewed by 2696 | PDF Full-text (2289 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cowpox virus (CPXV) was considered as uniform species within the genus Orthopoxvirus (OPV). Previous phylogenetic analysis indicated that CPXV is polyphyletic and isolates may cluster into different clades with two of these clades showing genetic similarities to either variola (VARV) or vaccinia viruses [...] Read more.
Cowpox virus (CPXV) was considered as uniform species within the genus Orthopoxvirus (OPV). Previous phylogenetic analysis indicated that CPXV is polyphyletic and isolates may cluster into different clades with two of these clades showing genetic similarities to either variola (VARV) or vaccinia viruses (VACV). Further analyses were initiated to assess both the genetic diversity and the evolutionary background of circulating CPXVs. Here we report the full-length sequences of 20 CPXV strains isolated from different animal species and humans in Germany. A phylogenetic analysis of altogether 83 full-length OPV genomes confirmed the polyphyletic character of the species CPXV and suggested at least four different clades. The German isolates from this study mainly clustered into two CPXV-like clades, and VARV- and VACV-like strains were not observed. A single strain, isolated from a cotton-top tamarin, clustered distantly from all other CPXVs and might represent a novel and unique evolutionary lineage. The classification of CPXV strains into clades roughly followed their geographic origin, with the highest clade diversity so far observed for Germany. Furthermore, we found evidence for recombination between OPV clades without significant disruption of the observed clustering. In conclusion, this analysis markedly expands the number of available CPXV full-length sequences and confirms the co-circulation of several CPXV clades in Germany, and provides the first data about a new evolutionary CPXV lineage. Full article
(This article belongs to the Special Issue Smallpox and Emerging Zoonotic Orthopoxviruses: What Is Coming Next?)
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Open AccessFeature PaperArticle
UK Pigs at the Time of Slaughter: Investigation into the Correlation of Infection with PRRSV and HEV
Viruses 2017, 9(6), 110; https://doi.org/10.3390/v9060110
Received: 29 March 2017 / Revised: 5 May 2017 / Accepted: 6 May 2017 / Published: 9 June 2017
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Abstract
Hepatitis E virus (HEV) and porcine reproductive and respiratory syndrome virus (PRRSV) and are both globally prevalent in the pig population. While HEV does not cause clinical disease in pigs, its zoonotic potential has raised concerns in the food safety sector. PRRS has [...] Read more.
Hepatitis E virus (HEV) and porcine reproductive and respiratory syndrome virus (PRRSV) and are both globally prevalent in the pig population. While HEV does not cause clinical disease in pigs, its zoonotic potential has raised concerns in the food safety sector. PRRS has become endemic in the United Kingdom (UK) since its introduction in 1991, and continues to cause considerable economic losses to the swine industry. A better understanding of the current prevalence and diversity of PRRSV and HEV in the UK, and their potential association, is needed to assess risks and target control measures appropriately. This study used plasma, tonsil, and cecal content samples previously collected from pigs in 14 abattoirs in England and Northern Ireland to study the prevalence of several pathogens including PRRSV and HEV. The diversity of PRRSV strains detected in these samples was analyzed by sequencing open reading frame 5 (ORF5), revealing no substantial difference in PRRSV strains from these clinically unaffected pigs relative to those from clinical cases of disease in the UK. Despite the potential immuno-modulatory effect of PRRSV infection, previously demonstrated to affect Salmonella and HEV shedding profiles, no significant association was found between positive PRRSV status and positive HEV status. Full article
(This article belongs to the Special Issue Porcine Viruses) Printed Edition available
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Open AccessReview
The Human Gut Phage Community and Its Implications for Health and Disease
Viruses 2017, 9(6), 141; https://doi.org/10.3390/v9060141
Received: 20 April 2017 / Revised: 23 May 2017 / Accepted: 2 June 2017 / Published: 8 June 2017
Cited by 41 | Viewed by 4130 | PDF Full-text (2138 KB) | HTML Full-text | XML Full-text
Abstract
In this review, we assess our current understanding of the role of bacteriophages infecting the human gut bacterial community in health and disease. In general, bacteriophages contribute to the structure of their microbial communities by driving host and viral diversification, bacterial evolution, and [...] Read more.
In this review, we assess our current understanding of the role of bacteriophages infecting the human gut bacterial community in health and disease. In general, bacteriophages contribute to the structure of their microbial communities by driving host and viral diversification, bacterial evolution, and by expanding the functional diversity of ecosystems. Gut bacteriophages are an ensemble of unique and shared phages in individuals, which encompass temperate phages found predominately as prophage in gut bacteria (prophage reservoir) and lytic phages. In healthy individuals, only a small fraction of the prophage reservoir is activated and found as extracellular phages. Phage community dysbiosis is characterized by a shift in the activated prophage community or an increase of lytic phages, and has been correlated with disease, suggesting that a proper balance between lysis and lysogeny is needed to maintain health. Consequently, the concept of microbial dysbiosis might be extended to the phage component of the microbiome as well. Understanding the dynamics and mechanisms to restore balance after dysbiosis is an active area of research. The use of phage transplants to re-establish health suggests that phages can be used as disease treatment. Such advances represent milestones in our understanding of gut phages in human health and should fuel research on their role in health and disease. Full article
(This article belongs to the Special Issue Viruses of Microbes)
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Open AccessArticle
Serotype-Specific Killing of Large Cell Carcinoma Cells by Reovirus
Viruses 2017, 9(6), 140; https://doi.org/10.3390/v9060140
Received: 1 May 2017 / Revised: 30 May 2017 / Accepted: 1 June 2017 / Published: 6 June 2017
Cited by 4 | Viewed by 1662 | PDF Full-text (3518 KB) | HTML Full-text | XML Full-text
Abstract
Reovirus is under development as a therapeutic for numerous types of cancer. In contrast to other oncolytic viruses, the safety and efficacy of reovirus have not been improved through genetic manipulation. Here, we tested the oncolytic capacity of recombinant strains (rs) of prototype [...] Read more.
Reovirus is under development as a therapeutic for numerous types of cancer. In contrast to other oncolytic viruses, the safety and efficacy of reovirus have not been improved through genetic manipulation. Here, we tested the oncolytic capacity of recombinant strains (rs) of prototype reovirus laboratory strains T1L and T3D (rsT1L and rsT3D, respectively) in a panel of non-small cell lung cancer (NSCLC) cell lines. We found that rsT1L was markedly more cytolytic than rsT3D in the large cell carcinoma cell lines tested, whereas killing of adenocarcinoma cell lines was comparable between rsT1L and rsT3D. Importantly, non-recombinant T1L and T3D phenocopied the kinetics and magnitude of cell death induced by recombinant strains. We identified gene segments L2, L3, and M1 as viral determinants of strain-specific differences cell killing of the large cell carcinoma cell lines. Together, these results indicate that recombinant reoviruses recapitulate the cell killing properties of non-recombinant, tissue culture-passaged strains. These studies provide a baseline for the use of reverse genetics with the specific objective of engineering more effective reovirus oncolytics. This work raises the possibility that type 1 reoviruses may have the capacity to serve as more effective oncolytics than type 3 reoviruses in some tumor types. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessReview
Detection of HBV Covalently Closed Circular DNA
Viruses 2017, 9(6), 139; https://doi.org/10.3390/v9060139
Received: 4 April 2017 / Revised: 30 May 2017 / Accepted: 30 May 2017 / Published: 6 June 2017
Cited by 11 | Viewed by 2427 | PDF Full-text (6050 KB) | HTML Full-text | XML Full-text
Abstract
Chronic hepatitis B virus (HBV) infection affects approximately 240 million people worldwide and remains a serious public health concern because its complete cure is impossible with current treatments. Covalently closed circular DNA (cccDNA) in the nucleus of infected cells cannot be eliminated by [...] Read more.
Chronic hepatitis B virus (HBV) infection affects approximately 240 million people worldwide and remains a serious public health concern because its complete cure is impossible with current treatments. Covalently closed circular DNA (cccDNA) in the nucleus of infected cells cannot be eliminated by present therapeutics and may result in persistence and relapse. Drug development targeting cccDNA formation and maintenance is hindered by the lack of efficient cccDNA models and reliable cccDNA detection methods. Southern blotting is regarded as the gold standard for quantitative cccDNA detection, but it is complicated and not suitable for high-throughput drug screening, so more sensitive and simple methods, including polymerase chain reaction (PCR)-based methods, Invader assays, in situ hybridization and surrogates, have been developed for cccDNA detection. However, most methods are not reliable enough, and there are no unified standards for these approaches. This review will summarize available methods for cccDNA detection. It is hoped that more robust methods for cccDNA monitoring will be developed and that standard operation procedures for routine cccDNA detection in scientific research and clinical monitoring will be established. Full article
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Open AccessReview
Viral Encephalitis of Unknown Cause: Current Perspective and Recent Advances
Viruses 2017, 9(6), 138; https://doi.org/10.3390/v9060138
Received: 17 May 2017 / Revised: 30 May 2017 / Accepted: 31 May 2017 / Published: 6 June 2017
Cited by 13 | Viewed by 2593 | PDF Full-text (678 KB) | HTML Full-text | XML Full-text
Abstract
Viral encephalitis causes acute inflammation of the brain parenchyma and is a significant cause of human morbidity and mortality. Although Herpes Simplex encephalitis is the most frequent known cause of fatal sporadic encephalitis in humans, an increasingly wide range of viruses and other [...] Read more.
Viral encephalitis causes acute inflammation of the brain parenchyma and is a significant cause of human morbidity and mortality. Although Herpes Simplex encephalitis is the most frequent known cause of fatal sporadic encephalitis in humans, an increasingly wide range of viruses and other microbial pathogens are implicated. Up to 60% of cases of presumed viral encephalitis remain unexplained due to the failure of conventional laboratory techniques to detect an infectious agent. High-throughput DNA sequencing technologies have the potential to detect any microbial nucleic acid present in a biological specimen without any prior knowledge of the target sequence. While there remain challenges intrinsic to these technologies, they have great promise in virus discovery in unexplained encephalitis. Full article
(This article belongs to the Special Issue Astroviruses)
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Open AccessReview
The 5′ and 3′ Untranslated Regions of the Flaviviral Genome
Viruses 2017, 9(6), 137; https://doi.org/10.3390/v9060137
Received: 5 April 2017 / Revised: 16 May 2017 / Accepted: 29 May 2017 / Published: 6 June 2017
Cited by 28 | Viewed by 2453 | PDF Full-text (684 KB) | HTML Full-text | XML Full-text
Abstract
Flaviviruses are enveloped arthropod-borne viruses with a single-stranded, positive-sense RNA genome that can cause serious illness in humans and animals. The 11 kb 5′ capped RNA genome consists of a single open reading frame (ORF), and is flanked by 5′ and 3′ untranslated [...] Read more.
Flaviviruses are enveloped arthropod-borne viruses with a single-stranded, positive-sense RNA genome that can cause serious illness in humans and animals. The 11 kb 5′ capped RNA genome consists of a single open reading frame (ORF), and is flanked by 5′ and 3′ untranslated regions (UTR). The ORF is a polyprotein that is processed into three structural and seven non-structural proteins. The UTRs have been shown to be important for viral replication and immune modulation. Both of these regions consist of elements that are essential for genome cyclization, resulting in initiation of RNA synthesis. Genome mutation studies have been employed to investigate each component of the essential elements to show the necessity of each component and its role in viral RNA replication and growth. Furthermore, the highly structured 3′UTR is responsible for the generation of subgenomic flavivirus RNA (sfRNA) that helps the virus evade host immune response, thereby affecting viral pathogenesis. In addition, changes within the 3′UTR have been shown to affect transmissibility between vector and host, which can influence the development of vaccines. Full article
(This article belongs to the Special Issue Recent Progress in Dengue Virus Research 2016)
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Open AccessArticle
Two Synechococcus genes, Two Different Effects on Cyanophage Infection
Viruses 2017, 9(6), 136; https://doi.org/10.3390/v9060136
Received: 7 April 2017 / Revised: 22 May 2017 / Accepted: 23 May 2017 / Published: 2 June 2017
Cited by 3 | Viewed by 1626 | PDF Full-text (1448 KB) | HTML Full-text | XML Full-text
Abstract
Synechococcus is an abundant marine cyanobacterium that significantly contributes to primary production. Lytic phages are thought to have a major impact on cyanobacterial population dynamics and evolution. Previously, an investigation of the transcriptional response of three Synechococcus strains to infection by the T4-like [...] Read more.
Synechococcus is an abundant marine cyanobacterium that significantly contributes to primary production. Lytic phages are thought to have a major impact on cyanobacterial population dynamics and evolution. Previously, an investigation of the transcriptional response of three Synechococcus strains to infection by the T4-like cyanomyovirus, Syn9, revealed that while the transcript levels of the vast majority of host genes declined soon after infection, those for some genes increased or remained stable. In order to assess the role of two such host-response genes during infection, we inactivated them in Synechococcus sp. strain WH8102. One gene, SYNW1659, encodes a domain of unknown function (DUF3387) that is associated with restriction enzymes. The second gene, SYNW1946, encodes a PIN-PhoH protein, of which the PIN domain is common in bacterial toxin-antitoxin systems. Neither of the inactivation mutations impacted host growth or the length of the Syn9 lytic cycle. However, the DUF3387 mutant supported significantly lower phage DNA replication and yield of phage progeny than the wild-type, suggesting that the product of this host gene aids phage production. The PIN-PhoH mutant, on the other hand, allowed for significantly higher Syn9 genomic DNA replication and progeny production, suggesting that this host gene plays a role in restraining the infection process. Our findings indicate that host-response genes play a functional role during infection and suggest that some function in an attempt at defense against the phage, while others are exploited by the phage for improved infection. Full article
(This article belongs to the Special Issue Marine Viruses 2016) Printed Edition available
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Open AccessArticle
Immunologic and Virologic Mechanisms for Partial Protection from Intravenous Challenge by an Integration-Defective SIV Vaccine
Viruses 2017, 9(6), 135; https://doi.org/10.3390/v9060135
Received: 20 April 2017 / Revised: 20 May 2017 / Accepted: 29 May 2017 / Published: 2 June 2017
Cited by 2 | Viewed by 1607 | PDF Full-text (4922 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The suppression of viral loads and identification of selection signatures in non-human primates after challenge are indicators for effective human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccines. To mimic the protective immunity elicited by attenuated SIV vaccines, we developed an integration-defective SIV (idSIV) [...] Read more.
The suppression of viral loads and identification of selection signatures in non-human primates after challenge are indicators for effective human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccines. To mimic the protective immunity elicited by attenuated SIV vaccines, we developed an integration-defective SIV (idSIV) vaccine by inactivating integrase, mutating sequence motifs critical for integration, and inserting the cytomegalovirus (CMV) promoter for more efficient expression in the SIVmac239 genome. Chinese rhesus macaques were immunized with idSIV DNA and idSIV particles, and the cellular and humoral immune responses were measured. After the intravenous SIVmac239 challenge, viral loads were monitored and selection signatures in viral genomes from vaccinated monkeys were identified by single genome sequencing. T cell responses, heterologous neutralization against tier-1 viruses, and antibody-dependent cellular cytotoxicity (ADCC) were detected in idSIV-vaccinated macaques post immunization. After challenge, the median peak viral load in the vaccine group was significantly lower than that in the control group. However, this initial viral control did not last as viral set-points were similar between vaccinated and control animals. Selection signatures were identified in Nef, Gag, and Env proteins in vaccinated and control macaques, but these signatures were different, suggesting selection pressure on viruses from vaccine-induced immunity in the vaccinated animals. Our results showed that the idSIV vaccine exerted some pressure on the virus population early during the infection but future modifications are needed in order to induce more potent immune responses. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessArticle
Characterization and Temperature Dependence of Arctic Micromonas polaris Viruses
Viruses 2017, 9(6), 134; https://doi.org/10.3390/v9060134
Received: 4 March 2017 / Revised: 24 May 2017 / Accepted: 25 May 2017 / Published: 2 June 2017
Cited by 9 | Viewed by 3426 | PDF Full-text (4236 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Global climate change-induced warming of the Artic seas is predicted to shift the phytoplankton community towards dominance of smaller-sized species due to global warming. Yet, little is known about their viral mortality agents despite the ecological importance of viruses regulating phytoplankton host dynamics [...] Read more.
Global climate change-induced warming of the Artic seas is predicted to shift the phytoplankton community towards dominance of smaller-sized species due to global warming. Yet, little is known about their viral mortality agents despite the ecological importance of viruses regulating phytoplankton host dynamics and diversity. Here we report the isolation and basic characterization of four prasinoviruses infectious to the common Arctic picophytoplankter Micromonas. We furthermore assessed how temperature influenced viral infectivity and production. Phylogenetic analysis indicated that the putative double-stranded DNA (dsDNA) Micromonas polaris viruses (MpoVs) are prasinoviruses (Phycodnaviridae) of approximately 120 nm in particle size. One MpoV showed intrinsic differences to the other three viruses, i.e., larger genome size (205 ± 2 vs. 191 ± 3 Kb), broader host range, and longer latent period (39 vs. 18 h). Temperature increase shortened the latent periods (up to 50%), increased the burst size (up to 40%), and affected viral infectivity. However, the variability in response to temperature was high for the different viruses and host strains assessed, likely affecting the Arctic picoeukaryote community structure both in the short term (seasonal cycles) and long term (global warming). Full article
(This article belongs to the Special Issue Marine Viruses 2016) Printed Edition available
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Open AccessArticle
Redistribution of Endosomal Membranes to the African Swine Fever Virus Replication Site
Viruses 2017, 9(6), 133; https://doi.org/10.3390/v9060133
Received: 4 April 2017 / Revised: 19 May 2017 / Accepted: 25 May 2017 / Published: 1 June 2017
Cited by 1 | Viewed by 1689 | PDF Full-text (10274 KB) | HTML Full-text | XML Full-text
Abstract
African swine fever virus (ASFV) infection causes endosomal reorganization. Here, we show that the virus causes endosomal congregation close to the nucleus as the infection progresses, which is necessary to build a compact viral replication organelle. ASFV enters the cell by the endosomal [...] Read more.
African swine fever virus (ASFV) infection causes endosomal reorganization. Here, we show that the virus causes endosomal congregation close to the nucleus as the infection progresses, which is necessary to build a compact viral replication organelle. ASFV enters the cell by the endosomal pathway and reaches multivesicular late endosomes. Upon uncoating and fusion, the virus should exit to the cytosol to start replication. ASFV remodels endosomal traffic and redistributes endosomal membranes to the viral replication site. Virus replication also depends on endosomal membrane phosphoinositides (PtdIns) synthesized by PIKfyve. Endosomes could act as platforms providing membranes and PtdIns, necessary for ASFV replication. Our study has revealed that ASFV reorganizes endosome dynamics, in order to ensure a productive infection. Full article
(This article belongs to the Special Issue Porcine Viruses) Printed Edition available
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Open AccessArticle
Real-Time Expression Analysis of Selected Anticarsia gemmatalis multiple nucleopolyhedrovirus Gene Promoters during Infection of Permissive, Semipermissive and Nonpermissive Cell Lines
Viruses 2017, 9(6), 132; https://doi.org/10.3390/v9060132
Received: 26 March 2017 / Revised: 22 May 2017 / Accepted: 24 May 2017 / Published: 1 June 2017
Cited by 1 | Viewed by 2066 | PDF Full-text (3335 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Baculovirus infection follows a transcriptionally controlled sequence of gene expression that occurs by activation of different viral gene promoter sequences during infection. This sequence of promoter activation may be disrupted by cellular defenses against viral infection, which might interfere with viral progeny formation. [...] Read more.
Baculovirus infection follows a transcriptionally controlled sequence of gene expression that occurs by activation of different viral gene promoter sequences during infection. This sequence of promoter activation may be disrupted by cellular defenses against viral infection, which might interfere with viral progeny formation. In this work, the activity of the ie1, gp64, lef-1, vp39, p6.9 and polh promoters of the Anticarsia gemmatalis multiple nucleopolyhedrovirus was assessed during infection of permissive, semipermissive and nonpermissive cell lines by a novel methodology that detects reporter protein luminescence in real-time. This technique allowed us to characterize in rich detail the AgMNPV promoters in permissive cell lines and revealed differential profiles of expression in cells with limited permissivity that correlate well with limitations in viral DNA replication. Semipermissive and nonpermissive cell lines presented delays and restrictions in late and very late promoter expression. Cells undergoing apoptosis did not inhibit late gene expression; however, viral progeny formation is severely affected. This work demonstrates the application of the real-time luminescence detection methodology and how the promoter expression profile may be used to diagnose cellular permissivity to baculovirus infection. Full article
(This article belongs to the Section Insect Viruses)
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Open AccessReview
The Role of Somatic L1 Retrotransposition in Human Cancers
Viruses 2017, 9(6), 131; https://doi.org/10.3390/v9060131
Received: 17 March 2017 / Revised: 9 May 2017 / Accepted: 22 May 2017 / Published: 31 May 2017
Cited by 16 | Viewed by 2729 | PDF Full-text (378 KB) | HTML Full-text | XML Full-text
Abstract
The human LINE-1 (or L1) element is a non-LTR retrotransposon that is mobilized through an RNA intermediate by an L1-encoded reverse transcriptase and other L1-encoded proteins. L1 elements remain actively mobile today and continue to mutagenize human genomes. Importantly, when new insertions disrupt [...] Read more.
The human LINE-1 (or L1) element is a non-LTR retrotransposon that is mobilized through an RNA intermediate by an L1-encoded reverse transcriptase and other L1-encoded proteins. L1 elements remain actively mobile today and continue to mutagenize human genomes. Importantly, when new insertions disrupt gene function, they can cause diseases. Historically, L1s were thought to be active in the germline but silenced in adult somatic tissues. However, recent studies now show that L1 is active in at least some somatic tissues, including epithelial cancers. In this review, we provide an overview of these recent developments, and examine evidence that somatic L1 retrotransposition can initiate and drive tumorigenesis in humans. Recent studies have: (i) cataloged somatic L1 activity in many epithelial tumor types; (ii) identified specific full-length L1 source elements that give rise to somatic L1 insertions; and (iii) determined that L1 promoter hypomethylation likely plays an early role in the derepression of L1s in somatic tissues. A central challenge moving forward is to determine the extent to which L1 driver mutations can promote tumor initiation, evolution, and metastasis in humans. Full article
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Open AccessReview
Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation of Long-Terminal Repeats (LTRs)
Viruses 2017, 9(6), 130; https://doi.org/10.3390/v9060130
Received: 10 March 2017 / Revised: 22 May 2017 / Accepted: 22 May 2017 / Published: 31 May 2017
Cited by 16 | Viewed by 1984 | PDF Full-text (241 KB) | HTML Full-text | XML Full-text
Abstract
Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human genome. This could represent a significant pathogenic burden but it is becoming more evident that many of these elements have a positive contribution to make to normal human physiology. In particular, [...] Read more.
Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human genome. This could represent a significant pathogenic burden but it is becoming more evident that many of these elements have a positive contribution to make to normal human physiology. In particular, the contributions of human ERVs (HERVs) to gene regulation and the expression of noncoding RNAs has been revealed with the help of new and emerging genomic technologies. HERVs have the common provirus structure of coding open reading frames (ORFs) flanked by two long-terminal repeats (LTRs). However, over the course of evolution and as a consequence of host defence mechanisms, most of the sequences contain INDELs, mutations or have been reduced to single LTRs by recombination. These INDELs and mutations reduce HERV activity. However, there is a trade-off for the host cells in that HERVs can provide beneficial sources of genetic variation but with this benefit comes the risk of pathogenic activity and spread within the genome. For example, the LTRs are of critical importance as they contain promoter sequences and can regulate not only HERV expression but that of human genes. This is true even when the LTRs are located in intergenic regions or are in antisense orientation to the rest of the gene. Uncontrolled, this promoter activity could disrupt normal gene expression or transcript processing (e.g., splicing). Thus, control of HERVs and particularly their LTRs is essential for the cell to manage these elements and this control is achieved at multiple levels, including epigenetic regulations that permit HERV expression in the germline but silence it in most somatic tissues. We will discuss some of the common epigenetic mechanisms and how they affect HERV expression, providing detailed discussions of HERVs in stem cell, placenta and cancer biology. Full article
Open AccessReview
The Role of Caveolin 1 in HIV Infection and Pathogenesis
Viruses 2017, 9(6), 129; https://doi.org/10.3390/v9060129
Received: 23 March 2017 / Revised: 2 May 2017 / Accepted: 22 May 2017 / Published: 26 May 2017
Cited by 2 | Viewed by 2584 | PDF Full-text (1087 KB) | HTML Full-text | XML Full-text
Abstract
Caveolin 1 (Cav-1) is a major component of the caveolae structure and is expressed in a variety of cell types including macrophages, which are susceptible to human immunodeficiency virus (HIV) infection. Caveolae structures are present in abundance in mechanically stressed cells such as [...] Read more.
Caveolin 1 (Cav-1) is a major component of the caveolae structure and is expressed in a variety of cell types including macrophages, which are susceptible to human immunodeficiency virus (HIV) infection. Caveolae structures are present in abundance in mechanically stressed cells such as endothelial cells and adipocytes. HIV infection induces dysfunction of these cells and promotes pathogenesis. Cav-1 and the caveolae structure are believed to be involved in multiple cellular processes that include signal transduction, lipid regulation, endocytosis, transcytosis, and mechanoprotection. Such a broad biological role of Cav-1/caveolae is bound to have functional cross relationships with several molecular pathways including HIV replication and viral-induced pathogenesis. The current review covers the relationship of Cav-1 and HIV in respect to viral replication, persistence, and the potential role in pathogenesis. Full article
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