The Journal of general virology最新文献

Members of the family Pleolipoviridae are pseudo-spherical and pleomorphic archaeal viruses composed of a membrane vesicle, which encloses a DNA genome. The genome is either circular ssDNA or dsDNA, or linear dsDNA molecules of approximately 7 to 17 kilonucleotides or kbp. Typically, virions contain a single type of transmembrane spike protein at the envelope and a single type of membrane protein, which is embedded in the envelope and located in the internal side of the membrane. All viruses infect extremely halophilic archaea in the class Halobacteria (phylum Euryarchaeota). Pleolipoviruses have a narrow host range and a persistent, non-lytic life cycle. Some viruses are temperate and can integrate into the host chromosome. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Pleolipoviridae, which is available at ictv.global/report/pleolipoviridae.

Typical members of the family Mymonaviridae produce filamentous, enveloped virions containing a single molecule of linear, negative-sense RNA of about about 10 kb, but some may not produce any virions. The family includes several genera, some with multiple species. Mymonavirids usually infect filamentous fungi, but a few have been identified associated with insects, oomycetes or plants. At least one virus, Sclerotinia sclerotiorum negative-stranded RNA virus 1, induces hypovirulence in its fungal host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Mymonaviridae, which is available at ictv.global/report/mymonaviridae.

Ferrets are widely used for experimental modelling of viral infections. However, background disease in ferrets could potentially confound intended experimental interpretation. Here we report the detection of a subclinical infection of ferret hepatitis E virus (FRHEV) within a colony sub-group of female laboratory ferrets that had been enrolled on an experimental viral infection study (non-hepatitis). Lymphoplasmacytic cuffing of periportal spaces was identified on histopathology but was negative for the RNA and antigens of the administered virus. Follow-up viral metagenomic analysis conducted on liver specimens revealed sequences attributed to FRHEV and these were confirmed by reverse-transcriptase polymerase chain reaction. Further genomic analysis revealed contiguous sequences spanning 79-95 % of the FRHEV genome and that the sequences were closely related to those reported previously in Europe. Using in situ hybridization by RNAScope, we confirmed the presence of HEV-specific RNA in hepatocytes. The HEV open reading frame 2 (ORF2) protein was also detected by immunohistochemistry in the hepatocytes and the biliary canaliculi. In conclusion, the results of our study provide evidence of background infection with FRHEV in laboratory ferrets. As this infection can be subclinical, we recommend routine monitoring of ferret populations using virological and liver function tests to avoid incorrect causal attribution of any liver disease detected in in vivo studies.

Antiviral therapy for human cytomegalovirus (HCMV) currently relies upon direct-acting antiviral drugs. However, it is now well known that these drugs have shortcomings, which limit their use. Here I review the identification and investigation of compounds targeting cellular proteins that have anti-HCMV activity and could supersede those anti-HCMV drugs currently in use. This includes discussion of drug repurposing, for example the use of artemisinin compounds, and discussion of new directions to identify compounds that target cellular factors in HCMV-infected cells, for example screening of kinase inhibitors. In addition, I highlight developing areas such as the use of machine learning and emphasize how interaction with fields outside virology will be critical for development of anti-HCMV compounds.

Bracoviruses and ichnoviruses are endogenous viruses of parasitic wasps that produce particles containing virulence genes expressed in host tissues and necessary for parasitism success. In the case of bracoviruses the particles are produced by conserved genes of nudiviral origin integrated permanently in the wasp genome, whereas the virulence genes can strikingly differ depending on the wasp lineage. To date most data obtained on bracoviruses concerned species from the braconid subfamily of Microgastrinae. To gain a broader view on the diversity of virulence genes we sequenced the genome packaged in the particles of Chelonus inanitus bracovirus (CiBV) produced by a wasp belonging to a different subfamily: the Cheloninae. These are egg-larval parasitoids, which means that they oviposit into the host egg and the wasp larvae then develop within the larval stages of the host. We found that most of CiBV virulence genes belong to families that are specific to Cheloninae. As other bracoviruses and ichnoviruses however, CiBV encode v-ank genes encoding truncated versions of the immune cactus/IκB factor, which suggests these proteins might play a key role in host-parasite interactions involving domesticated endogenous viruses. We found that the structures of CiBV V-ANKs are different from those previously reported. Phylogenetic analysis supports the hypothesis that they may originate from a cactus/IκB immune gene from the wasp genome acquired by the bracovirus. However, their evolutionary history is different from that shared by other V-ANKs, whose common origin probably reflects horizontal gene transfer events of virus sequences between braconid and ichneumonid wasps.

In Africa, several emerging zoonotic viruses have been transmitted from small mammals such as rodents and shrews to humans. Although no clinical cases of small mammal-borne viral diseases have been reported in Central Africa, potential zoonotic viruses have been identified in rodents in the region. Therefore, we hypothesized that there may be unrecognized zoonotic viruses circulating in small mammals in Central Africa. Here, we investigated viruses that have been maintained among wild small mammals in Gabon to understand their potential risks to humans. We identified novel orthonairoviruses in 24.6 % of captured rodents and shrews from their kidney total RNA samples. Phylogenetic analysis revealed that the novel viruses, Lamusara virus (LMSV) and Lamgora virus, were closely related to Erve virus, which was previously identified in shrews of the genus Crocidura and has been suspected to cause neuropathogenic diseases in humans. Moreover, we show that the LMSV ovarian tumour domain protease, one of the virulence determination factors of orthonairoviruses, suppressed interferon signalling in human cells, suggesting the possible human pathogenicity of this virus. Taken together, our study demonstrates the presence of novel orthonairoviruses that may pose unrecognized risks of viral disease transmission in Gabon.

Macaque-tropic HIV-1 (HIV-1mt) variants have been developed to establish preferable primate models that are advantageous in understanding HIV-1 infection pathogenesis and in assessing the preclinical efficacy of novel prevention/treatment strategies. We previously reported that a CXCR4-tropic HIV-1mt, MN4Rh-3, efficiently replicates in peripheral blood mononuclear cells (PBMCs) of cynomolgus macaques homozygous for TRIMCyp (CMs^TC). However, the CMs^TC challenged with MN4Rh-3 displayed low viral loads during the acute infection phase and subsequently exhibited short-term viremia. These virological phenotypes in vivo differed from those observed in most HIV-1-infected people. Therefore, further development of the HIV-1mt variant was needed. In this study, we first reconstructed the MN4Rh-3 clone to produce a CCR5-tropic HIV-1mt, AS38. In addition, serial in vivo passages allowed us to produce a highly adapted AS38-derived virus that exhibits high viral loads (up to approximately 10⁶ copies ml^-1) during the acute infection phase and prolonged periods of persistent viremia (lasting approximately 16 weeks postinfection) upon infection of CMs^TC. Whole-genome sequencing of the viral genomes demonstrated that the emergence of a unique 15-nt deletion within the vif gene was associated with in vivo adaptation. The deletion resulted in a significant increase in Vpr protein expression but did not affect Vif-mediated antagonism of antiretroviral APOBEC3s, suggesting that Vpr is important for HIV-1mt adaptation to CMs^TC. In summary, we developed a novel CCR5-tropic HIV-1mt that can induce high peak viral loads and long-term viremia and exhibits increased Vpr expression in CMs^TC.

In this study 163 complete whole-genome sequences of the emerging pathogen grapevine red blotch virus (GRBV; genus Grablovirus, family Geminiviridae) were used to reconstruct phylogenies using Bayesian analyses on time-tipped (heterochronous) data. Using different combinations of priors, Bayes factors identified heterochronous datasets (3×200 million chains) generated from strict clock and exponential tree priors as being the most robust. Substitution rates of 3.2×10^-5 subsitutions per site per year (95% HPD 4.3-2.1×10^-5) across the whole of the GRBV genome were estimated, suggesting ancestral GRBV diverged from ancestral wild Vitis latent virus 1 around 9 000 years ago, well before the first documented arrival of Vitis vinifera in North America. Whole-genome analysis of GRBV isolates in a single infected field-grown grapevine across 12 years identified 12 single nucleotide polymorphisms none of which were fixed substitutions: an observation not discordant with the in silico estimate. The substitution rate estimated here is lower than those estimated for other geminiviruses and is the first for a woody-host-infecting geminivirus.