Human and rodent cell susceptibility and response to different orthohantaviruses uncovers various levels of cellular restriction
Ontology highlight
ABSTRACT:
ORGANISM(S): Myodes glareolus
PROVIDER: GSE198751 | GEO | 2022/09/30
REPOSITORIES: GEO
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Project description:Human and rodent cell susceptibility and response to different orthohantaviruses uncovers various levels of cellular restriction
| PRJNA816819 | ENA
Project description:Orthohantaviruses are rodent-borne emerging viruses known to cause severe diseases in humans but no apparent pathology in their small mammal reservoirs. However, the mechanisms leading to tolerance or pathogenicity in humans and persistence in rodent reservoirs are poorly understood, as is the manner in which they spread within and between organisms. Here, we used a range of cellular and molecular approaches to investigate the interactions of three different orthohantaviruses – Puumala virus (PUUV), responsible for a mild form of hemorrhagic fever in humans, Tula virus (TULV) with low pathogenicity, and nonpathogenic Prospect Hill virus (PHV) – with human and rodent host cell lines. We showed that the three orthohantaviruses were able to infect Vero E6 and HuH7 cells but only the former secreted infectious particles. In cells derived from the PUUV reservoir (Myodes glareolus), PUUV achieved complete viral cycling, while TULV did not enter the cells and PHV infected them but did not produce infectious particles, reflecting some differences in host specificity. A search for mature virions by electron microscopy revealed that TULV assembly occurred in part at the plasma membrane, whereas PHV particles were trapped in autophagic vacuoles in cells of the heterologous rodent host. The interaction of orthohantaviruses with cellular factors was investigated by studying the colocalization of viral nucleocapsids with markers of cell compartments, identifying interactors of viral proteins by mass spectrometry analysis, and measuring the regulation of gene expression by transcriptomic analysis in infected cells. Overall, our study highlighted the complexity of the host-virus relationship, demonstrated that orthohantaviruses were restricted at different levels of the viral cycle, and provided different levels of analysis to further investigate how these viruses differ in their interactions with cells to evade innate immunity and how this depends on the tissue and host species.
2022-10-04 | PXD032365 | Pride
Project description:Host cells infected by various types of viruses
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Project description:Herpesviruses, including the oncogenic Epstein-Barr Virus (EBV), must bypass host DNA sensing mechanisms to drive infection and pathogenesis. The first viral latency protein expressed, EBNA-LP, is essential for the transformation of naïve B cells, yet its role in evading host defenses remains unclear. Using single-cell RNA sequencing of EBNA-LP-Knockout (LPKO)-infected B cells, we reveal an antiviral response landscape implicating the ‘speckled proteins’ as key restriction factors countered by EBNA-LP. Specifically, loss of SP100 or the primate-specific SP140L reverses the restriction of LPKO, suppresses a subset of canonically interferon-stimulated genes, and restores viral gene transcription and cellular proliferation. Notably, we also identify Sp140L as a restriction target of the herpesvirus saimiri ORF3 protein, implying a role in immunity to other DNA viruses. This study reveals Sp140L as a restriction factor that we propose links sensing and transcriptional suppression of viral DNA to an IFN-independent innate immune response, likely relevant to all nuclear DNA viruses.
2024-11-20 | GSE282376 | GEO
Project description:Herpesviruses, including the oncogenic Epstein-Barr Virus (EBV), must bypass host DNA sensing mechanisms to drive infection and pathogenesis. The first viral latency protein expressed, EBNA-LP, is essential for the transformation of naïve B cells, yet its role in evading host defenses remains unclear. Using single-cell RNA sequencing of EBNA-LP-Knockout (LPKO)-infected B cells, we reveal an antiviral response landscape implicating the ‘speckled proteins’ as key restriction factors countered by EBNA-LP. Specifically, loss of SP100 or the primate-specific SP140L reverses the restriction of LPKO, suppresses a subset of canonically interferon-stimulated genes, and restores viral gene transcription and cellular proliferation. Notably, we also identify Sp140L as a restriction target of the herpesvirus saimiri ORF3 protein, implying a role in immunity to other DNA viruses. This study reveals Sp140L as a restriction factor that we propose links sensing and transcriptional suppression of viral DNA to an IFN-independent innate immune response, likely relevant to all nuclear DNA viruses.
2024-11-20 | GSE282377 | GEO
Project description:Acanthamoeba-infecting Mimiviridae belong to three clades: Mimiviruses (A), Moumouviruses (B) and Megaviruses (C). The uniquely complex mobilome of these giant viruses includes virophages and linear 7 kb-DNA molecules called “transpovirons”. We recently isolated a new virophage (Zamilon vitis) and two new transpovirons (maBtv and mvCtv) respectively associated to B-clade and C-clade Mimiviridae. We used the capacity of the Zamilon virophage to replicate both on B-clade and C-clade host viruses to investigate the three partite interaction network governing the propagation of transpovirons. We notably performed proteomic comparisons of host viruses and virophage particles carrying or cleared of transpovirons in search of proteins involved in this adaptation process. These experiments revealed that transpoviron-encoded proteins are synthetized during the combined Mimiviridae/virophage/transpoviron replication process and are specifically incorporated into the virophage and Mimiviridae virions together with the cognate transpoviron DNA. This is a unique example of intricate commensalism in the viral world, where the Zamilon virophage and the transpoviron depend on their host giant virus to replicate, and the transpoviron depends on the virophage to propagate from one host virus to another.
2020-04-14 | PXD009037 | Pride
Project description:Herpesviruses, including the oncogenic Epstein-Barr Virus (EBV), must bypass host DNA sensing mechanisms to drive infection and pathogenesis. The first viral latency protein expressed, EBNA-LP, is essential for the transformation of naïve B cells, yet its role in evading host defenses remains unclear. Using single-cell RNA sequencing of EBNA-LP-Knockout (LPKO)-infected B cells, we reveal an antiviral response landscape implicating the ‘speckled proteins’ as key restriction factors countered by EBNA-LP. Specifically, loss of SP100 or the primate-specific SP140L reverses the restriction of LPKO, suppresses a subset of canonically interferon-stimulated genes, and restores viral gene transcription and cellular proliferation. Notably, we also identify Sp140L as a restriction target of the herpesvirus saimiri ORF3 protein, implying a role in immunity to other DNA viruses. This study reveals Sp140L as a restriction factor that we propose links sensing and transcriptional suppression of viral DNA to an IFN-independent innate immune response, likely relevant to all nuclear DNA viruses.
2024-11-20 | GSE282400 | GEO
Project description:Viruses constantly evolve and adapt to the antiviral defenses of their hosts. The biology of viral circumvention of these selective pressures can often be attributed to the acquisition of novel antagonistic gene products or by rapid genome change that prevents host recognition. To study viral evasion of RNA interference (RNAi)-based defenses, we established a robust antiviral system in mammalian cells using recombinant Sendai virus designed to be targeted by endogenous host microRNAs (miRNAs) with perfect complementarity. Using this system, we previously demonstrated the intrinsic ability of positive-strand RNA viruses to escape this selective pressure via homologous recombination, which was not observed in negative-strand RNA viruses. Here we show that given extensive time, escape of miRNA-targeted Sendai virus was enabled by host adenosine deaminase acting on RNA 1 (ADAR1). Independent of the viral transcript targeted, ADAR1 editing resulted in disruption of the miRNA-silencing motif, suggesting an intolerance for extensive RNA:RNA interactions necessary for antiviral RNAi. This was further supported in N. benthamiana, where exogenous expression of ADAR1 interfered with endogenous RNAi. Together, these results suggest that ADAR1 diminishes the effectiveness of RNAi and may explain why it is absent in species that utilize this antiviral defense system.
2023-03-21 | GSE227592 | GEO
Project description:RNA viruses are a major threat to global human health. The life cycles of many highly pathogenic RNA viruses like influenza A virus (IAV) and Lassa virus depends on host mRNA, as viral polymerases cleave 5′m7G-capped host transcripts to prime viral mRNA synthesis (‘cap-snatching’). We hypothesized that start codons within cap-snatched host transcripts could drive the expression of chimeric human-viral coding sequences. Here, we report the existence of this mechanism of gene origination (‘start-snatching’), which creates, depending on the translatability of the viral UTRs, human-virus protein chimeras either as N-terminally extended viral proteins or entirely novel polypeptides by genetic overprinting. We show that both types of chimeric proteins are made in IAV-infected cells, can generate T cell responses and contribute to virulence. Our results indicate that IAV, and likely a multitude of other human-, animal- and plant-viruses, use this host-dependent mechanism to expand their proteome diversity during infection.
2020-05-15 | GSE148245 | GEO
Project description:The threat of viral pandemics demands a comprehensive understanding of evolution at the host-pathogen interface. Here, we systematically show that the accessibility of adaptive mutations in influenza nucleoprotein at fever-like temperatures is mediated by host chaperones. Particularly noteworthy, we observe that the Pro283 nucleoprotein variant, which is conserved across human flu strains, confers resistance to the MxA antiviral-restriction factor, and critically contributed to the pathogenicity of the 1918 pandemic flu, is rendered unfit by host chaperone depletion. This fitness loss is linked to biophysical defects that chaperones cannot address when heat shock factor-I is inhibited. Thus, host chaperones can be hijacked by viruses to un-couple biophysically deleterious consequences of mutations from the benefits of immune escape. In summary, host chaperones play a central role in shaping influenza adaptation, with implications for the evolution of other viruses, for viral host-switching, and for the design of antiviral strategies refractory to resistance.
2018-09-10 | GSE113649 | GEO