Modulation of hepatitis C virus release by the interferon-induced protein BST-2/tetherin

Huang

Journal of Medical Virology

2019

BST2/tetherin, an interferon‐inducible antiviral factor, can block the cellular release of various enveloped viruses. We previously reported that human coronavirus 229E (HCoV‐229E) infection can alleviate the BST2 tethering of HIV‐1 virions by downregulating cell surface BST2, suggesting that coronaviruses are capable of encoding anti‐BST2 factors. Here we report our new finding that severe acute respiratory syndrome coronavirus (SARS‐CoV) spike (S) glycoprotein, similar to Vpu, is capable of antagonizing the BST2 tethering of SARS‐CoV, HCoV‐229E, and HIV‐1 virus‐like particles via BST2 downregulation. However, unlike Vpu (which downmodulates BST2 by means of proteasomal and lysosomal degradation pathways), BST2 downregulation is apparently mediated by SARS‐CoV S through the lysosomal degradation pathway only. We found that SARS‐CoV S colocalized with both BST2 and reduced cell surface BST2, suggesting an association between SARS‐CoV S and BST2 that targets the lysosomal degradation pathway. According to one recent report, SARS‐CoV ORF7a antagonizes BST2 by interfering with BST2 glycosylation1. Our data provide support for the proposal that SARS‐CoV and other enveloped viruses are capable of evolving supplementary anti‐BST2 factors in a manner that requires virus replication. Further experiments are required to determine whether the BST2‐mediated restriction of authentic SARS‐CoV virions is alleviated by the SARS‐CoV spike protein.

Section: Introductionmentioning

confidence: 56%

Severe acute respiratory syndrome coronavirus spike protein counteracts BST2‐mediated restriction of virus‐like particle release

Huang

Journal of Medical Virology

2019

“…However, some enveloped viruses such as herpesviruses (which complete their final envelopment by obtaining membranes from TGN and/or endosomal compartments and egress via exocytosis), are also subject to BST2 restrictions Mansouri et al, 2009;Mettenleiter, 2002). Results from one recent study suggest that BST2 can moderately restrict the release of hepatitis C virus (HCV), whose assembly takes place in the ER, and whose release from cells occurs via secretory pathways in a fashion similar to that of coronaviruses (Dafa-Berger et al, 2012;Jones and McLauchlan, 2010). It is possible that virions linked to vesicle membranes via BST2 association are retained on cell surfaces following the exocytotic fusion of virion-containing vesicles with plasma membranes.…”

Section: Discussionmentioning

confidence: 99%

BST2/CD317 counteracts human coronavirus 229E productive infection by tethering virions at the cell surface

2014

Bone marrow stromal antigen 2 (BST2), an interferon-inducible antiviral factor, has been shown to block the release of various enveloped viruses from cells. It has also been identified as an innate immune system component. Most enveloped viruses subject to BST2 restriction bud at the plasma membrane. Here we report our findings that (a) the production of human coronavirus 229E (HCoV-229E) progeny viruses, whose budding occurs at the ER-Golgi intermediate compartment (ERGIC), markedly decreases in the presence of BST2; and (b) BST2 knockdown expression results in enhanced HCoV-229E virion production. Electron microscopy analyses indicate that HCoV-229E virions are tethered to cell surfaces or intracellular membranes by BST2. Our results suggest that BST2 exerts a broad blocking effect against enveloped virus release, regardless of whether budding occurs at the plasma membrane or intracellular compartments.

“…IFN induces the expression of lncRNA BST2 or BISPR in several cell lines (Kambara et al, 2015; Barriocanal et al, 2015). BISPR is located head-to-head with BST2/tetherin, a well-characterized antiviral factor that attaches viruses to the cell surface and impedes viral release (Dafa-Berger et al, 2012; Neil et al, 2008). Both BISPR and BST2 are corregulated and it has been shown that BISPR acts in trans to induce transcription of BST2 gene, probably, by counteracting the repressive action of PRC2 (Kambara et al, 2015; Barriocanal et al, 2015).…”

Section: Viruses and Lncrnasmentioning

confidence: 99%

Long noncoding RNAs in viral infections

2016

Viral infections induce strong modifications in the cell transcriptome. Among the RNAs whose expression is altered by infection are long noncoding RNAs (lncRNAs). LncRNAs are transcripts with potential to function as RNA molecules. Infected cells may express viral lncRNAs, cellular lncRNAs and chimeric lncRNAs formed by viral and cellular sequences. Some viruses express viral lncRNAs whose function is essential for viral viability. They are transcribed by polymerase II or III and some of them can be processed by unique maturation steps performed by host cell machineries. Some viral lncRNAs control transcription, stability or translation of cellular and viral genes. Surprisingly, similar functions can be exerted by cellular lncRNAs induced by infection. Expression of cellular lncRNAs may be altered in response to viral replication or viral protein expression. However, many cellular lncRNAs respond to the antiviral pathways induced by infection. In fact, many lncRNAs function as positive or negative regulators of the innate antiviral response. Our current knowledge about the identity and function of lncRNAs in infected cells is very limited. However, research into this field has already helped in the identification of novel cellular pathways and may help in the development of therapeutic tools for the treatment of viral infections, autoimmune diseases, neurological disorders and cancer.