Abstract
Alphaviruses such as chikungunya virus (CHIKV) and Semliki Forest virus (SFV) are small enveloped RNA viruses that bud from the plasma membrane. Tetherin/BST2 is an interferon-induced host membrane protein that inhibits the release of many enveloped viruses via direct tethering of budded particles to the cell surface. Alphaviruses have highly organized structures and exclude host membrane proteins from the site of budding, suggesting that their release might be insensitive to tetherin inhibition. Here, we demonstrated that exogenously-expressed tetherin efficiently inhibited the release of SFV and CHIKV particles from host cells without affecting virus entry and infection. Alphavirus release was also inhibited by the endogenous levels of tetherin in HeLa cells. While rubella virus (RuV) and dengue virus (DENV) have structural similarities to alphaviruses, tetherin inhibited the release of RuV but not DENV. We found that two recently identified tetherin isoforms differing in length at the N-terminus exhibited distinct capabilities in restricting alphavirus release. SFV exit was efficiently inhibited by the long isoform but not the short isoform of tetherin, while both isoforms inhibited vesicular stomatitis virus exit. Thus, in spite of the organized structure of the virus particle, tetherin specifically blocks alphavirus release and shows an interesting isoform requirement.
Highlights
Alphaviruses are small enveloped plus-sense RNA viruses that include important human pathogens such as chikungunya virus (CHIKV) and Venezuelan equine encephalitis virus (VEEV) [1]
A report by Atasheva et al showed that VEEV infection induces the expression of a number of interferon-stimulated genes including tetherin, and that the overall growth of VEEV is inhibited by expression of murine tetherin [53]
Human tetherin causes an accumulation of CHIKV virus-like particles (VLP) on the plasma membrane as observed by scanning electron microscopy [54], and decreases production of infectious CHIKV [55]
Summary
Alphaviruses are small enveloped plus-sense RNA viruses that include important human pathogens such as chikungunya virus (CHIKV) and Venezuelan equine encephalitis virus (VEEV) [1]. The alphavirus genus is in the Togaviridae family, which includes the rubivirus rubella virus (RuV). Alphaviruses such as CHIKV and the encephalitic alphaviruses are listed as priority pathogens by the Centers for Disease Control because of their emerging nature, serious effects on human health, and potential to be exploited as biological weapons. The nucleocapsid contains one copy of the genomic RNA enclosed in a shell formed by 240 copies of the capsid protein This core is enveloped by a lipid bilayer studded with 240 copies of the viral envelope glycoproteins E2, which mediates receptor binding, and E1, the membrane fusion protein [6,7].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
