Abstract
BackgroundHSV-2 is the major cause of genital herpes. We previously demonstrated that the host viral restriction factor tetherin restricts HSV-2 release and is antagonized by several HSV-2 glycoproteins. However, the mechanisms underlying HSV-2 glycoproteins mediated counteraction of tetherin remain unclear. In this study, we investigated whether tetherin restricts the cell-to-cell spread of HSV-2 and the mechanisms underlying HSV-2 gD mediated antagonism of tetherin.MethodsInfectious center assays were used to test whether tetherin could affect cell-to-cell spread of HSV-2. Coimmunoprecipitation assays were performed to map the tetherin domains required for HSV-2 gD-mediated downregulation. Immunoflurence assays were performed to detect the accumulation of tetherin in lysosomes or proteasomes. All experiments were repeated for at least three times and the data were performed statistical analysis.Results1) Tetherin restricts cell-to-cell spread of HSV-2; 2) HSV-2 gD specifically interacts with the CC domain of tetherin; 3) HSV-2 gD promotes tetherin to the lysosomal degradation pathway.ConclusionsTetherin not only restricts HSV-2 release but also its cell-to-cell spread. In turn, HSV-2 gD targets the CC domain of tetherin and promotes its degradation in the lysosome. Findings in this study have increased our understanding of tetherin restriction and viral countermeasures.
Highlights
Herpes simplex virus (HSV)-2 is the major cause of genital herpes
We investigated whether tetherin restricts the cell-to-cell spread of Herpes simplex virus 2 (HSV-2) and the mechanisms underlying HSV-2 glycoprotein D (gD) mediated antagonism of tetherin
Tetherin restricts cell-to-cell spread of HSV-2 Spread of HSV-2 progeny virus can occur both by release of mature infectious virus particles into the extracellular medium and by viral cell-to-cell spread
Summary
HSV-2 is the major cause of genital herpes. We previously demonstrated that the host viral restriction factor tetherin restricts HSV-2 release and is antagonized by several HSV-2 glycoproteins. The mechanisms underlying HSV-2 glycoproteins mediated counteraction of tetherin remain unclear. We investigated whether tetherin restricts the cell-to-cell spread of HSV-2 and the mechanisms underlying HSV-2 gD mediated antagonism of tetherin. The mechanisms underlying HIV-1 counteracts tetherin have been intensively investigated, but less attention has been paid to understanding those mediated by other viruses. The HSV-2 glycoprotein D (gD), a major component of the virion envelope, was previously revealed to be essential for viral fusion and plays an important role in the cell-to-cell spread of the virus in permissive cells [30, 31]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have