Abstract
Septins are conserved components of the cytoskeleton that play important roles in many fundamental cellular processes including division, migration, and membrane trafficking. Septins can also inhibit bacterial infection by forming cage-like structures around pathogens such as Shigella We found that septins are recruited to vaccinia virus immediately after its fusion with the plasma membrane during viral egress. RNA interference-mediated depletion of septins increases virus release and cell-to-cell spread, as well as actin tail formation. Live cell imaging reveals that septins are displaced from the virus when it induces actin polymerization. Septin loss, however, depends on the recruitment of the SH2/SH3 adaptor Nck, but not the activity of the Arp2/3 complex. Moreover, it is the recruitment of dynamin by the third Nck SH3 domain that displaces septins from the virus in a formin-dependent fashion. Our study demonstrates that septins suppress vaccinia release by "entrapping" the virus at the plasma membrane. This antiviral effect is overcome by dynamin together with formin-mediated actin polymerization.
Highlights
During vaccinia virus infection, the newly assembled intracellular enveloped virus (IEV) is transported on microtubules to the plasma membrane by kinesin-1 (Hollinshead et al, 2001; Rietdorf et al, 2001; Ward and Moss, 2001; Dodding et al, 2011; Leite and Way, 2015; Fig. 1 A)
Septins suppress the release and cell-to-cell spread of vaccinia To understand the role of septins during vaccinia infection, we examined the impact of the loss of SEPT7 on the release and spread of the Western Reserve (WR) strain of vaccinia virus
The increase in plaque size in the absence of SEPT7 is not restricted to WR, as it is apparent in cells infected with WR expressing A36-YdF, a vaccinia strain deficient in actin tail formation and cell-to-cell spread since A36 cannot be phosphorylated on tyrosine 112 or 132 (Rietdorf et al, 2001; Ward and Moss, 2001; Fig. 1 C and Fig. S1 A)
Summary
The newly assembled intracellular enveloped virus (IEV) is transported on microtubules to the plasma membrane by kinesin-1 (Hollinshead et al, 2001; Rietdorf et al, 2001; Ward and Moss, 2001; Dodding et al, 2011; Leite and Way, 2015; Fig. 1 A). Not all virions are immediately released, as some remain attached to the outside of the cell and are referred to as cell-associated enveloped viruses (CEVs; Fig. 1 A; Leite and Way, 2015) These virions are able to signal back into the cell to induce Arp2/3-dependent actin polymerization to enhance their spread into adjacent cells (Cudmore et al, 1995, 1996; Frischknecht et al, 1999; Hollinshead et al, 2001; Ward and Moss, 2001; Doceul et al, 2010). Their transient recruitment helps polarize A36 and N-WASP beneath CEV, leading to more rapid and sustained actin polymerization, which enhances the cell-to-cell spread of vaccinia (Humphries et al, 2012)
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