Abstract
During vaccinia virus morphogenesis, intracellular mature virus (IMV) particles are wrapped by a double lipid bilayer to form triple enveloped virions called intracellular enveloped virus (IEV). IEV are then transported to the cell surface where the outer IEV membrane fuses with the cell membrane to expose a double enveloped virion outside the cell. The F12, E2 and A36 proteins are involved in transport of IEVs to the cell surface. Deletion of the F12L or E2L genes causes a severe inhibition of IEV transport and a tiny plaque size. Deletion of the A36R gene leads to a smaller reduction in plaque size and less severe inhibition of IEV egress. The A36 protein is present in the outer membrane of IEVs, and over-expressed fragments of this protein interact with kinesin light chain (KLC). However, no interaction of F12 or E2 with the kinesin complex has been reported hitherto. Here the F12/E2 complex is shown to associate with kinesin-1 through an interaction of E2 with the C-terminal tail of KLC isoform 2, which varies considerably between different KLC isoforms. siRNA-mediated knockdown of KLC isoform 1 increased IEV transport to the cell surface and virus plaque size, suggesting interaction with KLC isoform 1 is somehow inhibitory of IEV transport. In contrast, knockdown of KLC isoform 2 did not affect IEV egress or plaque formation, indicating redundancy in virion egress pathways. Lastly, the enhancement of plaque size resulting from loss of KLC isoform 1 was abrogated by removal of KLC isoforms 1 and 2 simultaneously. These observations suggest redundancy in the mechanisms used for IEV egress, with involvement of KLC isoforms 1 and 2, and provide evidence of interaction of F12/E2 complex with the kinesin-1 complex.
Highlights
Vaccinia virus (VACV) is a member of the Orthopoxvirus genus of the Poxviridae [1] and is the live vaccine that was used to eradicate smallpox [2]
During transport of new virus particles to the cell surface VACV interacts with a protein
Only the VACV protein A36 has been shown to interact with kinesin-1, viruses lacking A36 still reach the cell surface, albeit at reduced efficiency, indicating other factors are involved
Summary
Vaccinia virus (VACV) is a member of the Orthopoxvirus genus of the Poxviridae [1] and is the live vaccine that was used to eradicate smallpox [2]. Some IMVs are wrapped by membranes derived from the trans-Golgi network or early-endosomes [reviewed in 4] to form the triple enveloped virion called intracellular enveloped virus (IEV) or wrapped virus (WV). IEV particles move to the cell periphery where the outer membrane fuses with the plasma membrane to expose a virion with 2 membranes outside the cell. Some of these virions are retained on the cell surface and are called cell-associated enveloped virus (CEV), and some are released into the extracellular matrix, called extracellular enveloped virus (EEV). Actin tail formation is exploited to enhance spread of VACV via the repulsion of superinfecting virions from infected cells [14,15]
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.
