Abstract
The assembly and release of retroviruses from the host cells requires a coordinated series of interactions between viral structural proteins and cellular trafficking pathways. Although a number of cellular factors involved in retrovirus assembly have been identified, it is likely that retroviruses utilize additional trafficking factors to expedite their assembly and budding that have not yet been defined. We performed a screen using an siRNA library targeting host membrane trafficking genes in order to identify new host factors that contribute to retrovirus assembly or release. We utilized two retroviruses that follow very distinct assembly pathways, HIV-1 and Mason-Pfizer monkey virus (M-PMV) in order to identify host pathways that are generally applicable in retrovirus assembly versus those that are unique to HIV or M-PMV. Here we report the identification of 24 host proteins identified in the screen and subsequently validated in follow-up experiments as contributors to the assembly or release of both viruses. In addition to identifying a number of previously unsuspected individual trafficking factors, we noted multiple hits among proteins involved in modulation of the actin cytoskeleton, clathrin-mediated transport pathways, and phosphoinositide metabolism. Our study shows that distant genera of retroviruses share a number of common interaction strategies with host cell trafficking machinery, and identifies new cellular factors involved in the late stages of retroviral replication.
Highlights
Retroviruses assemble capsids and bud from cellular membranes by following one of two distinct morphogenetic pathways [1,2]
Results small-interfering RNA (siRNA) screen To identify human cellular factors required for human immunodeficiency virus type 1 (HIV-1) and M
The use of small-interfering RNA screens has greatly extended our knowledge of the cellular factors hijacked by viruses for productive replication
Summary
Retroviruses assemble capsids and bud from cellular membranes by following one of two distinct morphogenetic pathways [1,2]. The first pathway is designated the type B/D pathway, in which immature cores assemble in the cytoplasm of cells and subsequently are transported to the plasma membrane for envelopment and budding. The second pathway is the C-type pathway, in which viral components assemble on the plasma membrane, with simultaneous assembly of the immature capsid shell and acquisition of the lipid envelope. The process of envelopment and budding of retroviral capsids at the plasma membrane includes common features and is likely to involve host factors that are common to retroviruses following either pathway
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