Retromer Regulates HIV-1 Envelope Glycoprotein Trafficking and Incorporation into Virions

The envelope glycoprotein (env) of the human immunodeficiency virus type-1 (hiv-1) is a critical determinant of viral infectivity,tropism and is the main target for humoral immunity; however,little is known about the cellular machinery that directs env trafficking and its incorporation into nascent virions. here we identify the mammalian retromer complex as a novel and important cellular factor regulating env trafficking. retromer mediates endosomal sorting and is most closely associated with endosome-to-golgi transport. consistent with this function,inactivating retromer using rnai targeting the cargo selective trimer complex inhibited retrograde trafficking of endocytosed env to the golgi. notably,in hiv-1 infected cells,inactivating retromer modulated plasma membrane expression of env,along with env incorporation into virions and particle infectivity. mutagenesis studies coupled with coimmunoprecipitations revealed that retromer-mediated trafficking requires the env cytoplasmic tail that we show binds directly to retromer components vps35 and vps26. taken together these results provide novel insight into regulation of hiv-1 env trafficking and infectious hiv-1 morphogenesis and show for the first time a role for retromer in the late-steps of viral replication and assembly of a virus. © 2014 groppelli et al.