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- Title
Retromer Regulates HIV-1 Envelope Glycoprotein Trafficking and Incorporation into Virions.
- Authors
Groppelli, Elisabetta; Len, Alice C.; Granger, Luke A.; Jolly, Clare
- Abstract
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.
- Subjects
GLYCOPROTEINS; HIV; VIRION; ENDOCYTOSIS; VIRAL tropism
- Publication
PLoS Pathogens, 2014, Vol 10, Issue 11, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1004518