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

PLoS Pathogens

Luke A. Granger¹  Alice C. Len¹  Clare Jolly¹  Elisabetta Groppelli¹ 

[1] Division of Infection and Immunity, University College London, London, United Kingdom

关键词: HIV-1;    Cell membranes;    Virions;    Membrane proteins;    Small interfering RNAs;    Membrane trafficking;    HeLa cells;    Cell staining;   

DOI  :  10.1371/journal.ppat.1004518

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY