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The downregulation of CD4 and MHC‐I by primate lentiviruses: a paradigm for the modulation of cell surface receptors
Author(s) -
Piguet Vincent,
Schwartz Olivier,
Gall Sylvie,
Trono Didier
Publication year - 1999
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.1999.tb01282.x
Subject(s) - biology , downregulation and upregulation , microbiology and biotechnology , major histocompatibility complex , tetherin , mhc class i , clathrin , receptor , endoplasmic reticulum , immune system , virology , immunology , endocytosis , viral replication , virus , genetics , gene
Summary: The human and simian immunodeficiency viruses (HIV and SIV) downregulate the cell surface expression of CD4. their primary receptor, and of class I histocompatibility complex (MHC‐I), a critical mediator of immune recognition. While the first of these effects seems important to preserve viral infectivity, the second likely promotes immune evasion. Three HIV‐1 proteins, Nef, Env and Vpu, contribute Eo downregulate CD4. Env forms a complex with CD+ in the endoplasmic reticulum, thereby retaining the receptor in this compartment. Nef and Vpu, on the other hand, act as connectors between CD4 and specific intracellular trafficking pathways, targeting the receptor for degradation in the lysosome and the proteasome, respectively. Some of the downstream partners of the viral proteins in these events have been identified, and include the adaptor complex of clathrin‐coated pits, the β subunit of COP‐I coatomer, and the ubiquitin pathway‐related h‐βTrCP protein. HIV‐induced MHC‐I downregulation, mostly the effect of Nef, also reflects a redistribution of this receptor, with its accumulation in the Golgi. The modalities of this process, however, are as yet imperfectly understood. New evidence indicates that the mechanisms employed by primate lentiviruses to downmodulate CD4 and MHC‐I are also exploited by a number of cellular regulatory processes.