HIV-1 Nef interacts with LMP7 to attenuate immunoproteasome formation and MHC-I antigen presentation
biorxiv(2019)
摘要
Proteasome is major protein degradation machinery and plays essential roles in diverse biological functions. Upon cytokine inductions, proteasome subunits β1, β2, and β5 are replaced by β1i/LMP2, β2i/MECL-1, and β5i/LMP7, leading to the formation of immunoproteasome. Immunoproteasome-degraded products are loaded onto the major histocompatibility complex class I (MHC-I) to regulate immune responses and induce cytotoxic-T-lymphocytes (CTLs). Human immunodeficiency virus type 1 (HIV-1) is the causal agent of acquired immunodeficiency syndrome (AIDS). HIV-1-specific CTLs represent critical immune responses to limit viral replication. HIV-1 negative regulatory factor (Nef) counteracts host immunity, especially the MHC-I/CTL. This study reveals a distinct mechanism by which Nef facilitates immune evasion through attenuating the functions of immunoproteasome and MHC-I. Nef interacts with LMP7 on the endoplasmic reticulum (ER) to down-regulate the incorporation of LMP7 into immunoproteasome, and thereby attenuating immunoproteasome formation. Moreover, Nef represses immunoproteasome protein degradation function, MHC-I trafficking, and antigen presentation activity.
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关键词
Antigen presentation,Negative regulatory factor,Nef,Human immunodeficiency virus type 1,HIV-1,Immunoproteasome,Major histocompatibility complex class I,MHC-I
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