HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation

ABSTRACT The proteasome is a major protein degradation machinery with essential and diverse biological functions. Upon induction by cytokines, proteasome subunits β1, β2, and β5 are replaced by β1i/LMP2, β2i/MECL-1, and β5i/LMP7, resulting in the formation of an immunoproteasome (iProteasome). iProt...

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Autores principales:	Yang Yang, Weiyong Liu, Dan Hu, Rui Su, Man Ji, Yuqing Huang, Muhammad Adnan Shereen, Xiaodi Xu, Zhen Luo, Qi Zhang, Fang Liu, Kailang Wu, Yingle Liu, Jianguo Wu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	antigen presentation negative regulatory factor Nef human immunodeficiency virus type 1 HIV-1 immunoproteasome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/404e539f56f84faa84ded3dee8e86445
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spelling	oai:doaj.org-article:404e539f56f84faa84ded3dee8e864452021-11-15T16:19:07ZHIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation10.1128/mBio.02221-192150-7511https://doaj.org/article/404e539f56f84faa84ded3dee8e864452020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02221-19https://doaj.org/toc/2150-7511ABSTRACT The proteasome is a major protein degradation machinery with essential and diverse biological functions. Upon induction by cytokines, proteasome subunits β1, β2, and β5 are replaced by β1i/LMP2, β2i/MECL-1, and β5i/LMP7, resulting in the formation of an immunoproteasome (iProteasome). iProteasome-degraded products are loaded onto the major histocompatibility complex class I (MHC-I), regulating immune responses and inducing cytotoxic T lymphocytes (CTLs). Human immunodeficiency virus type 1 (HIV-1) is the causal agent of AIDS. HIV-1-specific CTLs represent a critical immune mechanism limiting viral replication. HIV-1 negative regulatory factor (Nef) counteracts host immunity, particularly the response involving MHC-I/CTL. This study identifies a distinct mechanism by which Nef facilitates immune evasion via suppressing the function of iProteasome and MHC-I. Nef interacts with LMP7 on the endoplasmic reticulum (ER), downregulating the incorporation of LMP7 into iProteasome and thereby attenuating its formation. Moreover, Nef represses the iProteasome function of protein degradation, MHC-I trafficking, and antigen presentation. IMPORTANCE The ubiquitin-proteasome system (UPS) is essential for the degradation of damaged proteins, which takes place in the proteasome. Upon activation by cytokines, the catalytic subunits of the proteasome are replaced by distinct isoforms resulting in the formation of an immunoproteasome (iProteasome). iProteasome generates peptides used by major histocompatibility complex class I (MHC-I) for antigen presentation and is essential for immune responses. HIV-1 is the causative agent of AIDS, and HIV-1-specific cytotoxic T lymphocytes (CTLs) provide immune responses limiting viral replication. This study identifies a distinct mechanism by which HIV-1 promotes immune evasion. The viral protein negative regulatory factor (Nef) interacts with a component of iProteasome, LMP7, attenuating iProteasome formation and protein degradation function, and thus repressing the MHC-I antigen presentation activity of MHC-I. Therefore, HIV-1 targets LMP7 to inhibit iProteasome activation, and LMP7 may be used as the target for the development of anti-HIV-1/AIDS therapy.Yang YangWeiyong LiuDan HuRui SuMan JiYuqing HuangMuhammad Adnan ShereenXiaodi XuZhen LuoQi ZhangFang LiuKailang WuYingle LiuJianguo WuAmerican Society for Microbiologyarticleantigen presentationnegative regulatory factorNefhuman immunodeficiency virus type 1HIV-1immunoproteasomeMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	antigen presentation negative regulatory factor Nef human immunodeficiency virus type 1 HIV-1 immunoproteasome Microbiology QR1-502
spellingShingle	antigen presentation negative regulatory factor Nef human immunodeficiency virus type 1 HIV-1 immunoproteasome Microbiology QR1-502 Yang Yang Weiyong Liu Dan Hu Rui Su Man Ji Yuqing Huang Muhammad Adnan Shereen Xiaodi Xu Zhen Luo Qi Zhang Fang Liu Kailang Wu Yingle Liu Jianguo Wu HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation
description	ABSTRACT The proteasome is a major protein degradation machinery with essential and diverse biological functions. Upon induction by cytokines, proteasome subunits β1, β2, and β5 are replaced by β1i/LMP2, β2i/MECL-1, and β5i/LMP7, resulting in the formation of an immunoproteasome (iProteasome). iProteasome-degraded products are loaded onto the major histocompatibility complex class I (MHC-I), regulating immune responses and inducing cytotoxic T lymphocytes (CTLs). Human immunodeficiency virus type 1 (HIV-1) is the causal agent of AIDS. HIV-1-specific CTLs represent a critical immune mechanism limiting viral replication. HIV-1 negative regulatory factor (Nef) counteracts host immunity, particularly the response involving MHC-I/CTL. This study identifies a distinct mechanism by which Nef facilitates immune evasion via suppressing the function of iProteasome and MHC-I. Nef interacts with LMP7 on the endoplasmic reticulum (ER), downregulating the incorporation of LMP7 into iProteasome and thereby attenuating its formation. Moreover, Nef represses the iProteasome function of protein degradation, MHC-I trafficking, and antigen presentation. IMPORTANCE The ubiquitin-proteasome system (UPS) is essential for the degradation of damaged proteins, which takes place in the proteasome. Upon activation by cytokines, the catalytic subunits of the proteasome are replaced by distinct isoforms resulting in the formation of an immunoproteasome (iProteasome). iProteasome generates peptides used by major histocompatibility complex class I (MHC-I) for antigen presentation and is essential for immune responses. HIV-1 is the causative agent of AIDS, and HIV-1-specific cytotoxic T lymphocytes (CTLs) provide immune responses limiting viral replication. This study identifies a distinct mechanism by which HIV-1 promotes immune evasion. The viral protein negative regulatory factor (Nef) interacts with a component of iProteasome, LMP7, attenuating iProteasome formation and protein degradation function, and thus repressing the MHC-I antigen presentation activity of MHC-I. Therefore, HIV-1 targets LMP7 to inhibit iProteasome activation, and LMP7 may be used as the target for the development of anti-HIV-1/AIDS therapy.
format	article
author	Yang Yang Weiyong Liu Dan Hu Rui Su Man Ji Yuqing Huang Muhammad Adnan Shereen Xiaodi Xu Zhen Luo Qi Zhang Fang Liu Kailang Wu Yingle Liu Jianguo Wu
author_facet	Yang Yang Weiyong Liu Dan Hu Rui Su Man Ji Yuqing Huang Muhammad Adnan Shereen Xiaodi Xu Zhen Luo Qi Zhang Fang Liu Kailang Wu Yingle Liu Jianguo Wu
author_sort	Yang Yang
title	HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation
title_short	HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation
title_full	HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation
title_fullStr	HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation
title_full_unstemmed	HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation
title_sort	hiv-1 nef interacts with lmp7 to attenuate immunoproteasome formation and major histocompatibility complex class i antigen presentation
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/404e539f56f84faa84ded3dee8e86445
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HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation

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