PACS1 is an HIV-1 cofactor that functions in Rev-mediated nuclear export of viral RNA

Hongbing Liu; Pei Wen Hu; Sona Budhiraja; Anisha Misra; Jacob Couturier; Richard E. Lloyd; Dorothy E. Lewis; Jason T. Kimata; Andrew P. Rice

doi:10.1016/j.virol.2019.10.004

PACS1 is an HIV-1 cofactor that functions in Rev-mediated nuclear export of viral RNA

Hongbing Liu, Pei Wen Hu, Sona Budhiraja, Anisha Misra, Jacob Couturier, Richard E. Lloyd, Dorothy E. Lewis, Jason T. Kimata, Andrew P. Rice

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

HIV-1 is dependent upon cellular proteins to mediate the many processes required for viral replication. One such protein, PACS1, functions to localize Furin to the trans-Golgi network where Furin cleaves HIV-1 gp160 Envelope into gp41 and gp120. We show here that PACS1 also shuttles between the nucleus and cytoplasm, associates with the viral Rev protein and its cofactor CRM1, and contributes to nuclear export of viral transcripts. PACS1 appears specific to the Rev-CRM1 pathway and not other retroviral RNA export pathways. Over-expression of PACS1 increases nuclear export of unspliced viral RNA and significantly increases p24 expression in HIV-1-infected Jurkat CD4⁺ T cells. SiRNA depletion and over-expression experiments suggest that PACS1 may promote trafficking of HIV-1 GagPol RNA to a pathway distinct from that of translation on polyribosomes.

Original language	English (US)
Pages (from-to)	88-96
Number of pages	9
Journal	Virology
Volume	540
DOIs	https://doi.org/10.1016/j.virol.2019.10.004
State	Published - Jan 15 2020

Keywords

HIV
PACS
RNA export
Rev
Cell Line
RNA Transport
Cell Nucleus/metabolism
Humans
HIV-1/physiology
Karyopherins/metabolism
Cytoplasm/metabolism
Receptors, Cytoplasmic and Nuclear/metabolism
RNA, Viral/metabolism
Protein Transport
Host-Pathogen Interactions
Vesicular Transport Proteins/metabolism
HIV Infections/metabolism
Virus Replication
Protein Binding
rev Gene Products, Human Immunodeficiency Virus/metabolism

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2019.10.004

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title = "PACS1 is an HIV-1 cofactor that functions in Rev-mediated nuclear export of viral RNA",

abstract = "HIV-1 is dependent upon cellular proteins to mediate the many processes required for viral replication. One such protein, PACS1, functions to localize Furin to the trans-Golgi network where Furin cleaves HIV-1 gp160 Envelope into gp41 and gp120. We show here that PACS1 also shuttles between the nucleus and cytoplasm, associates with the viral Rev protein and its cofactor CRM1, and contributes to nuclear export of viral transcripts. PACS1 appears specific to the Rev-CRM1 pathway and not other retroviral RNA export pathways. Over-expression of PACS1 increases nuclear export of unspliced viral RNA and significantly increases p24 expression in HIV-1-infected Jurkat CD4+ T cells. SiRNA depletion and over-expression experiments suggest that PACS1 may promote trafficking of HIV-1 GagPol RNA to a pathway distinct from that of translation on polyribosomes.",

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author = "Hongbing Liu and Hu, {Pei Wen} and Sona Budhiraja and Anisha Misra and Jacob Couturier and Lloyd, {Richard E.} and Lewis, {Dorothy E.} and Kimata, {Jason T.} and Rice, {Andrew P.}",

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doi = "10.1016/j.virol.2019.10.004",

language = "English (US)",

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T1 - PACS1 is an HIV-1 cofactor that functions in Rev-mediated nuclear export of viral RNA

AU - Liu, Hongbing

AU - Hu, Pei Wen

AU - Budhiraja, Sona

AU - Misra, Anisha

AU - Couturier, Jacob

AU - Lloyd, Richard E.

AU - Lewis, Dorothy E.

AU - Kimata, Jason T.

AU - Rice, Andrew P.

PY - 2020/1/15

Y1 - 2020/1/15

N2 - HIV-1 is dependent upon cellular proteins to mediate the many processes required for viral replication. One such protein, PACS1, functions to localize Furin to the trans-Golgi network where Furin cleaves HIV-1 gp160 Envelope into gp41 and gp120. We show here that PACS1 also shuttles between the nucleus and cytoplasm, associates with the viral Rev protein and its cofactor CRM1, and contributes to nuclear export of viral transcripts. PACS1 appears specific to the Rev-CRM1 pathway and not other retroviral RNA export pathways. Over-expression of PACS1 increases nuclear export of unspliced viral RNA and significantly increases p24 expression in HIV-1-infected Jurkat CD4+ T cells. SiRNA depletion and over-expression experiments suggest that PACS1 may promote trafficking of HIV-1 GagPol RNA to a pathway distinct from that of translation on polyribosomes.

AB - HIV-1 is dependent upon cellular proteins to mediate the many processes required for viral replication. One such protein, PACS1, functions to localize Furin to the trans-Golgi network where Furin cleaves HIV-1 gp160 Envelope into gp41 and gp120. We show here that PACS1 also shuttles between the nucleus and cytoplasm, associates with the viral Rev protein and its cofactor CRM1, and contributes to nuclear export of viral transcripts. PACS1 appears specific to the Rev-CRM1 pathway and not other retroviral RNA export pathways. Over-expression of PACS1 increases nuclear export of unspliced viral RNA and significantly increases p24 expression in HIV-1-infected Jurkat CD4+ T cells. SiRNA depletion and over-expression experiments suggest that PACS1 may promote trafficking of HIV-1 GagPol RNA to a pathway distinct from that of translation on polyribosomes.

KW - HIV

KW - PACS

KW - RNA export

KW - Rev

KW - Cell Line

KW - RNA Transport

KW - Cell Nucleus/metabolism

KW - Humans

KW - HIV-1/physiology

KW - Karyopherins/metabolism

KW - Cytoplasm/metabolism

KW - Receptors, Cytoplasmic and Nuclear/metabolism

KW - RNA, Viral/metabolism

KW - Protein Transport

KW - Host-Pathogen Interactions

KW - Vesicular Transport Proteins/metabolism

KW - HIV Infections/metabolism

KW - Virus Replication

KW - Protein Binding

KW - rev Gene Products, Human Immunodeficiency Virus/metabolism

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JO - Virology

JF - Virology

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PACS1 is an HIV-1 cofactor that functions in Rev-mediated nuclear export of viral RNA

Abstract

Keywords

ASJC Scopus subject areas

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