HIV-1 envelope proteins up-regulate N 6 -methyladenosine levels of cellular RNA independently of viral replication

Nagaraja Tirumuru; Li Wu

doi:10.1074/jbc.ra118.005608

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HIV-1 envelope proteins up-regulate N 6 -methyladenosine levels of cellular RNA independently of viral replication

Journal article

Open access

Peer reviewed

HIV-1 envelope proteins up-regulate N 6 -methyladenosine levels of cellular RNA independently of viral replication

Nagaraja Tirumuru and Li Wu

The Journal of biological chemistry, Vol.294(9), pp.3249-3260

03/01/2019

DOI: 10.1074/jbc.ra118.005608

PMCID: PMC6398121

PMID: 30617182

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Abstract

-methyladenosine (m A) modification of HIV-1 RNA regulates viral replication and protein expression. The m A modification is regulated by two groups of cellular proteins named writers and erasers that add or remove m A, respectively. HIV-1 infection of CD4 T-cells increases m A levels of cellular mRNA, but the underlying mechanism is unknown. Here, we show that HIV-1 infection of CD4 primary T-cells or Jurkat cells significantly increases m A levels of cellular RNA independently of viral replication. Compared with HIV-1-infected CD4 T-cells, similar m A up-regulation was detected in total RNA from HIV-1-infected cells treated with a reverse-transcriptase inhibitor or with heat-inactivated HIV-1. Compared with mock controls, significantly increased m A levels were detected in total RNA from Jurkat cells infected by single-cycle HIV-1 pseudotyped with an HIV-1 envelope (Env) glycoprotein, but not with vesicular stomatitis virus glycoprotein G (VSV-G). Overexpression of HIV-1 Env in HEK293T cells did not affect m A levels of cellular RNA, suggesting that synthesis of Env is not required for m A up-regulation. Interestingly, treatment of Jurkat cells with recombinant gp120 of HIV-1 Env significantly increased m A levels of cellular RNA, which was reduced by a gp120-neutralizing antibody. Preincubation of Jurkat cells with a CD4 receptor-neutralizing antibody blocked HIV-1-induced up-regulation of m A levels in cellular RNA. Moreover, HIV-1 infection or gp120 treatment did not alter the protein expression of m A writers and erasers in cells. Our findings suggest that HIV-1 gp120 binding to the CD4 receptor is required for m A up-regulation in cells.

HIV-1 - metabolism

Up-Regulation

Jurkat Cells

Humans

HIV-1 - genetics

HIV Envelope Protein gp120 - metabolism

HIV-1 - physiology

Virus Replication

Adenosine - analogs & derivatives

HEK293 Cells

Viral Envelope Proteins - metabolism

Adenosine - metabolism

CD4-Positive T-Lymphocytes - virology

RNA - metabolism

Details

Title: Subtitle: HIV-1 envelope proteins up-regulate N 6 -methyladenosine levels of cellular RNA independently of viral replication
Creators: Nagaraja Tirumuru - the Center for RNA Biology, Ohio State University, Columbus, Ohio 43210
Li Wu - the Center for RNA Biology, Ohio State University, Columbus, Ohio 43210
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.294(9), pp.3249-3260
DOI: 10.1074/jbc.ra118.005608
PMID: 30617182
PMCID: PMC6398121
NLM abbreviation: J Biol Chem
ISSN: 1083-351X
eISSN: 1083-351X
Publisher: United States
Grant note: R01 GM128212 / NIGMS NIH HHS R01 AI150343 / NIAID NIH HHS
Language: English
Date published: 03/01/2019
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001111402771

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