Non-POU Domain-Containing Octamer-Binding Protein Negatively Regulates HIV-1 Infection in CD4(+) T Cells

Corine St Gelais; Jonathan Roger; Li Wu

doi:10.1089/AID.2014.0313

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Non-POU Domain-Containing Octamer-Binding Protein Negatively Regulates HIV-1 Infection in CD4(+) T Cells

Journal article

Open access

Peer reviewed

Non-POU Domain-Containing Octamer-Binding Protein Negatively Regulates HIV-1 Infection in CD4(+) T Cells

Corine St Gelais, Jonathan Roger and Li Wu

AIDS research and human retroviruses, Vol.31(8), pp.806-816

08/2015

DOI: 10.1089/AID.2014.0313

PMCID: PMC4533096

PMID: 25769457

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Abstract

HIV-1 interacts with numerous cellular proteins during viral replication. Identifying such host proteins and characterizing their roles in HIV-1 infection can deepen our understanding of the dynamic interplay between host and pathogen. We previously identified non-POU domain-containing octamer-binding protein (NonO or p54nrb) as one of host factors associated with catalytically active preintegration complexes (PIC) of HIV-1 in infected CD4(+) T cells. NonO is involved in nuclear processes including transcriptional regulation and RNA splicing. Although NonO has been identified as an HIV-1 interactant in several recent studies, its role in HIV-1 replication has not been characterized. We investigated the effect of NonO on the HIV-1 life cycle in CD4(+) T cell lines and primary CD4(+) T cells using single-cycle and replication-competent HIV-1 infection assays. We observed that short hairpin RNA (shRNA)-mediated stable NonO knockdown in a CD4(+) Jurkat T cell line and primary CD4(+) T cells did not affect cell viability or proliferation, but enhanced HIV-1 infection. The enhancement of HIV-1 infection in Jurkat T cells correlated with increased viral reverse transcription and gene expression. Knockdown of NonO expression in Jurkat T cells modestly enhanced HIV-1 gag mRNA expression and Gag protein synthesis, suggesting that viral gene expression and RNA regulation are the predominantly affected events causing enhanced HIV-1 replication in NonO knockdown (KD) cells. Furthermore, overexpression of NonO in Jurkat T cells reduced HIV-1 single-cycle infection by 41% compared to control cells. Our data suggest that NonO negatively regulates HIV-1 infection in CD4(+) T cells, albeit it has modest effects on early and late stages of the viral life cycle, highlighting the importance of host proteins associated with HIV-1 PIC in regulating viral replication.

Octamer Transcription Factors - antagonists & inhibitors

Humans

Cells, Cultured

Nuclear Matrix-Associated Proteins - metabolism

Gene Knockdown Techniques

CD4-Positive T-Lymphocytes - immunology

Host-Pathogen Interactions

HIV-1 - immunology

HIV-1 - physiology

Virus Replication

Nuclear Matrix-Associated Proteins - antagonists & inhibitors

CD4-Positive T-Lymphocytes - virology

Octamer Transcription Factors - metabolism

RNA-Binding Proteins - metabolism

RNA-Binding Proteins - antagonists & inhibitors

Details

Title: Subtitle: Non-POU Domain-Containing Octamer-Binding Protein Negatively Regulates HIV-1 Infection in CD4(+) T Cells
Creators: Corine St Gelais - 1 Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University , Columbus, Ohio
Jonathan Roger - 1 Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University , Columbus, Ohio
Li Wu - 3 Comprehensive Cancer Center, The Ohio State University , Columbus, Ohio
Resource Type: Journal article
Publication Details: AIDS research and human retroviruses, Vol.31(8), pp.806-816
DOI: 10.1089/AID.2014.0313
PMID: 25769457
PMCID: PMC4533096
NLM abbreviation: AIDS Res Hum Retroviruses
ISSN: 0889-2229
eISSN: 1931-8405
Publisher: United States
Grant note: R21 AI102822 / NIAID NIH HHS R01 AI104483 / NIAID NIH HHS AI104483 / NIAID NIH HHS AI102822 / NIAID NIH HHS
Language: English
Date published: 08/2015
Academic Unit: Microbiology and Immunology
Record Identifier: 9984002384002771

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