HIV-1 and HIV-2 infections induce autophagy in Jurkat and CD4+ T cells

Xue Wang; Yamei Gao; Jiying Tan; Krishnakumar Devadas; Viswanath Ragupathy; Kazuyo Takeda; Jiangqin Zhao; Indira Hewlett

doi:10.1016/j.cellsig.2012.02.016

HIV-1 and HIV-2 infections induce autophagy in Jurkat and CD4+ T cells

Cell Signal. 2012 Jul;24(7):1414-9. doi: 10.1016/j.cellsig.2012.02.016. Epub 2012 Mar 2.

Authors

Xue Wang¹, Yamei Gao, Jiying Tan, Krishnakumar Devadas, Viswanath Ragupathy, Kazuyo Takeda, Jiangqin Zhao, Indira Hewlett

Affiliation

¹ Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, United States. xue.wang@fda.hhs.gov

PMID: 22406083
DOI: 10.1016/j.cellsig.2012.02.016

Abstract

Autophagy plays important roles during innate and adaptive immune responses to pathogens, including virus infection. Viruses develop ways to subvert the pathway for their own benefit in order to escape restriction by autophagy, leading to increased viral replication and/or control over apoptosis of their host cells. The effects of HIV infection on the autophagic pathway in host cells have been little documented. Using the susceptible Jurkat cell line and CD4(+) T cells, we studied the relationship of HIV-1 and -2 infections with autophagy. We found that HIV infections significantly increase transcription of ULK1, a member of the autophagy-initiated complex. Two ubiquitin-like conjugation systems, the Atg12 conjugation system and the microtubule-associated protein L chain 3 (LC3) conjugation system that control the elongation of the autophore to form the autophagosome, were activated after HIV infection, with upregulation of Atg12-Atg5 complex and increased transcription of LC3, and formed more autophagosome in infected cells detected using an EM assay. We also found that HIV-1 induced more autophagic death in Jurkat cells relative to HIV-2, and the inhibition of autophagy with 3MA and Beclin-1 knockdown decreased HIV-1 replication significantly. The results indicate that HIV is able to induce the autophagic signaling pathway in HIV-infected host cells, which may be required for HIV infection-mediated apoptotic cell death.

MeSH terms

Adenine / analogs & derivatives
Adenine / pharmacology
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism*
Autophagy / drug effects
Autophagy / genetics*
Autophagy-Related Protein 12
Autophagy-Related Protein 5
Autophagy-Related Protein-1 Homolog
Autophagy-Related Proteins
Beclin-1
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
Cysteine Endopeptidases / metabolism
Gene Expression Regulation
HIV Infections / genetics*
HIV-1 / metabolism
HIV-1 / pathogenicity
HIV-2 / metabolism
HIV-2 / pathogenicity
Humans
Intracellular Signaling Peptides and Proteins / immunology
Intracellular Signaling Peptides and Proteins / metabolism
Jurkat Cells
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / immunology
Microtubule-Associated Proteins / metabolism*
Protein Serine-Threonine Kinases / immunology
Protein Serine-Threonine Kinases / metabolism
RNA, Small Interfering
Signal Transduction
Small Ubiquitin-Related Modifier Proteins / immunology
Small Ubiquitin-Related Modifier Proteins / metabolism
Virus Replication / drug effects

Substances

ATG12 protein, human
ATG5 protein, human
Apoptosis Regulatory Proteins
Autophagy-Related Protein 12
Autophagy-Related Protein 5
Autophagy-Related Proteins
BECN1 protein, human
Beclin-1
Intracellular Signaling Peptides and Proteins
MAP1LC3A protein, human
Membrane Proteins
Microtubule-Associated Proteins
RNA, Small Interfering
Small Ubiquitin-Related Modifier Proteins
3-methyladenine
Autophagy-Related Protein-1 Homolog
Protein Serine-Threonine Kinases
ULK1 protein, human
ATG4D protein, human
Cysteine Endopeptidases
Adenine