title: HIV-1 and HIV-2 infections induce autophagy in Jurkat and CD4+ T cells.
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.
authors.affiliation: 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
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Yamei
authors.initials: Y
authors.lastname: Gao
authors.forename: Jiying
authors.initials: J
authors.lastname: Tan
authors.forename: Krishnakumar
authors.initials: K
authors.lastname: Devadas
authors.forename: Viswanath
authors.initials: V
authors.lastname: Ragupathy
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Takeda
authors.forename: Jiangqin
authors.initials: J
authors.lastname: Zhao
authors.forename: Indira
authors.initials: I
authors.lastname: Hewlett
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D000071189:Autophagy-Related Protein-1 Homolog; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity; D015498:HIV-2 / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: C466624:ATG12 protein, human; C502778:ATG5 protein, human; D051017:Apoptosis Regulatory Proteins; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D047908:Intracellular Signaling Peptides and Proteins; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D025841:Small Ubiquitin-Related Modifier Proteins; C025946:3-methyladenine; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C484754:ULK1 protein, human; C543490:ATG4D protein, human; D003546:Cysteine Endopeptidases; D000225:Adenine