title: Efficient induction of HIV-1 replication in latently infected cells through contact with CD4+ T cells: involvement of NF-kappaB activation.
abstract: Reservoir cells latently infected with HIV-1 pose one of the major obstacles that hamper ultimate eradication of HIV-1 from infected patients. In this report, we showed that direct contact with MOLT-4 T cells induced HIV-1 replication in J(22)-HL-60 latently infected cells without any additional stimulus. Neutralization experiments revealed that pro-inflammatory cytokines, whose production was increased following cell-cell contact, were unlikely to be primarily involved in the induced HIV-1 replication. Cell-cell contact, but not soluble components in the culture supernatant, caused a rapid phosphorylation and degradation of IkappaBalpha, which led to elevated NF-kappaB DNA binding activity in J(22)-HL-60 cells. Furthermore, forced expression of a super-repressor form of IkappaBalpha or pretreatment with ritonavir efficiently blocked the activation of NF-kappaB and HIV-1 replication in J(22)-HL-60 cells co-cultured with MOLT-4 T cells. Moreover, either resting or PHA stimulated primary CD4(+) T cells induced HIV-1 replication in J(22)-HL-60 cells in a similar way with that of MOLT-4 cells. These results indicated that direct contact with CD4(+) T cells induced HIV-1 replication in latently infected cells and provide insight into the molecular mechanism of virus release from myeloid progenitor cells latently infected with HIV-1.
authors.affiliation: Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Qi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Koya
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saitoh
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Saitoh
authors.forename: Saki
authors.initials: S
authors.lastname: Shimizu
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohba
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamaoka
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002450:Cell Communication; D002460:Cell Line; D018920:Coculture Techniques; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D016328:NF-kappa B