Efficient induction of HIV-1 replication in latently infected cells through contact with CD4+ T cells: involvement of NF-kappaB activation.
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.
Qi
Xiaohua
X
Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Koya
Yoshihiro
Y
Saitoh
Tatsuya
T
Saitoh
Yasunori
Y
Shimizu
Saki
S
Ohba
Kenji
K
Yamamoto
Norio
N
Yamaoka
Shoji
S
Yamamoto
Naoki
N
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
D016328:NF-kappa B