NF-IL6 (C/EBPbeta) induces HIV-1 replication by inhibiting cytidine deaminase APOBEC3G.
T cell activation is crucial for the productive HIV-1 infection of primary T cells; however, little is known about the host molecules involved in this process. We show that the host transcription factor NF-IL6 (also called C/EBPbeta) renders primary CD4(+) T cells highly permissive for HIV-1 replication. NF-IL6 facilitates reverse transcription of the virus by binding to and inhibiting the antiviral cytidine deaminase APOBEC3G. A mutation in NF-IL6 at Ser-288 weakened its binding to APOBEC3G and strongly inhibited HIV-1 replication. NF-IL6 also induced the replication of a Vif-deficient strain of HIV-1 in nonpermissive HUT78 cells. These data indicate that NF-IL6 is a natural inhibitor of APOBEC3G that facilitates HIV-1 replication. Host factors, such as NF-IL6, that are involved in early HIV-1 replication are potential targets for anti-HIV-1 therapy. Our findings shed light on the activation of HIV-1 replication by T cell host molecules and reveal a unique regulation of DNA deamination by APOBEC3G and NF-IL6.
Kinoshita
Shigemi M
SM
Laboratory of Combined Research on Microbiology and Immunology, Research Institute of Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. shigemik@biken.osaka-u.ac.jp
Taguchi
Shizuka
S
D000071480:APOBEC-3G Deaminase; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000821:virology*; D002460:Cell Line; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D014779:Virus Replication
D022782:CCAAT-Enhancer-Binding Protein-beta; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase