Okamoto H, Asamitsu K, Nishimura H, Kamatani N, Okamoto T
Department of Molecular Genetics, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.
Biochem Biophys Res Commun. 2000 Dec 20;279(2):494-9. doi: 10.1006/bbrc.2000.3972.
HIV-1 is the etiologic agent of acquired immune deficiency syndrome (AIDS). Functional loss of antigen-presenting cells (APC) in HIV-1 infection is considered to be involved in AIDS pathogenesis. We found that actions of the viral transactivator Tat and the transactivator of MHC class II genes, CIITA, are mutually inhibitory. While Tat inhibited expression of MHC class II genes in APC, overexpression of CIITA inhibited Tat and subsequently HIV-1 replication. This action of Tat appears to be mediated by sequestering the common cofactor, cyclin T1, but not p300 and CBP. These reciprocal actions between Tat and CIITA not only explains the functional impairment of APC in HIV-1 infection but also rationalizes the suppression of HIV-1 virus load by induction of CIITA such as IFN-gamma.
人类免疫缺陷病毒1型（HIV-1）是获得性免疫缺陷综合征（AIDS）的病原体。HIV-1感染中抗原呈递细胞（APC）的功能丧失被认为与AIDS发病机制有关。我们发现病毒反式激活因子Tat与MHC II类基因反式激活因子CIITA的作用相互抑制。Tat抑制APC中MHC II类基因的表达，而CIITA的过表达则抑制Tat并随后抑制HIV-1复制。Tat的这种作用似乎是通过隔离共同辅因子细胞周期蛋白T1介导的，而不是p300和CBP。Tat和CIITA之间的这些相互作用不仅解释了HIV-1感染中APC的功能损害，也使通过诱导CIITA（如干扰素-γ）来抑制HIV-1病毒载量变得合理。
