Kinoshita S, Su L, Amano M, Timmerman L A, Kaneshima H, Nolan G P
Department of Molecular Pharmacology, Stanford University School of Medicine, California 94305, USA.
Immunity. 1997 Mar;6(3):235-44. doi: 10.1016/s1074-7613(00)80326-x.
Clinical deterioration in human immunodeficiency virus type 1 (HIV-1) infection is associated with increased levels of viral replication and burden in the peripheral blood and lymphoid organs. T cell activation and ensuing cellular gene activation can be critical for HIV-1 replication. The hypothesis that the nuclear factor of activated T cells (NF-AT) may influence HIV-1 replication is therefore compelling given the tight correlation of HIV-1 transcriptional induction to T cell activation. We report that certain NF-AT(Rel) family members productively bind the kappaB regulatory elements, synergize with NF-kappaB and Tat in transcriptional activation of HIV-1, and enhance HIV-1 replication in T cells. These results link regulatory factors critical to T cell commitment directly to HIV-1 replication.
1型人类免疫缺陷病毒(HIV-1)感染中的临床病情恶化与外周血和淋巴器官中病毒复制水平及病毒载量的增加有关。T细胞活化以及随之而来的细胞基因活化对于HIV-1复制可能至关重要。鉴于HIV-1转录诱导与T细胞活化密切相关,因此活化T细胞核因子(NF-AT)可能影响HIV-1复制这一假说颇具说服力。我们报告称,某些NF-AT(Rel)家族成员能有效结合κB调控元件,在HIV-1的转录激活过程中与NF-κB和Tat协同作用,并增强HIV-1在T细胞中的复制。这些结果将对T细胞定向分化至关重要的调控因子直接与HIV-1复制联系起来。