The TRIM Family Protein KAP1 Inhibits HIV-1 Integration

Awatef Allouch, et al. Cell. (2011) 9: 484–495

Speaker: Pin-Hung Lin (林品宏)                                          Time: 13:10~14:00 Feb. 29, 2012

Commentator: Shainn-Wei Wang, Ph.D. (王憲威老師)   )       Place: Room 601

Abstract

In human immunodeficiency virus 1 (HIV-1) infection, virus hijacks cellular proteins and cellular pathways to complete the different steps of life cycle. The integration of viral cDNA into the host genome is a key step for HIV-1 infection. During integration, integrase(IN) associates with cellular proteins to modify viral cDNA before integrating viral cDNA into the host genome in the nucleoplasm ¹. Previous studies have shown that IN activity is positively regulated by cellular histone acetyl transferase (HAT) p300 ². However, cellular proteins that inhibit HIV-1 integration by regulating IN activity remain unclear. In this study, the authors found that KAP1, a protein in the TRIM family, selectively bound to acetylated IN. KAP1 overexpressing inhibited HIV-1 replication by specifically downregulatingthe efficiency of integration event. Moreover, inhibition of KAP1 in HIV-1 integration was dependent on integrase lysines which was acetylated by p300 and occurred in different cell types including T cells. They further found that KAP1 inhibited viral integration by recruiting NuRD histone deacetylase 1 (HDAC1) to induce IN deacetylation. In KAP1 overexpression cells, blocking HDAC1 increased integrated viral cDNA. Collectively, KAP1 inhibits HIV-1 integration by interacting with acetylated IN and by recruiting HDAC1 to reduce IN activity.  

References:

1.      Youichi Suzuki and Robert Craigie. The road to chromatin-nuclear entry of retroviruses. Nature (2007) 5:187-196.

2.      Katrien Busschots et al. Cellular co-factors of HIV-1 integration. TRENDS in Biochemical Sciences (2010) 31:98-105.