tailieunhanh - Báo cáo y học: " HIV-1 Accessory Protein Vpr: Relevance in the pathogenesis of HIV and potential for therapeutic interventio"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: HIV-1 Accessory Protein Vpr: Relevance in the pathogenesis of HIV and potential for therapeutic intervention. | Kogan and Rappaport Retrovirology 2011 8 25 http content 8 1 25 RETROVIROLOGY REVIEW Open Access HIV-1 Accessory Protein Vpr Relevance in the pathogenesis of HIV and potential for therapeutic intervention Michael Kogan and Jay Rappaport Abstract The HIV protein Vpr is a multifunctional accessory protein critical for efficient viral infection of target CD4 T cells and macrophages. Vpr is incorporated into virions and functions to transport the preintegration complex into the nucleus where the process of viral integration into the host genome is completed. This action is particularly important in macrophages which as a result of their terminal differentiation and non-proliferative status would be otherwise more refractory to HIV infection. Vpr has several other critical functions including activation of HIV-1 LTR transcription cell-cycle arrest due to DCAF-1 binding and both direct and indirect contributions to T-cell dysfunction. The interactions of Vpr with molecular pathways in the context of macrophages on the other hand support accumulation of a persistent reservoir of HIV infection in cells of the myeloid lineage. The role of Vpr in the virus life cycle as well as its effects on immune cells appears to play an important role in the immune pathogenesis of AIDS and the development of HIV induced end-organ disease. In view of the pivotal functions of Vpr in virus infection replication and persistence of infection this protein represents an attractive target for therapeutic intervention. Introduction Human immunodeficiency virus type 1 HIV-1 is a len-tiviral family member that encodes retroviral Gag Pol and Env proteins along with six additional accessory proteins Tat Rev Vpu Vif Nef and Vpr. Viral protein R Vpr is a 96 amino acid 14 kDa protein that was originally isolated almost two decades ago 1 2 and is highly conserved in both HIV-1 and simian immunodeficiency virus SIV 3-5 . Numerous investigations over the last 20 years have shown that