Function
Vpr protein (Vpr) or viral protein R is a 96 amino acid protein which encoded by the human Immunodeficiency virus type 1 (HIV-1). HIV-1 genome includes nine genes, six of them are accessory proteins, including vpr. Vpr has several roles in the progression of acquired immunodeficiency syndrome (AIDS) disease, including regulation the HIV-1 pre-integration complex (PIC) nuclear import and virus replication in non-dividing macrophages[1]. Moreover, Vpr prevents mitosis of dividing infect cells by blockade at G2 phase, when the viral promoter is more active, and induced apoptosis of these cells in G1 and M phase. Both the activities of cell cycle arrest and induce apoptosis has proven to be independence by mutations that can cause only one of these affects[2].
Disease
HIV-1 retrovirus is the cause of AIDS disease. HIV-1 is a RNA virus which copy its genome to the host-cell genome in infect cells. HIV-1 infects activated CD4 immune cells and macrophages. When the disease is expressing in carriers, the progressive depletion of CD4 T cells causes immunodeficiency[3].
For more details about AIDS disease see AIDS in Wikipedia
For details about another HIV-1 components and its replication pathway see HIV and accessory proteins.
Relevance
Understanding of Vpr structure and molecular mechanism may facilitate the design of HIV-1 antiviral therapy by its inhibition. Deletion of both vpr and vpx genes in SIV, which their protein products in SIV combine Vpr function in HIV-1, eliminate virus replication[3]. The multiple significant functions that Vpr fills in HIV-1 replication makes it an attractive candidate for antiviral therapy [2]
Conservation
Vpr is highly conserved in HIV and simian immunodeficiency virus (SIV), similar retrovirus which infects non-human primates[1]. In addition, all primate lentiviruses has vpr gene whose protein product has highly conserved motifs. HIV-2 and SIVsm lentiviruses have additionally gene - vpx. In these lentiviruses, vpr and vpx executes together the roles which HIV-1 vpr perform. Vpr and Vpx has low conservation between them.
- ↑ 1.0 1.1 Morellet N, Bouaziz S, Petitjean P, Roques BP. NMR structure of the HIV-1 regulatory protein VPR. J Mol Biol. 2003 Mar 14;327(1):215-27. PMID:12614620
- ↑ 2.0 2.1 Gonzalez ME. The HIV-1 Vpr Protein: A Multifaceted Target for Therapeutic Intervention. Int J Mol Sci. 2017 Jan 10;18(1). pii: ijms18010126. doi: 10.3390/ijms18010126. PMID:28075409 doi:https://dx.doi.org/10.3390/ijms18010126
- ↑ 3.0 3.1 Emerman M. HIV-1, Vpr and the cell cycle. Curr Biol. 1996 Sep 1;6(9):1096-103. PMID:8805364