The Vif and Vpr accessory proteins independently cause HIV-1-induced T cell cytopathicity and cell cycle arrest.

@article{citeulike:3024774, abstract = {HIV type I (HIV-1) can cause G(2) cell cycle arrest and death of CD4(+) T lymphocytes in vitro and inexorable depletion of these cells in vivo. However, the molecular mechanism of viral cytopathicity has not been satisfactorily elucidated. Previously, we showed that HIV-1 kills T cells by a necrotic form of cell death that requires high level expression of an integrated provirus but not the env or nef genes. To determine which viral protein(s) are required for cell death, we systematically mutated, alone and in combination, the ORFs of the NL4-3 strain of HIV-1. We found that the elimination of the viral functions encoded by gag-pol and vpu, tat, and rev did not mitigate cytopathicity. However, elimination of the vif and vpr accessory genes together, but not individually, renders the virus incapable of causing cell death and G(2) cell cycle blockade. We thus identify vif and vpr as necessary for T cell cytopathic effects induced by HIV-1. These findings may provide an important insight into the molecular mechanism of viral pathogenesis in AIDS.}, address = {Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA.}, author = {Sakai, K. and Dimas, J. and Lenardo, M. J. }, citeulike-article-id = {3024774}, doi = {http://dx.doi.org/10.1073/pnas.0509417103}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {vif, vpr}, month = {February}, number = {9}, pages = {3369--3374}, posted-at = {2008-07-21 16:53:45}, priority = {2}, title = {The Vif and Vpr accessory proteins independently cause HIV-1-induced T cell cytopathicity and cell cycle arrest.}, url = {http://dx.doi.org/10.1073/pnas.0509417103}, volume = {103}, year = {2006} }

TY - JOUR ID - citeulike:3024774 L3 - citeulike-article-id:3024774 TI - The Vif and Vpr accessory proteins independently cause HIV-1-induced T cell cytopathicity and cell cycle arrest. JF - Proceedings of the National Academy of Sciences of the United States of America VL - 103 IS - 9 SP - 3369 EP - 3374 AD - Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA. SN - 0027-8424 N2 - HIV type I (HIV-1) can cause G(2) cell cycle arrest and death of CD4(+) T lymphocytes in vitro and inexorable depletion of these cells in vivo. However, the molecular mechanism of viral cytopathicity has not been satisfactorily elucidated. Previously, we showed that HIV-1 kills T cells by a necrotic form of cell death that requires high level expression of an integrated provirus but not the env or nef genes. To determine which viral protein(s) are required for cell death, we systematically mutated, alone and in combination, the ORFs of the NL4-3 strain of HIV-1. We found that the elimination of the viral functions encoded by gag-pol and vpu, tat, and rev did not mitigate cytopathicity. However, elimination of the vif and vpr accessory genes together, but not individually, renders the virus incapable of causing cell death and G(2) cell cycle blockade. We thus identify vif and vpr as necessary for T cell cytopathic effects induced by HIV-1. These findings may provide an important insight into the molecular mechanism of viral pathogenesis in AIDS. KW - vif KW - vpr AU - Sakai, K AU - Dimas, J AU - Lenardo, MJ PY - 2006/02/28/ UR - http://dx.doi.org/10.1073/pnas.0509417103 ER -