APOBEC3G-independent reduction in virion infectivity during long-term HIV-1 replication in terminally differentiated macrophages Export

@article{citeulike:3194335, abstract = {APOBEC3G (APO3G) is a cellular cytidine deaminase with potent antiviral activity. In the case of HIV, the antiviral activity of APO3G is counteracted by the viral Vif protein. Monocyte-derived macrophages (MDM) are terminally differentiated, non-dividing cells susceptible to HIV infection. Human MDM are known to express APO3G and HIV replication in these cells is dependent on Vif. Here we analyzed the correlation between HIV-1 replication and APO3G expression in MDM. Replication of wild type HIV-1 induced a gradual 4-5-fold reduction in APO3G expression. The efficiency of APO3G downregulation correlated with the efficiency of virus replication. Interestingly, despite downregulation of APO3G, the relative infectivity of viruses rapidly declined during the course of infection and was already reduced \~{} 90\% prior to peak virus production. Cell-free virus preparations showed increased levels of a 41 kDa MA-CA processing intermediate. Sequence analysis around the MA-CA cleavage site and the protease and LTR regions did not reveal deaminase-induced hypermutation of the viral genome, suggesting that APO3G activity is not responsible for the incomplete Gag processing. Thus, the loss of infectivity of HIV-1 viruses produced from long-term infected primary macrophages is due to an APO3G-independent mechanism.}, author = {Miyagi, Eri and Schwartzkopff, Franziska and Plishka, Ronald and Buckler-White, Alicia and Clouse, Kathleen A. and Strebel, Klaus}, citeulike-article-id = {3194335}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.virol.2008.06.033}, citeulike-linkout-1 = {http://www.sciencedirect.com/science/article/B6WXR-4T4HJC3-1/2/c7d6c39a98140f2d673415302f3ad03c}, day = {30}, doi = {10.1016/j.virol.2008.06.033}, journal = {Virology}, keywords = {apobec, hiv, macrophage}, month = {September}, number = {2}, pages = {266--274}, posted-at = {2008-09-04 16:45:26}, priority = {2}, title = {APOBEC3G-independent reduction in virion infectivity during long-term HIV-1 replication in terminally differentiated macrophages}, url = {http://dx.doi.org/10.1016/j.virol.2008.06.033}, volume = {379}, year = {2008} }

TY - JOUR ID - citeulike:3194335 L3 - citeulike-article-id:3194335 N2 - APOBEC3G (APO3G) is a cellular cytidine deaminase with potent antiviral activity. In the case of HIV, the antiviral activity of APO3G is counteracted by the viral Vif protein. Monocyte-derived macrophages (MDM) are terminally differentiated, non-dividing cells susceptible to HIV infection. Human MDM are known to express APO3G and HIV replication in these cells is dependent on Vif. Here we analyzed the correlation between HIV-1 replication and APO3G expression in MDM. Replication of wild type HIV-1 induced a gradual 4-5-fold reduction in APO3G expression. The efficiency of APO3G downregulation correlated with the efficiency of virus replication. Interestingly, despite downregulation of APO3G, the relative infectivity of viruses rapidly declined during the course of infection and was already reduced ~ 90% prior to peak virus production. Cell-free virus preparations showed increased levels of a 41 kDa MA-CA processing intermediate. Sequence analysis around the MA-CA cleavage site and the protease and LTR regions did not reveal deaminase-induced hypermutation of the viral genome, suggesting that APO3G activity is not responsible for the incomplete Gag processing. Thus, the loss of infectivity of HIV-1 viruses produced from long-term infected primary macrophages is due to an APO3G-independent mechanism. IS - 2 JF - Virology EP - 274 TI - APOBEC3G-independent reduction in virion infectivity during long-term HIV-1 replication in terminally differentiated macrophages VL - 379 SP - 266 KW - apobec KW - hiv KW - macrophage AU - Miyagi, Eri AU - Schwartzkopff, Franziska AU - Plishka, Ronald AU - Buckler-White, Alicia AU - Clouse, Kathleen AU - Strebel, Klaus PY - 2008/09/30/ UR - http://dx.doi.org/10.1016/j.virol.2008.06.033 ER -