Evasion from CypA- and APOBEC-mediated restrictions is insufficient for HIV-1 to efficiently grow in simian cells. Export

@article{citeulike:3782062, abstract = {We have recently generated a monkey cell-tropic virus termed NL-DT5R from an HIV-1 NL4-3 clone and demonstrated that both cyclophilin A (CypA)-binding loop in Gag-capsid (CA) and Vif are responsible for the species-restriction of HIV-1. In this study, we constructed 16 CypA-binding loop mutants from the HIV-1-derivative NL-DT5R, and analyzed them biologically and biochemically. The mutants displayed various multi-cycle infection potencies in cynomolgus monkey (CyM) HSC-F cells, but none of them grew significantly better than NL-DT5R. Consistently, any of the HIV-1 variants examined here did not effectively counter CyM TRIM5alpha as judged by single-cycle infectivity assays. Assessment of their single-cycle infectivity in simian and CyM TRIM5alpha-expressing feline cells in the presence of cyclosporin A (CsA) showed that intervention of CypA-CA interaction did not restore full NL-DT5R infectivity, while CsA increased infectivity of DT5R/4-3 carrying the sequence of NL4-3 CypA-binding loop up to the NL-DT5R level. Almost similar data were obtained in the experiments utilizing CypA-targeting siRNA. Together with our previous results regarding NL-DT5R, these data suggested that evasion from CypA- and APOBEC-mediated restrictions is still insufficient for HIV-1 to completely overcome the species barrier.}, author = {Kamada, Kazuya and Yamashita, Tomoki and Hatcho, Kazuki and Adachi, Akio and Nomaguchi, Masako}, citeulike-article-id = {3782062}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.micinf.2008.11.002}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19056509}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19056509}, day = {19}, doi = {10.1016/j.micinf.2008.11.002}, issn = {1286-4579}, journal = {Microbes and infection / Institut Pasteur}, keywords = {apobec, cyclophilins, trim}, month = {November}, posted-at = {2008-12-12 14:42:04}, priority = {2}, title = {Evasion from CypA- and APOBEC-mediated restrictions is insufficient for HIV-1 to efficiently grow in simian cells.}, url = {http://dx.doi.org/10.1016/j.micinf.2008.11.002}, year = {2008} }

TY - JOUR ID - citeulike:3782062 L3 - citeulike-article-id:3782062 N2 - We have recently generated a monkey cell-tropic virus termed NL-DT5R from an HIV-1 NL4-3 clone and demonstrated that both cyclophilin A (CypA)-binding loop in Gag-capsid (CA) and Vif are responsible for the species-restriction of HIV-1. In this study, we constructed 16 CypA-binding loop mutants from the HIV-1-derivative NL-DT5R, and analyzed them biologically and biochemically. The mutants displayed various multi-cycle infection potencies in cynomolgus monkey (CyM) HSC-F cells, but none of them grew significantly better than NL-DT5R. Consistently, any of the HIV-1 variants examined here did not effectively counter CyM TRIM5alpha as judged by single-cycle infectivity assays. Assessment of their single-cycle infectivity in simian and CyM TRIM5alpha-expressing feline cells in the presence of cyclosporin A (CsA) showed that intervention of CypA-CA interaction did not restore full NL-DT5R infectivity, while CsA increased infectivity of DT5R/4-3 carrying the sequence of NL4-3 CypA-binding loop up to the NL-DT5R level. Almost similar data were obtained in the experiments utilizing CypA-targeting siRNA. Together with our previous results regarding NL-DT5R, these data suggested that evasion from CypA- and APOBEC-mediated restrictions is still insufficient for HIV-1 to completely overcome the species barrier. JF - Microbes and infection / Institut Pasteur SN - 1286-4579 TI - Evasion from CypA- and APOBEC-mediated restrictions is insufficient for HIV-1 to efficiently grow in simian cells. KW - apobec KW - cyclophilins KW - trim AU - Kamada, Kazuya AU - Yamashita, Tomoki AU - Hatcho, Kazuki AU - Adachi, Akio AU - Nomaguchi, Masako PY - 2008/11/19/ UR - http://dx.doi.org/10.1016/j.micinf.2008.11.002 ER -