Đang chuẩn bị nút TẢI XUỐNG, xin hãy chờ
Tải xuống
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: A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5α. | Kuroishi et al. Retrovirology 2010 7 58 http www.retrovirology.eom content 7 1 58 gtr RETROVIROLOGY RESEARCH Open Access A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5a Ayumu Kuroishi 1 Katarzyna Bozek2 Tatsuo Shioda1 and Emi E Nakayama 1 Abstract Background Human immunodeficiency virus type 1 HIV-1 productively infects only humans and chimpanzees but not Old World monkeys such as rhesus and cynomolgus CM monkeys. To establish a monkey model of HIV-1 AIDS several HIV-1 derivatives have been constructed. We previously reported that efficient replication of HIV-1 in CM cells was achieved after we replaced the loop between a-helices 6 and 7 L6 7 of the capsid protein CA with that of SIVmac239 in addition to the loop between a-helices 4 and 5 L4 5 and vif. This virus NL-4 5S6 7SvifS was supposed to escape from host restriction factors cyclophilin A CM TRIM5a and APOBEC3G. However the replicative capability of NL-4 5S6 7SvifS in human cells was severely impaired. Results By long-term cultivation of human CEMss cells infected with NL-4 5S6 7SvifS we succeeded in rescuing the impaired replicative capability of the virus in human cells. Sequence analysis of the CA region of the adapted virus revealed a G-to-E substitution at the 116th position of the CA G116E . Introduction of this substitution into the molecular DNA clone of NL-4 5S6 7SvifS indeed improved the virus replicative capability in human cells. Although the G116E substitution occurred during long-term cultivation of human cells infected with NL-4 5S6 7SvifS the viruses with G116E unexpectedly became resistant to CM but not human TRIM5a-mediated restriction. The 3-D model showed that position 116 is located in the 6th helix near L4 5 and L6 7 and is apparently exposed to the protein surface. The amino acid substitution at the 116th position caused a change in the structure of the protein surface because of the replacement of G which .