the antiviral spectra of trim5α orthologues and human trim family proteins against lentiviral production的抗病毒谱trim5αorthologues和人类削减家庭对慢病毒蛋白质产量.pdfVIP

The Antiviral Spectra of TRIM5a Orthologues and Human TRIM Family Proteins against Lentiviral Production 1 1¤ 1 1 2 Seiga Ohmine , Ryuta Sakuma , Toshie Sakuma , Tayaramma Thatava , Hiroaki Takeuchi , Yasuhiro Ikeda1* 1 Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, United States of America, 2 International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan Abstract Background: Rhesus monkey TRIM5a (TRIM5arh) recognizes the incoming HIV-1 core through its C-terminal B30.2(PRYSPRY) domain and promotes its premature disassembly or degradation before reverse transcription. Previously, we have shown that TRIM5arh blocks HIV-1 production through the N-terminal RBCC domain by the recognition of Gag polyproteins. Although all TRIM family proteins have RBCC domains, it remains elusive whether they possess similar late-restriction activities. Methodology/Principal Findings: We examined the antiviral spectra of TRIM5a orthologues and human TRIM family members which have a genetic locus proximal to human TRIM5a (TRIM5ahu), against primate lentiviral production. When HIV- 1 virus-like particles (VLPs) were generated in the presence of TRIM5a proteins, rhesus, African green and cynomolgus monkey TRIM5a (TRIM5aag and TRIM5acy), but not TRIM5ahu, were efficiently incorporated into VLPs, suggesting an interaction between HIV-1 Gag and TRIM5a proteins. TRIM5arh potently restricted the viral production of HIV-1 groups M and O and HIV- 2, but not simian lentiviruses including SIVMAC1A11, SIVAGMTan-1 or SIVAGMSAB-1. TRIM5ahu did not show notable late restriction activities against these lentiviruses. TRIM5aag and