TY - JOUR
T1 - The antiviral spectra of TRIM5α orthologues and human trim family proteins against lentiviral production
AU - Ohmine, Seiga
AU - Sakuma, Ryuta
AU - Sakuma, Toshie
AU - Thatava, Tayaramma
AU - Takeuch, Hiroaki
AU - Ikeda, Yasuhiro
PY - 2011
Y1 - 2011
N2 - Background: Rhesus monkey Trim5α (TRIM5αrh) 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 Trim5αrh 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 Trim5α orthologues and human TRIM family members which have a genetic locus proximal to human Trim5α (Trim5αhu), against primate lentiviral production. When HIV- 1 virus-like particles (VLPs) were generated in the presence of Trim5α proteins, rhesus, African green and cynomolgus monkey Trim5α (Trim5αag and Trim5αcy), but not Trim5αhu, were efficiently incorporated into VLPs, suggesting an interaction between HIV-1 Gag and Trim5α proteins. Trim5αrh 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. Trim5αhu did not show notable late restriction activities against these lentiviruses. Trim5αag and Trim5αcy showed intermediate restriction phenotypes against HIV-1 and HIV-2, but showed no restriction activity against SIV production. A series of chimeric Trim5α constructs indicated that the N-terminal region of Trim5αag and Trim5αcy are essential for the late restriction activity, while the C-terminal region of Trim5αcy negatively regulates the late restriction activity against HIV-1. When select human TRIM family proteins were examined, TRIM21 and 22 were efficiently incorporated into HIV-1 VLPs, while only TRIM22 reduced HIV-1 titers up to 5-fold. The antiviral activities and encapsidation efficiencies did not correlate with their relative expression levels in the producer cells. Conclusions/Significance: Our results demonstrated the variations in the late restriction activities among closely related Trim5α orthologues and a subset of human TRIM family proteins, providing further insights into the late restriction activities of TRIM proteins.
AB - Background: Rhesus monkey Trim5α (TRIM5αrh) 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 Trim5αrh 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 Trim5α orthologues and human TRIM family members which have a genetic locus proximal to human Trim5α (Trim5αhu), against primate lentiviral production. When HIV- 1 virus-like particles (VLPs) were generated in the presence of Trim5α proteins, rhesus, African green and cynomolgus monkey Trim5α (Trim5αag and Trim5αcy), but not Trim5αhu, were efficiently incorporated into VLPs, suggesting an interaction between HIV-1 Gag and Trim5α proteins. Trim5αrh 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. Trim5αhu did not show notable late restriction activities against these lentiviruses. Trim5αag and Trim5αcy showed intermediate restriction phenotypes against HIV-1 and HIV-2, but showed no restriction activity against SIV production. A series of chimeric Trim5α constructs indicated that the N-terminal region of Trim5αag and Trim5αcy are essential for the late restriction activity, while the C-terminal region of Trim5αcy negatively regulates the late restriction activity against HIV-1. When select human TRIM family proteins were examined, TRIM21 and 22 were efficiently incorporated into HIV-1 VLPs, while only TRIM22 reduced HIV-1 titers up to 5-fold. The antiviral activities and encapsidation efficiencies did not correlate with their relative expression levels in the producer cells. Conclusions/Significance: Our results demonstrated the variations in the late restriction activities among closely related Trim5α orthologues and a subset of human TRIM family proteins, providing further insights into the late restriction activities of TRIM proteins.
UR - http://www.scopus.com/inward/record.url?scp=79251548903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79251548903&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0016121
DO - 10.1371/journal.pone.0016121
M3 - Article
C2 - 21264255
AN - SCOPUS:79251548903
SN - 1932-6203
VL - 6
JO - PloS one
JF - PloS one
IS - 1
M1 - e16121
ER -