RT Conference Proceedings
T1 TRIM5-mediated retrovirus restriction is modulated by type I interferon.
A1 Ortega-Prieto, Ana María
A1 Boehmer, Nina
A1 Dinc, Hanife
A1 Betancor, Gilberto
A1 Petrosyan, Eduard
A1 Malim, Michael H.
A1 Jiménez-Guardeño, José Manuel
K1 Virología
K1 Interferón
AB Since the identification in 2004 of the interferon-stimulated gene (ISG) tripartite motif-containing protein 5 α(TRIM5α) from rhesus macaques as a restriction factor preventing HIV-1 infection in these monkeys, the antiretroviralactivity of several primate TRIM5α orthologs against HIV-1 has been described, establishing the model that TRIM5αinhibits retroviral infection in a species-specific manner, preventing host cell infection by retroviruses from differentspecies through fragmentation of incoming viral capsids and the activation of innate immune pathways. However, thelong held dogma that retroviruses have evolved to evade the TRIM5α ortholog present in species to which they areendemic has recently changed by the identification of human TRIM5α as a major determinant in the Type 1 IFNinduced suppression of HIV-1 replication, presumably contributing to the immune control of HIV-1 in infectedhumans.Given that IFN levels are elevated during natural retrovirus infection and that IFN treatment enables human TRIM5αrestriction of HIV-1, we evaluated the IFN-induced restriction of distinct retroviruses in presence of TRIM5αorthologues from different primate species. To this end, we ectopically expressed different TRIM5α orthologues inhuman U87 cells where endogenous TRIM5α and MX2 expression had been ablated using CRISPR–Cas9 genomeediting, and then challenged with a wide range of GFP-encoding retrovirus-based vectors in the presence or absenceof IFN. This approach reveals that IFN treatment changes the patterns of TRIM5α-mediated retrovirus restriction,suggesting that the role of TRIM5α in retrovirus infection should be re-examined under conditions that more closelymimic those encountered during natural virus infection.
YR 2024
FD 2024
LK https://hdl.handle.net/10630/32623
UL https://hdl.handle.net/10630/32623
LA eng
NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026