Both forms of TRIM5 therefore use the same mechanism of avidity-driven capsid pattern recognition.<b>IMPORTANCE</b> Rhesus macaques and owl monkeys are highly resistant to HIV-1 infection due to the activity of TRIM5 restriction factors.
Our results indicate that CypA inhibits HIV-1 infection in Vero cells not by promoting TRIM5α binding to the capsid but by blocking nuclear import of the HIV-1 preintegration complex.
Furthermore, the mRNA of anti-HIV molecules Elafin, TRIM5, Cathelicidin, HAD-4 and RNase7, previously associated with natural resistance to HIV-1 infection, positively correlated with the mRNA expression of VDR in HESNs, suggesting the potential participation of VitD in natural resistance to HIV-1.
This protocol led to the characterization of a human TRIM5alpha variant containing a mutation at arginine 335 as conferring resistance to HIV-1 infection.
TRIM5 proteins mediate a potent block to the cross-species transmission of retroviruses, the most well known being the TRIM5alpha protein from rhesus macaques, which potently inhibits human immunodeficiency virus type 1 (HIV-1) infection.
We used a quantitative real-time polymerase chain reaction (PCR) assay to measure levels of TRIM5alphahu expression in peripheral blood mononuclear cells (PBMCs) obtained from a cohort of individuals at high risk for HIV-1 infection in Durban, South Africa.
We report, however, that rhesus macaque dendritic cells (DCs) lack TRIM5alpha-mediated restriction and are equally permissive to HIV-1 infection as human DCs.
In this study, we show that during rhesus macaque TRIM5alpha (rhTRIM5alpha)-mediated restriction of HIV-1 infection, cytoplasmic HIV-1 viral complexes can associate with concentrations of TRIM5alpha protein termed cytoplasmic bodies.
Thus, polymorphisms in the Trim5 gene may influence the clinical course of HIV-1 infection also underscoring the antiviral effect of Trim5alpha on HIV-1 in vivo.
The host factor alpha isoform of the tripartite motif 5 (TRIM5alpha) restricts human immunodeficiency virus type 1 (HIV-1) infection in certain non-human primate species.
This construct was transfected into HeLa-T4 or HeLa cells which were then infected with the HIV-1IIIB or HIV-GFP-VSVG pseudotyped virus, to examine the effects of the TRIM5-Cyclophilin A fusion protein on HIV-1 infection.
The expression of TRIM5 alleles incapable of restricting HIV-1 infection may contribute to the previously reported increased susceptibility of M. nemestrina to HIV-1 infection in vivo.
Recently, tripartite motif 5alpha (TRIM5alpha) was identified as a factor that confers resistance to HIV-1 infection in Old World monkey cells.Subsequently, Sawyer et al.
Tripartite motif-containing 5 isoform-alpha (TRIM5alpha) protein from rhesus monkey (TRIM5alpharh) restricts human immunodeficiency virus type 1 (HIV-1) infection at a postentry, preintegration stage in the viral life cycle, by recognizing the incoming capsid and promoting its premature disassembly.
Here we investigated the abilities of domains from TRIM proteins (TRIM6, TRIM34, and TRIM21) that do not restrict HIV-1 infection to substitute for the domains of rhesus monkey TRIM5alpha (TRIM5alpha(rh)).
In addition, we extended previous work on the in vitro susceptibility of purified donor CD4 T cells (n = 125) to HIV-1 infection, and on the susceptibility of HeLa cells that were stably transduced with the different TRIM5 variants.
Thus, polymorphism in human TRIM5 may influence susceptibility to HIV-1 infection, a possibility that merits additional evaluation in independent cohorts.