Abstract
BackgroundTripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against HIV. TRIM5α targets the HIV capsid for proteosomal destruction. Cyclophilin A, an intracellular protein has also been reported to influence HIV infectivity in a cell-specific manner. Accordingly, variations in TRIM5α and Cyclophilin A genes have been documented to influence HIV-1 disease progression. However, these variations have not been documented among Elite controllers in Uganda and whether they play a role in viral suppression remains largely undocumented. Our study focused on identifying the variations in TRIM5α and Cyclophilin A genes among HIV-1 Elite controllers and non-controllers in Uganda.ResultsFrom the sequence analysis, the rs10838525 G > A mutation in exon 2 of TRIM5α was only found among elite controllers (30%) while the rs3824949 in the 5′UTR was seen among 25% of the non-controllers. In the Cyclophilin A promoter, rs6850 was seen among 62.5% of the non-controllers and only among 10% elite controllers. Furthermore, rs17860048 in the Cyclophillin A promoter was predominantly seen among elite controllers (30%) and 12.5% non-controllers. From gene expression analysis, we noted that the respective genes were generally elevated among elite controllers, however, this difference was not statistically significant (TRIM5α p = 0.6095; Cyclophilin A p = 0.6389).ConclusionVariations in TRIM5α and Cyclophillin A promoter may influence HIV viral suppression. The rs10838525 SNP in TRIM5α may contribute to viral suppression among HIV-1 elite controllers. The rs6850 in the cyclophillin A gene may be responsible for HIV-1 rapid progression among HIV-1 non-controllers. These SNPs should be investigated mechanistically to determine their precise role in HIV-1 viral suppression.
Highlights
Tripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against Human immunodeficiency virus (HIV)
Tripartite Motif-containing 5α (TRIM5α) and Cyclophilin A gene variations Considerable evidence suggests that variations in genes of intrinsic cellular defense against HIV influence HIV-1 disease progression [13, 14]
Results indicate that rs10838525 single nucleotide polymorphisms (SNPs) were predominant among elite controllers (30%) while rs3824949 was more among non-controllers (25%) (Table 2; Fig. 1)
Summary
Tripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against HIV. Amanya et al Retrovirology (2020) 17:19 viral replication at distinct stages have been reported to influence HIV susceptibility and disease progression [3] These include; Tripartite Motif-containing 5α (TRIM5α), Apolipoprotein B messenger RNA editing enzyme catalytic polypeptide-like 3 (APOBEC3), Tetherin/bone marrow stromal cell antigen (BST2) [3], Myxovirus resistance protein 2 (MxB), and Sterile α motif domain-HD domaincontaining protein 1(SAMDH1) [4]. TRIM5α, a member of the tripartite motif-containing family of proteins restricts HIV by interfering with viral capsid uncoating terminating downstream processes that facilitate HIV genome integration [5] It is implicated in the modulation of innate immune signaling via nuclear factor kappaB (NF-kB) and activator protein 1 (AP-1) leading to the production of inflammatory cytokines such as interleukin-2 (IL-2) & interferon-gamma (IFN-γ), along with various cell surface markers [6]. Polymorphisms in CypA gene have been documented to influence susceptibility to HIV-1 infection [10]
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