HIV-1 infection is not a genetic disease; nevertheless, genetic factors could influence its susceptibility and progression. First evidence of this assumption dates back to 1996, when a homozygous variant for CCR5 chemokine receptor, Δ32, has been described showing a strong association with HIV-1 sexually transmission (1). Indeed, different phenotypes associated with non-classical outcomes to HIV-1 exposure and infection have been observed, leading to the development of the "immunological advantage" concept; a condition where the genetic background allows to control HIV-1 infection/replication in fortunate patients (2, 3). Some of the genes so far associated to this peculiar state include the ones briefly described hereafter. Endoplasmic Reticulum Associated Aminopeptidase type 2 (ERAP2) plays a key role in antigen presentation mechanisms. Trimming the N-terminal region of peptides ERAP2 adjusts the final peptide length for optimal binding to HLA class I molecules and modulates specific CTL responses (4). Haplotype-specific alternative splicing of ERAP2 gene results in either full-length (FL, hapA) or alternatively spliced (AS, haplotype B) mRNA; HapA is observed to be higher in HIV-Exposed Sero-Negative (HESN) individuals suggesting its involvement in conferring natural resistance to HIV-infection (5, 6). APOBEC3H, part of the APOBEC3 family, controls HIV-1 resistance at different levels (7). HAPI APOBEC3H haplotype is associated with sexually protection in HIV-1 transmission (7). Myxovirus resistance 2 (MX2) interferes with the viral replication decreasing nuclear viral DNA accumulation and integration (8). The G allele of rs2074560 in MX2 gene reveals protection from HIV-1 infection regardless of the transmission route (9). Regarding Toll-like receptor 3 (TLR3), in two HESN cohorts, a higher frequency of rs3775291 SNP (Leu412Phe) was observed suggesting protection against HIV-1 infection (10). Taking in mind that none of 5 the above-mentioned polymorphisms provides an absolute protection over HIV-1 infection, we decided to verify if these genetic variants - individually or in combination- might modulate the initial immunological and virological responses to antiretroviral therapy (ART).
Evaluation of the effect of protective genetic variants on cART success in HIV-1-infected patients.
G. NunnariMembro del Collaboration Group
;GF. Pellicanò.Membro del Collaboration Group
2020-01-01
Abstract
HIV-1 infection is not a genetic disease; nevertheless, genetic factors could influence its susceptibility and progression. First evidence of this assumption dates back to 1996, when a homozygous variant for CCR5 chemokine receptor, Δ32, has been described showing a strong association with HIV-1 sexually transmission (1). Indeed, different phenotypes associated with non-classical outcomes to HIV-1 exposure and infection have been observed, leading to the development of the "immunological advantage" concept; a condition where the genetic background allows to control HIV-1 infection/replication in fortunate patients (2, 3). Some of the genes so far associated to this peculiar state include the ones briefly described hereafter. Endoplasmic Reticulum Associated Aminopeptidase type 2 (ERAP2) plays a key role in antigen presentation mechanisms. Trimming the N-terminal region of peptides ERAP2 adjusts the final peptide length for optimal binding to HLA class I molecules and modulates specific CTL responses (4). Haplotype-specific alternative splicing of ERAP2 gene results in either full-length (FL, hapA) or alternatively spliced (AS, haplotype B) mRNA; HapA is observed to be higher in HIV-Exposed Sero-Negative (HESN) individuals suggesting its involvement in conferring natural resistance to HIV-infection (5, 6). APOBEC3H, part of the APOBEC3 family, controls HIV-1 resistance at different levels (7). HAPI APOBEC3H haplotype is associated with sexually protection in HIV-1 transmission (7). Myxovirus resistance 2 (MX2) interferes with the viral replication decreasing nuclear viral DNA accumulation and integration (8). The G allele of rs2074560 in MX2 gene reveals protection from HIV-1 infection regardless of the transmission route (9). Regarding Toll-like receptor 3 (TLR3), in two HESN cohorts, a higher frequency of rs3775291 SNP (Leu412Phe) was observed suggesting protection against HIV-1 infection (10). Taking in mind that none of 5 the above-mentioned polymorphisms provides an absolute protection over HIV-1 infection, we decided to verify if these genetic variants - individually or in combination- might modulate the initial immunological and virological responses to antiretroviral therapy (ART).Pubblicazioni consigliate
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