A Knockout <i>IFNL4</i> Variant Is Associated With Protection From Sexually Transmitted HIV-1 Infection

Jaimes-Bernal, Claudia Patricia; Rallón, Norma; Benito, José M.; Omar, Mohamed; Gómez-Vidal, María Amparo; Márquez, Francisco J.; Sánchez-Arcas, Beatriz; Trujillo, Monte; Royo, José Luís; Saulle, Irma; Biasin, Mara; Rivero‐Juárez, Antonio; Caruz, Antonio

doi:10.1093/infdis/jiy584

Cited by 6 publications

(7 citation statements)

References 14 publications

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“…Sociodemographic and clinical variables of the subjects were previously described [45][46][47][48][49][50][51]. Two individuals in the HESN group were homozygous for CCR5 ∆32 and were excluded from subsequent analysis.…”

Section: Resultsmentioning

confidence: 99%

CD46 Genetic Variability and HIV-1 Infection Susceptibility

Serrano-Rísquez

Omar

Gómez-Vidal

et al. 2021

Cells

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CD46 is the main receptor for complement protein C3 and plays an important role in adaptive immune responses. CD46 genetic variants are associated with susceptibility to several infectious and autoimmune diseases. Additionally, CD46 function can be subverted by HIV-1 to evade attack by complement, a strategy shared by viruses of other families. We sought to determine the association between CD46 gene variants and HIV-1 acquired through intravenous drug use (IDU) and sexual routes (n = 823). Study subjects were of European ancestry and were HIV-1 infected (n = 438) or exposed but seronegative (n = 387). Genotyping of the rs2796265 SNP located in the CD46 gene region was done by allele-specific real-time PCR. A meta-analysis merging IDU and sexual cohorts indicates that the minor genotype (CC) was associated with increased resistance to HIV-1 infection OR = 0.2, 95% CI (0.07–0.61), p = 0.004. The HIV-1-protective genotype is correlated with reduced CD46 expression and alterations in the ratio of CD46 mRNA splicing isoforms.

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Section: Resultsmentioning

confidence: 99%

CD46 Genetic Variability and HIV-1 Infection Susceptibility

Serrano-Rísquez

Omar

Gómez-Vidal

et al. 2021

Cells

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“…Human populations outside of Africa show a clear positive evolutionary selection for a null IFNL4 gene, and the biological basis for such selection is not established. The most plausible hypothesis is that ancient populations outside of Africa have been devastated by epidemics of pathogens that benefit from IFNL4-dependent signaling or aggravate the disease course due to lower inflammatory response mediated by IFNL4, thus driving a positive selection for IFNL4 null allele carriers [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

IFNL4 genotype influences the rate of HIV-1 seroconversion in men who have sex with men

et al. 2022

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“…The role of these polymorphisms in the susceptibility/progression of HIV-infection has been investigated; results are interesting but controversial [54][55][56][57][58][59]. One of the earlier reports verified the association of rs12979860 in relation to both progression and protection from HIV-infection.…”

Section: Interferon Lambda Genetic Variantsmentioning

confidence: 99%

“…Prompt antiviral release of IFN-λ4 might thus be useful for infections needing an extremely fast, although transitory, immune response, but it is a hazard in infections requiring a more protracted defence such as HCV or HIV. Notably, these studies showed a recessive model of inheritance for the minor alleles in the case of parenteral transmission[58], but a dominant model in the case of sexual transmission and HCV-infection[51,59,66,67]. These discrepancies further underline the need to replicate such researches on larger cohorts with different exposure route as different HIV-1 infection risk could correlate with the need of different IFNL4 levels.In summary, it is evident that IFNL SNPs control HIV infection and replication, regardless of transmission route.…”

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confidence: 99%

Genetic and epigenetic regulation of natural resistance to HIV-1 infection: new approaches to unveil the HESN secret

Fenizia

Saulle

Clerici

et al. 2020

Expert Review of Clinical Immunology

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Since the identification of HIV, several studies reported the unusual case of small groups of subjects showing natural resistance to HIV-infection. These subjects are referred to as HIV-1-exposed seronegative (HESN) individuals and include people located in different regions of the world, with diverse ethnic backgrounds and routes of exposure. The mechanism/s responsible for protection from infection in HESN individuals are basically indefinite and most likely are multifactorial. Areas coveredHost factors, including genetic background as well as natural and acquired immunity have all been associated to this phenomenon. Recently, epigenetic factors have been investigated as possible determinants of reduced susceptibility to HIV-infection. With the advent of the OMICS era, the availability of techniques such as GWAS, RNAseq, and exome-sequencing in both bulk cell populations and single cells will likely lead to great strides in the understanding of the HESN mystery. Expert opinionThe employment of increasingly sophisticated techniques is allowing the gathering of an enormous amount of new data. The integration of such information will provide important hints that could lead to the identification of viral and host correlates of protection against HIV

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A Knockout IFNL4 Variant Is Associated With Protection From Sexually Transmitted HIV-1 Infection

Cited by 6 publications

References 14 publications

CD46 Genetic Variability and HIV-1 Infection Susceptibility

CD46 Genetic Variability and HIV-1 Infection Susceptibility

IFNL4 genotype influences the rate of HIV-1 seroconversion in men who have sex with men

Genetic and epigenetic regulation of natural resistance to HIV-1 infection: new approaches to unveil the HESN secret

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