A Regulatory Polymorphism in HAVCR2 Modulates Susceptibility to HIV-1 Infection

Manuela Sironi, Mara Biasin, Federica Gnudi, Rachele Cagliani, Irma Saulle, Diego Forni, Veronica Rainone, Daria Trabattoni, Micaela Garziano, Francesco Mazzotta, Luis Miguel Real, Antonio Rivero-Juarez, Antonio Caruz, Sergio Lo Caputo and Mario Clerici

PLOS ONE, 2014, vol. 9, issue 9, 1-6

Abstract: The HAVCR2 gene encodes TIM-3, an immunoglobulin superfamily member expressed by exhausted CD8+ T cells during chronic viral infection. We investigated whether genetic variation at HAVCR2 modulates the susceptibility to HIV-1 acquisition; specifically we focused on a 3′ UTR variant (rs4704846, A/G) that represents a natural selection target. We genotyped rs4704846 in three independent cohorts of HIV-1 exposed seronegative (HESN) individuals with different geographic origin (Italy and Spain) and distinct route of exposure to HIV-1 (sexual and injection drug use). Matched HIV-1 positive subjects and healthy controls were also analyzed. In all case-control cohorts the minor G allele at rs4704846 was more common in HIV-1 infected individuals than in HESN, with healthy controls showing intermediate frequency. Results from the three association analyses were combined through a random effect meta-analysis, which revealed no heterogeneity among samples (Cochrane's Q, p value = 0.89, I2 = 0) and yielded a p value of 6.8 ×10−4. The minor G allele at rs4704846 was found to increase HAVCR2 expression after in vitro HIV-1 infection. Thus, a positively selected polymorphism in the 3′ UTR, which modulates HAVCR2 expression, is associated with the susceptibility to HIV-1 infection. These data warrant further investigation into the role of TIM-3 in the prevention and treatment of HIV-1/AIDS.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0106442

DOI: 10.1371/journal.pone.0106442

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