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.
A regulatory polymorphism in HAVCR2 modulates susceptibility to HIV-1 infection / M. Sironi, M. Biasin, F. Gnudi, R. Cagliani, I. Saulle, D. Forni, V. Rainone, D. Trabattoni, M. Garziano, F. Mazzotta, L. Real, A. Rivero-Juarez, A. Caruz, S. Lo Caputo, M. Clerici. - In: PLOS ONE. - ISSN 1932-6203. - 9:9(2014 Sep 02), pp. e106442.1-e106442.6.
|Titolo:||A regulatory polymorphism in HAVCR2 modulates susceptibility to HIV-1 infection|
SIRONI, MANUELA (Primo)
BIASIN, MARA (Secondo)
CLERICI, MARIO SALVATORE (Corresponding)
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Data di pubblicazione:||2-set-2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0106442|
|Appare nelle tipologie:||01 - Articolo su periodico|