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 39 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 6.861024. 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 39 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.
| Original language | English |
|---|---|
| Article number | e106442 |
| Journal | PLoS One |
| Volume | 9 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2014 |
Fingerprint
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
A regulatory polymorphism in HAVCR2 modulates susceptibility to HIV-1 infection. / Sironi, Manuela; Biasin, Mara; Gnudi, Federica; Cagliani, Rachele; Saulle, Irma; Forni, Diego; Rainone, Veronica; Trabattoni, Daria; Garziano, Micaela; Mazzotta, Francesco; Real, Luis Miguel; Rivero-Juarez, Antonio; Caruz, Antonio; Caputo, Sergio Lo; Clerici, Mario.
In: PLoS One, Vol. 9, No. 9, e106442, 2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A regulatory polymorphism in HAVCR2 modulates susceptibility to HIV-1 infection
AU - Sironi, Manuela
AU - Biasin, Mara
AU - Gnudi, Federica
AU - Cagliani, Rachele
AU - Saulle, Irma
AU - Forni, Diego
AU - Rainone, Veronica
AU - Trabattoni, Daria
AU - Garziano, Micaela
AU - Mazzotta, Francesco
AU - Real, Luis Miguel
AU - Rivero-Juarez, Antonio
AU - Caruz, Antonio
AU - Caputo, Sergio Lo
AU - Clerici, Mario
PY - 2014
Y1 - 2014
N2 - 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 39 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 6.861024. 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 39 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.
AB - 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 39 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 6.861024. 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 39 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.
UR - http://www.scopus.com/inward/record.url?scp=84925849781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925849781&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0106442
DO - 10.1371/journal.pone.0106442
M3 - Article
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 9
M1 - e106442
ER -