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, Mario Clerici

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 languageEnglish
Article numbere106442
JournalPLoS One
Volume9
Issue number9
DOIs
Publication statusPublished - 2014

Fingerprint

Human immunodeficiency virus 1
Polymorphism
HIV Infections
Untranslated Regions
HIV-1
genetic polymorphism
infection
T-cells
Immunoglobulins
Genes
Alleles
Pharmaceutical Preparations
drug injection
alleles
exposure pathways
Genetic Selection
Virus Diseases
meta-analysis
Spain
provenance

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 journalArticle

Sironi, M, Biasin, M, Gnudi, F, Cagliani, R, Saulle, I, Forni, D, Rainone, V, Trabattoni, D, Garziano, M, Mazzotta, F, Real, LM, Rivero-Juarez, A, Caruz, A, Caputo, SL & Clerici, M 2014, 'A regulatory polymorphism in HAVCR2 modulates susceptibility to HIV-1 infection', PLoS One, vol. 9, no. 9, e106442. https://doi.org/10.1371/journal.pone.0106442
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. / A regulatory polymorphism in HAVCR2 modulates susceptibility to HIV-1 infection. In: PLoS One. 2014 ; Vol. 9, No. 9.
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