title: A 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 confers protections against HIV-1 infection.
abstract: We investigated whether a 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 (T-cell immunoglobulin and mucin domain 1), modulates susceptibility to HIV-1 infection. The polymorphism was genotyped in three case/control cohorts of HIV-1 exposed seronegative individuals (HESN) and HIV-1 infected subjects from Italy, Peru, and Colombia; data from a Thai population were retrieved from the literature. Across all cohorts, homozygosity for the short TIM-1 allele was more common in HESNs than in HIV-1 infected subjects. A meta-analysis of the four association analyses yielded a p value of 0.005. In vitro infection assays of CD4+ T lymphocytes indicated that homozygosity for the short allele is associated with lower rate of HIV-1 replication. These results suggest that the deletion allele protects from HIV-1 infection with a recessive effect.
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, 20157, Milan, Italy. Electronic address: mara.biasin@unimi.it.
authors.forename: Mara
authors.initials: M
authors.lastname: Biasin
authors.affiliation: Scientific Institute IRCCS E. MEDEA, Bioinformatics, Bosisio Parini, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Sironi
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, 20157, Milan, Italy.
authors.forename: Irma
authors.initials: I
authors.lastname: Saulle
authors.affiliation: Scientific Institute IRCCS E. MEDEA, Bioinformatics, Bosisio Parini, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pontremoli
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, 20157, Milan, Italy.
authors.forename: Micaela
authors.initials: M
authors.lastname: Garziano
authors.affiliation: Scientific Institute IRCCS E. MEDEA, Bioinformatics, Bosisio Parini, Italy.
authors.forename: Rachele
authors.initials: R
authors.lastname: Cagliani
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, 20157, Milan, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Trabattoni
authors.affiliation: S. Maria Annunziata Hospital, 50122, Florence, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lo Caputo
authors.affiliation: S. Maria Annunziata Hospital, 50122, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vichi
authors.affiliation: S. Maria Annunziata Hospital, 50122, Florence, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mazzotta
authors.affiliation: Scientific Institute IRCCS E. MEDEA, Bioinformatics, Bosisio Parini, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Forni
authors.affiliation: Scientific Institute IRCCS E. MEDEA, Bioinformatics, Bosisio Parini, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Riva
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia.
authors.forename: Wbeimar
authors.initials: W
authors.lastname: Aguilar-Jimenez
authors.affiliation: AIDS Research Institute-IrsiCaixa-HIVACAT, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain; University of Vic and Central Catalonia, Vic, Spain.
authors.forename: Samandhy
authors.initials: S
authors.lastname: Cedeño
authors.affiliation: Asociación Civil Impacta Salud y Educación, Lima, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sanchez
authors.affiliation: AIDS Research Institute-IrsiCaixa-HIVACAT, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain; University of Vic and Central Catalonia, Vic, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia; Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia.
authors.forename: Wildeman
authors.initials: W
authors.lastname: Zapata
authors.affiliation: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Rugeles
authors.affiliation: Don C. Gnocchi Foundation ONLUS, IRCCS, 20148, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000235:genetics*; D016022:Case-Control Studies; D002478:Cells, Cultured; D015331:Cohort Studies; D003105:Colombia; D060467:Disease Resistance; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D010568:Peru; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D013785:Thailand; D014779:Virus Replication; D055815:Young Adult
chemical_list: D000596:Amino Acids; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1
keywords: HESN; HIV; Polymorphism; Resistance to infection; TIM-1