Human leukocyte antigen (HLA)-C and its association with HIV-1 transmission in discordant couple and mother-to-child cohorts
Human leukocyte antigen (HLA) molecules play a key role in regulating the immune response towards infectious agents like human immunodeficiency virus type-1 (HIV-1). They have been shown to influence transmission as well as the progression of HIV-1 towards acquired immune deficiency syndrome (AIDS). Roles of HLA-A and HLA-B have been documented extensively; however, HLA-C has been poorly studied. In the present study, we have evaluated the role of HLA-C in discordant couple and mother-to-child cohorts. HLA-C*07 was higher both in HIV-1-infected spouses and infants as compared to exposed uninfected spouses and infants. However, this was not significant. HLA-C*15 was significantly higher in HIV-1-exposed uninfected babies as compared to infected babies. Lack of treatment in mothers and breastfeeding were significantly associated with HIV-1 transmission. HLA-C*07 may be a susceptible allele in HIV-1 transmission, whereas HLA-C*15 may be a protective allele in mother-to-child cohorts, independent of feeding options and treatment. These findings could be important in targeting immune responses via population-specific vaccine strategies against HIV-1.
KeywordsHuman leukocyte antigen HIV-1 transmission HLA-C Discordant couple cohort Mother-to-child cohort
We thank Ms. Shilpa Kerkar for her help in sample collection and the counselling staff at the collaborating hospital for their help in recruiting patients and their follow-up. NSB is supported by the University Grants Commission - Senior Research Fellowship (UGC-SRF).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Apps R, Qi Y, Carlson JM, Chen H, Gao X, Thomas R, Yuki Y, del Prete GQ, Goulder P, Brumme ZL, Brumme CJ, John M, Mallal S, Nelson G, Bosch R, Heckerman D, Stein JL, Soderberg KA, Moody MA, Denny TN, Zeng X, Fang J, Moffett A, Lifson JD, Goedert JJ, Buchbinder S, Kirk GD, Fellay J, McLaren P, Deeks SG, Pereyra F, Walker B, Michael NL, Weintrob A, Wolinsky S, Liao W, Carrington M (2013) Influence of HLA-C expression level on HIV control. Science 340:87–91. https://doi.org/10.1126/science.1232685 CrossRefPubMedPubMedCentralGoogle Scholar
- Farquhar C, Rowland-Jones S, Mbori-Ngacha D, Redman M, Lohman B, Slyker J, Otieno P, Obimbo E, Rostron T, Ochieng J, Oyugi J, Bosire R, John-Stewart G (2004) Human leukocyte antigen (HLA) B*18 and protection against mother-to-child HIV type 1 transmission. AIDS Res Hum Retrovir 20:692–697. https://doi.org/10.1089/0889222041524616 CrossRefPubMedGoogle Scholar
- Fellay J, Ge D, Shianna KV, Colombo S, Ledergerber B, Cirulli ET, Urban TJ, Zhang K, Gumbs CE, Smith JP, Castagna A, Cozzi-Lepri A, de Luca A, Easterbrook P, Günthard HF, Mallal S, Mussini C, Dalmau J, Martinez-Picado J, Miro JM, Obel N, Wolinsky SM, Martinson JJ, Detels R, Margolick JB, Jacobson LP, Descombes P, Antonarakis SE, Beckmann JS, O'Brien SJ, Letvin NL, McMichael AJ, Haynes BF, Carrington M, Feng S, Telenti A, Goldstein DB, NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI) (2009) Common genetic variation and the control of HIV-1 in humans. PLoS Genet 5:e1000791. https://doi.org/10.1371/journal.pgen.1000791 CrossRefPubMedPubMedCentralGoogle Scholar
- Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, Sayer D, Castley A, Mamotte C, Maxwell D, James I, Christiansen FT (2002) Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 359:727–732. https://doi.org/10.1016/S0140-6736(02)07873-X CrossRefPubMedGoogle Scholar
- National AIDS Control Organisation (2015) National Guidelines for HIV Testing. Available from: http://www.naco.gov.in/sites/default/files/National_Guidelines_for_HIV_Testing_21Apr2016.pdf
- Peterson TA, Kimani J, Wachihi C, Bielawny T, Mendoza L, Thavaneswaran S, Narayansingh MJ, Kariri T, Liang B, Ball TB, Ngugi EN, Plummer FA, Luo M (2013) HLA class I associations with rates of HIV-1 seroconversion and disease progression in the Pumwani Sex Worker Cohort. Tissue Antigens 81:93–107. https://doi.org/10.1111/tan.12051 CrossRefPubMedGoogle Scholar
- Trachtenberg E, Erlich H (2001) A review of the role of human leukocyte antigen (HLA) system as a host immunogenetic factor influencing HIV transmission and progression to AIDS. In: Korber BT, Brander C, Haynes BF (eds) HIV Molecular Immunology 2001. Theoretical Biology and Biophysics group, LANL, Los Alamos, pp I43–60Google Scholar