PMID- 30289808 OWN - NLM STAT- MEDLINE DCOM- 20191104 LR - 20191104 IS - 1473-5571 (Electronic) IS - 0269-9370 (Linking) VI - 32 IP - 18 DP - 2018 Nov 28 TI - Inhibitory natural killer cell receptor KIR3DL1 with its ligand Bw4 constraints HIV-1 disease among South Indians. PG - 2679-2688 LID - 10.1097/QAD.0000000000002028 [doi] AB - OBJECTIVE: To investigate the role of genotypic and phenotypic characteristics of killer cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) class-1 ligands in HIV-1 disease progression. STUDY DESIGN AND METHODS: This is a nested case-control study including 347 HIV seropositive (HIV-1+) individuals from South India constituting 45 long-term nonprogressors (LTNPs) and 302 disease progressors. KIR genotyping was performed by multiplex sequence-specific primer-directed PCR (SSP-PCR). Phenotypic expressions of KIR3DL1/S1 was studied using multiparametric flow cytometry assay. HLA-Bw4 and Bw6 epitopes were determined by ARMS-PCR. HLA-Bw4I80, HLA-Bw4T80, HLA-C1, HLA-C2, and HLA-Aw4 were genotyped using SSP-PCR. Serum levels of IFN-gamma was quantified using ELISA method. RESULTS: Overall, 37 different KIR genotypes were observed and the distribution of genotypes with AB-AB (OR = 2.2, P = 0.033) constellations showed significant increase among LTNPs. The frequencies of 3DL1-2DL3-2DL5 (OR = 2.2, Pc = 0.031), 3DL1-Bw4/Aw4 (OR = 2.49, Pc = 0.019), homozygous Bw4 (OR = 2.422, Pc = 0.011) were observed higher in LTNPs and 2DS1-2DS2-2DS3 (OR = 0.475, Pc = 0.03), homozygous Bw6 (OR = 0.413, Pc = 0.011) were higher in the disease progressors. Flow cytometry assay showed the increased expression and maintenance of 3DL1/S1+NK cells in LTNPs (P = 0.0001). Further the expansion of 3DS1+NK cells was higher than 3DL1+NK cells in the heterozygous 3DL1/S1 LTNPs (P = 0.001). CONCLUSION: The inhibitory receptor 3DL1 with Bw4 and its A-haplotype defining KIR genes (2DL3/L5) confers protection against HIV-1 disease progression. An increased expression and maintenance of 3DL1/S1+ natural killer cells may contribute to the efficient activation of the natural killer cells and subsequent long-term nonprogression (LTNPn) to the disease. FAU - Maruthamuthu, Stalinraja AU - Maruthamuthu S AD - Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai. FAU - Rajalingam, Raja AU - Rajalingam R AD - Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California, San Francisco, California, USA. FAU - Pandian, Kalaimani AU - Pandian K AD - Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai. FAU - Madasamy, Suresh AU - Madasamy S AD - ART Medical Centre. FAU - Manoharan, Mythreyee AU - Manoharan M AD - Department of Microbiology, Government Theni Medical College and Hospital, Theni, India. FAU - Pitchai, Leishman AU - Pitchai L AD - Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai. FAU - Murugesan, Amudhan AU - Murugesan A AD - Department of Microbiology, Government Theni Medical College and Hospital, Theni, India. FAU - Mariakuttikan, Jayalakshmi AU - Mariakuttikan J AD - Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai. LA - eng PT - Journal Article PL - England TA - AIDS JT - AIDS (London, England) JID - 8710219 RN - 0 (HLA-B Antigens) RN - 0 (KIR3DL1 protein, human) RN - 0 (Receptors, KIR3DL1) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adolescent MH - Adult MH - Case-Control Studies MH - Disease Progression MH - Disease Resistance MH - Female MH - *Genotype MH - HIV Infections/*genetics/*immunology/virology MH - HIV-1/*immunology MH - HLA-B Antigens/*genetics/metabolism MH - Humans MH - India MH - Interferon-gamma/blood MH - Male MH - Middle Aged MH - Prospective Studies MH - Receptors, KIR3DL1/*genetics/metabolism MH - Young Adult EDAT- 2018/10/06 06:00 MHDA- 2019/11/05 06:00 CRDT- 2018/10/06 06:00 PHST- 2018/10/06 06:00 [pubmed] PHST- 2019/11/05 06:00 [medline] PHST- 2018/10/06 06:00 [entrez] AID - 10.1097/QAD.0000000000002028 [doi] PST - ppublish SO - AIDS. 2018 Nov 28;32(18):2679-2688. doi: 10.1097/QAD.0000000000002028.