Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African women.

Autor: Naranbhai V; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. vivekn@well.ox.ac.uk.; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. vivekn@well.ox.ac.uk.; HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa. vivekn@well.ox.ac.uk., de Assis Rosa D; National Institute of Communicable Diseases, Sandringham, South Africa. debradeassisrosa@gmail.com.; University of the Witwatersrand, Johannesburg, South Africa. debradeassisrosa@gmail.com., Werner L; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. liesiew@gmail.com., Moodley R; HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa. ramony111@gmail.com., Hong H; Division of Virology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. heatherh@nicd.ac.za., Kharsany A; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. KHARSANY@ukzn.ac.za., Mlisana K; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. mlisanak@gmail.com., Sibeko S; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. singeziwe@yahoo.com., Garrett N; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. Nigel.Garrett@caprisa.org., Chopera D; University of Cape Town, Cape Town, South Africa. denis.chopera@gmail.com., Carr WH; HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa. wcarr@mec.cuny.edu.; City University of New York - Medgar Evers College, New York, USA. wcarr@mec.cuny.edu.; Ragon Institute of MGH, MIT and Harvard University, Boston, USA. wcarr@mec.cuny.edu., Abdool Karim Q; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. Quarraisha.AbdoolKarim@caprisa.org.; Mailman School of Public Health, Columbia University, New York, USA. Quarraisha.AbdoolKarim@caprisa.org., Hill AV; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. adrian.hill@ndm.ox.ac.uk., Abdool Karim SS; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. Salim.AbdoolKarim@caprisa.org.; Mailman School of Public Health, Columbia University, New York, USA. Salim.AbdoolKarim@caprisa.org., Altfeld M; Ragon Institute of MGH, MIT and Harvard University, Boston, USA. marcus.altfeld@hpi.uni-hamburg.de.; Leibniz Institute for Experimental Virology, Heinrich Pette Institute, Hamburg, Germany. marcus.altfeld@hpi.uni-hamburg.de., Gray CM; National Institute of Communicable Diseases, Sandringham, South Africa. clive.gray@uct.ac.za.; University of Cape Town, Cape Town, South Africa. clive.gray@uct.ac.za., Ndung'u T; HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa. ndungu@ukzn.ac.za.; Ragon Institute of MGH, MIT and Harvard University, Boston, USA. ndungu@ukzn.ac.za.; KwaZulu-Natal Research Institute for Tuberculosis and HIV, University of KwaZulu-Natal, Durban, South Africa. ndungu@ukzn.ac.za.; Max Planck Institute for Infection Biology, Chariteplatz, D-10117, Berlin, Germany. ndungu@ukzn.ac.za.
Jazyk: angličtina
Zdroj: BMC infectious diseases [BMC Infect Dis] 2016 Jan 25; Vol. 16, pp. 27. Date of Electronic Publication: 2016 Jan 25.
DOI: 10.1186/s12879-016-1361-1
Abstrakt: Background: Killer-cell Immunoglobulin-like Receptors (KIR) interact with Human Leukocyte Antigen (HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies.
Methods: To assess the role of KIR and KIR ligands in HIV acquisition and disease course, we studied at-risk women in South Africa between 2004-2010. Logistic regression was used for nested case-control analysis of 154 women who acquired vs. 155 who did not acquire HIV, despite high exposure. Linear mixed-effects models were used for cohort analysis of 139 women followed prospectively for a median of 54 months (IQR 31-69) until 2014.
Results: Neither KIR repertoires nor HLA alleles were associated with HIV acquisition. However, KIR haplotype BB was associated with lower viral loads (-0.44 log10 copies/ml; SE = 0.18; p = 0.03) and higher CD4+ T-cell counts (+80 cells/μl; SE = 42; p = 0.04). This was largely explained by the protective effect of KIR2DL2/KIR2DS2 on the B haplotype and reciprocal detrimental effect of KIR2DL3 on the A haplotype.
Conclusions: Although neither KIR nor HLA appear to have a role in HIV acquisition, our data are consistent with involvement of KIR2DL2 in HIV control. Additional studies to replicate these findings are indicated.
Databáze: MEDLINE
Externí odkaz: