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

BMC Infectious Diseases

Research Article

S. Sibeko¹  N. Garrett¹  K. Mlisana¹  A. Kharsany¹  L. Werner¹  Q. Abdool Karim²  S. S. Abdool Karim²  V. Naranbhai³  H. Hong⁴  R. Moodley⁵  W. H. Carr⁶  T. Ndung’u⁷  C. M. Gray⁸  D. de Assis Rosa⁹  M. Altfeld^1,10  D. Chopera^1,11  A. V. S. Hill^1,12 

[1] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa;Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa;Mailman School of Public Health, Columbia University, New York, USA;Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa;Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK;HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa;Division of Virology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa;HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa;City University of New York - Medgar Evers College, New York, USA;Ragon Institute of MGH, MIT and Harvard University, Boston, USA;HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa;Ragon Institute of MGH, MIT and Harvard University, Boston, USA;KwaZulu-Natal Research Institute for Tuberculosis and HIV, University of KwaZulu-Natal, Durban, South Africa;Max Planck Institute for Infection Biology, Chariteplatz, D-10117, Berlin, Germany;National Institute of Communicable Diseases, Sandringham, South Africa;University of Cape Town, Cape Town, South Africa;National Institute of Communicable Diseases, Sandringham, South Africa;University of the Witwatersrand, Johannesburg, South Africa;Ragon Institute of MGH, MIT and Harvard University, Boston, USA;Leibniz Institute for Experimental Virology, Heinrich Pette Institute, Hamburg, Germany;University of Cape Town, Cape Town, South Africa;Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK;

关键词: KIR;    HLA;    HIV;    Acquisition;    Viral control;    Disease progression;   

DOI  :  10.1186/s12879-016-1361-1

 received in 2015-08-13, accepted in 2016-01-18,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundKiller-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.MethodsTo 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.ResultsNeither KIR repertoires nor HLA alleles were associated with HIV acquisition. However, KIR haplotype BB was associated with lower viral loads (−0.44log10 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.ConclusionsAlthough 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.

【 授权许可】

CC BY   
© Naranbhai et al. 2016