Genome-wide association study on the development of cross-reactive neutralizing antibodies in HIV-1 infected individuals

Zelda Euler; Marit J van Gils; Brigitte D Boeser-Nunnink; Hanneke Schuitemaker; Daniëlle van Manen

doi:10.1371/journal.pone.0054684

Genome-wide association study on the development of cross-reactive neutralizing antibodies in HIV-1 infected individuals

PLoS One. 2013;8(1):e54684. doi: 10.1371/journal.pone.0054684. Epub 2013 Jan 23.

Authors

Zelda Euler¹, Marit J van Gils, Brigitte D Boeser-Nunnink, Hanneke Schuitemaker, Daniëlle van Manen

Affiliation

¹ Department Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.

Abstract

Broadly neutralizing antibodies may protect against HIV-1 acquisition. In natural infection, only 10-30% of patients have cross-reactive neutralizing humoral immunity which may relate to viral and or host factors. To explore the role of host genetic markers in the formation of cross-reactive neutralizing activity (CrNA) in HIV-1 infected individuals, we performed a genome-wide association study (GWAS), in participants of the Amsterdam Cohort Studies with known CrNA in their sera. Single-nucleotide polymorphisms (SNPs) with the strongest P-values are located in the major histocompatibility complex (MHC) region, close to MICA (P = 7.68 × 10(-7)), HLA-B (P = 6.96 × 10(-6)) and in the coding region of HCP5 (P = 1.34 × 10(-5)). However, none of the signals reached genome-wide significance. Our findings underline the potential involvement of genes close or within the MHC region with the development of CrNA.

MeSH terms

Antibodies, Neutralizing / blood
Antibodies, Neutralizing / immunology*
CD4 Lymphocyte Count
Cluster Analysis
Cross Reactions / genetics*
Cross Reactions / immunology*
Genome-Wide Association Study
HIV Antibodies / blood
HIV Antibodies / immunology*
HIV Infections / genetics*
HIV Infections / immunology*
HIV Infections / virology
HIV-1 / immunology*
HLA Antigens / genetics
HLA Antigens / immunology
Homosexuality
Host-Pathogen Interactions / genetics
Host-Pathogen Interactions / immunology
Humans
Male
Polymorphism, Single Nucleotide
Viral Load

Substances

Antibodies, Neutralizing
HIV Antibodies
HLA Antigens

Grants and funding

This study was financially supported by The Netherlands Organization for Scientific Research (grant 918.66.628 and 912.06.046), the European Community’s Six Framework Program European HIV Enterprise (EUROPRISE; FP6/2007–2012) under grant agreement 037611 and the European Community’s Seventh Framework Program Next Generation HIV-1 Immunogens inducing broadly reactive Neutralizing antibodies (NGIN) (FP7/2007–2013) under grant agreement 201433. The ACS are financially supported by the Center for Infectious Disease Control of The Netherlands National Institute for Public Health and the Environment. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.