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J Infect Dis. 2015 Aug 15;212(4):578-84. doi: 10.1093/infdis/jiv089. Epub 2015 Feb 20.

The Interplay Between Host Genetic Variation, Viral Replication, and Microbial Translocation in Untreated HIV-Infected Individuals.

Author information

1
Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland.
2
Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne Swiss Institute of Bioinformatics, Lausanne Institute of Microbiology, University Hospital and University of Lausanne.
3
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich and University of Zurich.
4
University Clinic of Infectious Diseases, University Hospital Bern and University of Bern.
5
Division of Infectious Diseases, Regional Hospital Lugano.
6
Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St Gallen.
7
HIV Unit, Department of Internal Medicine, Geneva University Hospital.
8
Division of Infectious Diseases and Hospital Epidemiology, Departments of Clinical and Biomedical Research, University Hospital Basel, University of Basel, Switzerland.
9
Institute of Microbiology, University Hospital and University of Lausanne.
10
Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne Swiss Institute of Bioinformatics, Lausanne.

Erratum in

Abstract

Systemic immune activation, a major determinant of human immunodeficiency virus (HIV) disease progression, is the result of a complex interplay between viral replication, dysregulation of the immune system, and microbial translocation due to gut mucosal damage. Although human genetic variants influencing HIV load have been identified, it is unknown how much the host genetic background contributes to interindividual differences in other determinants of HIV pathogenesis such as gut damage and microbial translocation. Using samples and data from 717 untreated participants in the Swiss HIV Cohort Study and a genome-wide association study design, we searched for human genetic determinants of plasma levels of intestinal fatty acid-binding protein (I-FABP/FABP2), a marker of gut damage, and of soluble CD14 (sCD14), a marker of lipopolysaccharide bioactivity and microbial translocation. We also assessed the correlations between HIV load, sCD14, and I-FABP. Although we found no genome-wide significant determinant of the tested plasma markers, we observed strong associations between sCD14 and both HIV load and I-FABP, shedding new light on the relationships between processes that drive progression of untreated HIV infection.

KEYWORDS:

HIV; I-FABP; genome-wide association study; host genomics; immune activation; microbial translocation; sCD14

PMID:
25701868
PMCID:
PMC4539895
DOI:
10.1093/infdis/jiv089
[Indexed for MEDLINE]
Free PMC Article

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