The interplay between host genetic variation, viral replication and microbial translocation in untreated HIV-infected individuals.

Perkins, Molly R; Bartha, Istvan; Timmer, J Katherina; Liebner, Julia C; Wollinsky, David; Günthard, Huldrych F; Hauser, Christoph; Bernasconi, Enos; Hoffmann, Matthias; Calmy, Alexandra; Battegay, Manuel; Telenti, Amalio; Douek, Daniel C; Fellay, Jacques (2015). The interplay between host genetic variation, viral replication and microbial translocation in untreated HIV-infected individuals. Journal of infectious diseases, 212(4), pp. 578-584. Oxford University Press 10.1093/infdis/jiv089

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Systemic immune activation, a major determinant of 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. While human genetic variants influencing HIV viral load have been identified, it is unknown to what extent the host genetic background contributes to inter-individual differences in other determinants of HIV pathogenesis like 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 sCD14 (sCD14), a marker of LPS bioactivity and microbial translocation. We also assessed the correlations between HIV viral load, sCD14 and I-FABP. While we found no genome-wide significant determinant of the tested plasma markers, we observed strong associations between sCD14 and both HIV viral load and I-FABP, shedding new light on the relationships between processes that drive progression of untreated HIV infection.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Hauser, Christoph

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0022-1899

Publisher:

Oxford University Press

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

10 Apr 2015 15:23

Last Modified:

25 Oct 2019 01:33

Publisher DOI:

10.1093/infdis/jiv089

PubMed ID:

25701868

BORIS DOI:

10.7892/boris.64449

URI:

https://boris.unibe.ch/id/eprint/64449

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