Disentangling human tolerance and resistance against HIV.

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Version: author
Serval ID
serval:BIB_7B977B8D6294
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Disentangling human tolerance and resistance against HIV.
Journal
Plos Biology
Author(s)
Regoes R.R., McLaren P.J., Battegay M., Bernasconi E., Calmy A., Günthard H.F., Hoffmann M., Rauch A., Telenti A., Fellay J.
Working group(s)
Swiss HIV Cohort Study
Contributor(s)
Aubert V., Barth J., Battegay M., Bernasconi E., Böni J., Bucher HC., Burton-Jeangros C., Calmy A., Cavassini M., Egger M., Elzi L., Fehr J., Fellay J., Furrer H., Fux CA., Gorgievski M., Günthard H., Haerry D., Hasse B., Hirsch HH., Hösli I., Kahlert C., Kaiser L., Keiser O., Klimkait T., Kouyos R., Kovari H., Ledergerber B., Martinetti G., Martinez de Tejada B., Metzner K., Müller N., Nadal D., Pantaleo G., Rauch A., Regenass S., Rickenbach M., Rudin C., Schöni-Affolter F., Schmid P., Schultze D., Schüpbach J., Speck R., Staehelin C., Tarr P., Telenti A., Trkola A., Vernazza P., Weber R., Yerly S.
ISSN
1545-7885 (Electronic)
ISSN-L
1544-9173
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
12
Number
9
Pages
e1001951
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Abstract
In ecology, "disease tolerance" is defined as an evolutionary strategy of hosts against pathogens, characterized by reduced or absent pathogenesis despite high pathogen load. To our knowledge, tolerance has to date not been quantified and disentangled from host resistance to disease in any clinically relevant human infection. Using data from the Swiss HIV Cohort Study, we investigated if there is variation in tolerance to HIV in humans and if this variation is associated with polymorphisms in the human genome. In particular, we tested for associations between tolerance and alleles of the Human Leukocyte Antigen (HLA) genes, the CC chemokine receptor 5 (CCR5), the age at which individuals were infected, and their sex. We found that HLA-B alleles associated with better HIV control do not confer tolerance. The slower disease progression associated with these alleles can be fully attributed to the extent of viral load reduction in carriers. However, we observed that tolerance significantly varies across HLA-B genotypes with a relative standard deviation of 34%. Furthermore, we found that HLA-B homozygotes are less tolerant than heterozygotes. Lastly, tolerance was observed to decrease with age, resulting in a 1.7-fold difference in disease progression between 20 and 60-y-old individuals with the same viral load. Thus, disease tolerance is a feature of infection with HIV, and the identification of the mechanisms involved may pave the way to a better understanding of pathogenesis.
Pubmed
Web of science
Open Access
Yes
Create date
06/11/2014 20:16
Last modification date
20/08/2019 15:37
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