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Disentangling human tolerance and resistance against HIV.

  • Regoes RR Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland.
  • McLaren PJ Global Health Institute, EPF Lausanne, Lausanne, Switzerland; Institute of Microbiology, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Battegay M Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Bernasconi E Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
  • Calmy A Geneva University Hospital, HIV Unit, Department of Internal Medicine, Geneva, Switzerland.
  • Günthard HF Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Hoffmann M Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St.Gallen, St.Gallen, Switzerland.
  • Rauch A University Clinic of Infectious Diseases, University Hospital Bern and University of Bern, Bern, Switzerland.
  • Telenti A Institute of Microbiology, University of Lausanne, Lausanne, Switzerland.
  • Fellay J Global Health Institute, EPF Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
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  • 2014-09-17
Published in:
  • PLoS biology. - 2014
Adult
Age Factors
Alleles
CD4 Lymphocyte Count
Cohort Studies
Disease Progression
Female
Gene Frequency
Genome, Human
HIV Infections
HIV-1
HLA-B Antigens
Heterozygote
Homozygote
Host-Pathogen Interactions
Humans
Immune Tolerance
Immunity, Innate
Male
Middle Aged
Polymorphism, Genetic
Receptors, CCR5
Sex Factors
T-Lymphocytes
Viral Load
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/172461
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