The impact of host genetic variation on infection with HIV-1

McLaren, Paul J.; Carrington, Mary

doi:10.1038/ni.3147

Cited by 129 publications

(117 citation statements)

References 74 publications

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“…Thus, HLA class I alleles that have an impact on outcome of HCV infection may also be involved in outcome of HBV infection. This is in line with the observation that HLA-B * 27 and B * 57 are not only linked to HCV clearance, but also the elite control and long-term non-progression in HIV infection [79] . To date, only few HBV-specific CD8+ T-cell epitopes have been described that are not restricted by HLA-A * 02 ( table 2 ).…”

Section: Impact Of Hla Class I Alleles On Disease Outcome and Virus-ssupporting

confidence: 74%

CD8+ T-Cell Responses in Hepatitis B and C: The (HLA-) A, B, and C of Hepatitis B and C

Nitschke

Luxenburger

Kiraithe

et al. 2016

Dig Dis

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Approximately 500 million people are chronically infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV) worldwide and are thus at high risk of progressive liver disease, leading to liver fibrosis, cirrhosis and ultimately hepatocellular cancer. Virus-specific CD8+ T-cells play a major role in viral clearance in >90% of adult patients who clear HBV and in approximately 30% of patients who clear HCV in acute infection. However, several mechanisms contribute to the failure of the adaptive CD8+ T-cell response in those patients who progress to chronic infection. These include viral mutations leading to escape from the CD8+ T-cell response as well as exhaustion and dysfunction of virus-specific CD8+ T-cells. Antiviral efficacy of the virus-specific CD8+ T-cell response also strongly depends on its restriction by specific human leukocyte antigens (HLA) class I alleles. Our review will summarize the role of HLA-A, B and C-restricted CD8+ T-cells in HBV and HCV infection. Due to the current lack of a comprehensive database of HBV- and HCV-specific CD8+ T-cell epitopes, we also provide a summary of the repertoire of currently well-described HBV- and HCV-specific CD8+ T-cell epitopes. A better understanding of the factors that contribute to the success or failure of virus-specific CD8+ T-cells may help to develop new therapeutic options for HBV eradication in patients with chronic HBV infection (therapeutic vaccination and/or immunomodulation) as well as a prophylactic vaccine against HCV infection.

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Section: Impact Of Hla Class I Alleles On Disease Outcome and Virus-ssupporting

confidence: 74%

CD8+ T-Cell Responses in Hepatitis B and C: The (HLA-) A, B, and C of Hepatitis B and C

Nitschke

Luxenburger

Kiraithe

et al. 2016

Dig Dis

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“…Several of them were reported in a previous HIV G2G analysis, which was performed in a very homogeneous human population and only corrected for population stratification on the viral side. Our G2G analysis of HIV did not identify new association, but confirmed the known HLA associations (Bartha et al, 2013; McLaren and Carrington, 2015). However, because of the extensive LD in the MHC region, determining a causal effect of the indexed SNPs will require elaborate population genetics, molecular genetics and functional assays.…”

Section: Discussionsupporting

confidence: 83%

“…Important inter-individual differences can be observed in human responses to infections, and in recent years researchers have started to explore the genetic underpinning of this phenotypic diversity (Prugnolle et al, 2005; Vannberg et al, 2011; Chapman and Hill, 2012; Rausell and Telenti, 2014; McLaren and Carrington, 2015). A better understanding of host-pathogen interactions at the genomic level could help explain pathogenesis, predict disease outcome or develop new therapeutics or vaccines.…”

Section: Introductionmentioning

confidence: 99%

Correcting for Population Stratification Reduces False Positive and False Negative Results in Joint Analyses of Host and Pathogen Genomes

et al. 2018

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Studies of host genetic determinants of pathogen sequence variations can identify sites of genomic conflicts, by highlighting variants that are implicated in immune response on the host side and adaptive escape on the pathogen side. However, systematic genetic differences in host and pathogen populations can lead to inflated type I (false positive) and type II (false negative) error rates in genome-wide association analyses. Here, we demonstrate through a simulation that correcting for both host and pathogen stratification reduces spurious signals and increases power to detect real associations in a variety of tested scenarios. We confirm the validity of the simulations by showing comparable results in an analysis of paired human and HIV genomes.

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“…The selection of these APOL1 resistance alleles by trypanosomiasis may account for the higher rate of kidney sclerosis in African homozygotes, an evolutionary pattern that is reminiscent of sickle-cell disease being favored by malaria (157,158). Finally, some polymorphisms have been shown to be associated with the rate of progression toward clinical disease in HIV-infected patients (159,160). Globally however, the purely polygenic theory, inspired by the "common disease, common variant" model created some confusion between the impact of infection on the human genome and the genetic determinism of infectious disease.…”

Section: Common Variants and Infectious Diseasesmentioning

confidence: 99%

Human genetic basis of interindividual variability in the course of infection

Casanova

2015

Proc. Natl. Acad. Sci. U.S.A.

161

111

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The key problem in human infectious diseases was posed at the turn of the 20th century: their pathogenesis. For almost any given virus, bacterium, fungus, or parasite, life-threatening clinical disease develops in only a small minority of infected individuals. Solving this infection enigma is important clinically, for diagnosis, prognosis, prevention, and treatment. Some microbes will inevitably remain refractory to, or escape vaccination, or chemotherapy, or both. The solution also is important biologically, because the emergence and evolution of eukaryotes alongside more rapidly evolving prokaryotes, archaea, and viruses posed immunological challenges of an ecological and evolutionary nature. We need to study these challenges in natural, as opposed to experimental, conditions, and also at the molecular and cellular levels. According to the human genetic theory of infectious diseases, inborn variants underlie life-threatening infectious diseases. Here I review the history of the field of human genetics of infectious diseases from the turn of the 19th century to the second half of the 20th century. This paper thus sets the scene, providing the background information required to understand and appreciate the more recently described monogenic forms of resistance or predisposition to specific infections discussed in a second paper in this issue.

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The impact of host genetic variation on infection with HIV-1

Cited by 129 publications

References 74 publications

CD8+ T-Cell Responses in Hepatitis B and C: The (HLA-) A, B, and C of Hepatitis B and C

CD8+ T-Cell Responses in Hepatitis B and C: The (HLA-) A, B, and C of Hepatitis B and C

Correcting for Population Stratification Reduces False Positive and False Negative Results in Joint Analyses of Host and Pathogen Genomes

Human genetic basis of interindividual variability in the course of infection

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