Human genes that limit AIDS

O’Brien, Stephen J.; Nelson, George W.

doi:10.1038/ng1369

Cited by 269 publications

(177 citation statements)

References 85 publications

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“…The identification of human genetic factors that determine the severity of HIV-1 infection has caused much excitement, and, to date. human genes have been shown to account for Ϸ10% of variability in disease progression rates (27). This leaves considerable scope for identifying other sources of variation, of which viral genetic factors have been underexplored.…”

Section: Discussionmentioning

confidence: 99%

Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesis

Fraser

Hollingsworth²,

Chapman³

et al. 2007

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

381

556

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The natural course of HIV-1 infection is characterized by a high degree of heterogeneity in viral load, not just within patients over time, but also between patients, especially during the asymptomatic stage of infection. Asymptomatic, or set-point, viral load has been shown to correlate with both decreased time to AIDS and increased infectiousness. The aim of this study is to characterize the epidemiological impact of heterogeneity in set-point viral load. By analyzing two cohorts of untreated patients, we quantify the relationships between both viral load and infectiousness and the duration of the asymptomatic infectious period. We find that, because both the duration of infection and infectiousness determine the opportunities for the virus to be transmitted, this suggests a trade-off between these contributions to the overall transmission potential. Some public health implications of variation in set-point viral load are discussed. We observe that set-point viral loads are clustered around those that maximize the transmission potential, and this leads us to hypothesize that HIV-1 could have evolved to optimize its transmissibility, a form of adaptation to the human host population. We discuss how this evolutionary hypothesis can be tested, review the evidence available to date, and highlight directions for future research.cohort studies ͉ life-history ͉ mathematical model ͉ trade-off ͉ virulence

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Section: Discussionmentioning

confidence: 99%

Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesis

Fraser

Hollingsworth²,

Chapman³

et al. 2007

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

381

556

View full text Add to dashboard Cite

show abstract

“…Allelic variants of the HLA molecule can bind and display various antigenic peptides with differing affinities, thereby influencing the efficiency of immune protection by both the specificity and affinity of peptide binding and recognition by T-cells [91]. Different HLA alleles specify cell-surface molecules with specific recognition sites for infectious agents, differential HIV)1 peptide motif recognition can influence both the time interval from infection to AIDS and the kinetics of HIV)1 adaptive escape from immune surveillance in an infected individual [92]. Other loci in the MHC can also play important roles in the HLA-TCR restriction system, influencing HLA assembly and antigen presentation, giving rise to individual variation in immune response.…”

Section: Europementioning

confidence: 99%

HLA and disease

Ghodke‐Puranik

Joshi

Chopra³

et al. 2005

Eur J Epidemiol

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Association of HLA and diseases is well known. Several population studies are available suggesting evidence of association of HLAs in more than 40 diseases. HLA found across various populations vary widely. Some of the reasons attributed for such variation are occurrence of social stratification based on geography, language and religion, consequences of founder effect, racial admixture or selection pressure due to environmental factors. Hence certain HLA alleles that are predominantly associated with disease susceptibility or resistance in one population may or may not show any association in other populations for the same disease. Despite of these limitations, HLA associations are widely studied across the populations worldwide and are found to be important in prediction of disease susceptibility, resistance and of evolutionary maintenance of genetic diversity. This review consolidates the HLA data on some prominent autoimmune and infectious diseases among various ethnic groups and attempts to pinpoint differences in Indian and other population.

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“…This variability is governed to a large extent by multiple host genetic factors including chemokine receptors, their ligands, MHC molecules, cytokines and their receptors [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%