The coreceptor mutation CCR5Δ32 influences the dynamics of HIV epidemics and is selected for by HIV

Sullivan, Amy D.; Wigginton, Janis E.; Kirschner, Denise E.

doi:10.1073/pnas.181325198

Cited by 41 publications

(31 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STD models based on frequency-dependent transmission-the classical analytic formulation-are published often and prominently, typically nested in models addressing larger topics such as drug resistance or competition between strains (e.g. Thrall & Antonovics 1997;Blower et al 1998Blower et al , 2000Bowden & Garnett 2000;Sullivan et al 2001;Boots & Knell 2002). In their review of STD modelling, Anderson & Garnett (2000) point out that simpler models are complementary to complex simulations and help to extract general principles and reach robust conclusions, which aid in policy development (though see Garnett et al (1999) for a discussion of potential shortcomings).…”

Section: Introductionmentioning

confidence: 99%

Frequency–dependent incidence in models of sexually transmitted diseases: portrayal of pair–based transmission and effects of illness on contact behaviour

Lloyd‐Smith

Getz

Westerhoff³

2004

Proc. R. Soc. Lond. B

View full text Add to dashboard Cite

We explore the transmission process for sexually transmitted diseases (STDs). We derive the classical frequency-dependent incidence mechanistically from a pair-formation model, using an approximation that applies to populations with rapid pairing dynamics (such as core groups or non-pair-bonding animals). This mechanistic derivation provides a framework to assess how accurately frequency-dependent incidence portrays the pair-based transmission known to underlie STD dynamics. This accuracy depends strongly on the disease being studied: frequency-dependent formulations are more suitable for chronic less-transmissible infections than for transient highly transmissible infections. Our results thus support earlier proposals to divide STDs into these two functional classes, and we suggest guidelines to help assess under what conditions each class can be appropriately modelled using frequency-dependent incidence. We then extend the derivation to include situations where infected individuals exhibit altered pairing behaviour. For four cases of increasing behavioural complexity, analytic expressions are presented for the generalized frequency-dependent incidence rate, basic reproductive number (R 0 ) and steady-state prevalence (i ϱ ) of an epidemic. The expression for R 0 is identical for all cases, giving refined insights into determinants of invasibility of STDs. Potentially significant effects of infection-induced changes in contact behaviour are illustrated by simulating epidemics of bacterial and viral STDs. We discuss the application of our results to STDs (in humans and animals) and other infectious diseases.

show abstract

Section: Introductionmentioning

confidence: 99%

Frequency–dependent incidence in models of sexually transmitted diseases: portrayal of pair–based transmission and effects of illness on contact behaviour

Lloyd‐Smith

Getz

Westerhoff³

2004

Proc. R. Soc. Lond. B

View full text Add to dashboard Cite

show abstract

“…Despite intense research, only a relatively small number of regions and genes have been directly implicated as targets of selection in the human genome (Kitano and Saitou 1999;Rana et al 1999;Huttley et al 2000;Hollox et al 2001;Hull et al 2001;Hurst and Pal 2001;Koda et al 2001;Sullivan et al 2001;Tishkoff et al 2001;Baum et al 2002;Fullerton et al 2002;Gilad et al 2002;Hamblin et al 2002). A more comprehensive and genomic understanding of how and where natural selection has shaped patterns of genetic variation may provide important insights into the mechanisms of evolutionary change (Otto 2000), guide selection of loci for inclusion in population genetic studies (Vitalis et al 2001), facilitate the annotation of functionally significant genomic regions (Nielsen 2001), and help elucidate genotype-phenotype correlations in complex diseases (Przeworski et al 2000;Nielsen 2001).…”

mentioning

confidence: 99%

Interrogating a High-Density SNP Map for Signatures of Natural Selection

Akey¹,

Zhang²,

Zhang³

et al. 2002

Genome Res.

857

838

View full text Add to dashboard Cite

Identifying genomic regions that have been targets of natural selection remains one of the most important and challenging areas of research in genetics. To this end, we report an analysis of 26,530 single nucleotide polymorphisms (SNPs) with allele frequencies that were determined in three populations. Specifically, we calculated a measure of genetic differentiation, FST, for each locus and examined its distribution at the level of the genome, the chromosome, and individual genes. Through a variety of analyses, we have found statistically significant evidence supporting the hypothesis that selection has influenced extant patterns of human genetic variation. Importantly, by contrasting the FST of individual SNPs to the empirical genome-wide distribution of FST, our results are not confounded by tenuous assumptions of population demographic history. Furthermore, we have identified 174 candidate genes with distribution of genetic variation that indicates that they have been targets of selection. Our work provides a first generation natural selection map of the human genome and provides compelling evidence that selection has shaped extant patterns of human genomic variation

show abstract

“…Depletion (or neutralization) of the cytokine IL-17 was shown to be a necessary factor in development of acquired immunity to Streptococcus pneumoniae (Lu et al, 2008). Humans with the mutation CCR5D32 are missing the chemokine receptor CCR5 and are protected from HIV-1 infection (Sullivan et al, 2001). As a final example, patients with latent TB who are treated with anti-tumour necrosis factor (TNF) drugs for their rheumatoid arthritis suffer reactive TB, suggesting that TNF plays a major role in containing infection (Wallis et al, 2004).…”

Section: Example 4: Modelling Approaches To Complement Genetic Deletimentioning

confidence: 99%

Mathematical and computational approaches can complement experimental studies of host-pathogen interactions

Kirschner

Linderman

2008

Cellular Microbiology

View full text Add to dashboard Cite

SummaryIn addition to traditional and novel experimental approaches to study host-pathogen interactions, mathematical and computer modelling have recently been applied to address open questions in this area. These modelling tools not only offer an additional avenue for exploring disease dynamics at multiple biological scales, but also complement and extend knowledge gained via experimental tools. In this review, we outline four examples where modelling has complemented current experimental techniques in a way that can or has already pushed our knowledge of host-pathogen dynamics forward. Two of the modelling approaches presented go hand in hand with articles in this issue exploring fluorescence resonance energy transfer and two-photon intravital microscopy. Two others explore virtual or 'in silico' deletion and depletion as well as a new method to understand and guide studies in genetic epidemiology. In each of these examples, the complementary nature of modelling and experiment is discussed. We further note that multi-scale modelling may allow us to integrate information across length (molecular, cellular, tissue, organism, population) and time (e.g. seconds to lifetimes). In sum, when combined, these compatible approaches offer new opportunities for understanding host-pathogen interactions.

show abstract

The coreceptor mutation CCR5Δ32 influences the dynamics of HIV epidemics and is selected for by HIV

Cited by 41 publications

References 63 publications

Frequency–dependent incidence in models of sexually transmitted diseases: portrayal of pair–based transmission and effects of illness on contact behaviour

Frequency–dependent incidence in models of sexually transmitted diseases: portrayal of pair–based transmission and effects of illness on contact behaviour

Interrogating a High-Density SNP Map for Signatures of Natural Selection

Mathematical and computational approaches can complement experimental studies of host-pathogen interactions

Contact Info

Product

Resources

About