title: The coreceptor mutation CCR5Delta32 influences the dynamics of HIV epidemics and is selected for by HIV.
abstract: We explore the impact of a host genetic factor on heterosexual HIV epidemics by using a deterministic mathematical model. A protective allele unequally distributed across populations is exemplified in our models by the 32-bp deletion in the host-cell chemokine receptor CCR5, CCR5Delta32. Individuals homozygous for CCR5Delta32 are protected against HIV infection whereas those heterozygous for CCR5Delta32 have lower pre-AIDS viral loads and delayed progression to AIDS. CCR5Delta32 may limit HIV spread by decreasing the probability of both risk of infection and infectiousness. In this work, we characterize epidemic HIV within three dynamic subpopulations: CCR5/CCR5 (homozygous, wild type), CCR5/CCR5Delta32 (heterozygous), and CCR5Delta32/CCR5Delta32 (homozygous, mutant). Our results indicate that prevalence of HIV/AIDS is greater in populations lacking the CCR5Delta32 alleles (homozygous wild types only) as compared with populations that include people heterozygous or homozygous for CCR5Delta32. Also, we show that HIV can provide selective pressure for CCR5Delta32, increasing the frequency of this allele.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Sullivan
authors.forename: J
authors.initials: J
authors.lastname: Wigginton
authors.forename: D
authors.initials: D
authors.lastname: Kirschner
mesh_terms: D000483:Alleles; D004196:Disease Outbreaks; D005260:Female; D005787:Gene Frequency; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics* / Q000635:transmission; D020010:Heterosexuality; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008954:Models, Biological; D009154:Mutation; D019713:Receptors, CCR5 / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D019713:Receptors, CCR5