Intra-host competition between nef-defective escape mutants and wild-type human immunodeficiency virus type 1.
Various forms of nef genes with deletions at conserved positions along the sequence have been reported to persist in human immunodeficiency virus type 1 infected patients. We investigate the forces maintaining such variants in the proviral population. The main selection pressures are preservation of function and host immune response. The crippled Nef protein might have fewer epitopes, and as such be less visible to the specific immune response, but it will lose some function. Does a trade-off between avoidance of the immune response and loss of function explain the dynamics of the crippled virus found in the patients? To answer this question, we formulated a deterministic model of the virus-host interactions. We found that when the crippled protein presents few epitopes and suffers little loss of function, the two viral types can coexist. Otherwise, the wild-type comes to prevail. The mutant form might initially dominate, but as the selective pressure by the CD84+ T cells decreases over the course of infection, the advantage for the crippled form of losing epitopes disappears. Hence, we go from a situation of coexistence of wild-type and mutant, to a situation of only full-length nef. The results are discussed in the context of the suggested use of live attenuated vaccines having deletions in nef.
Altes
H K
HK
Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, University of Oxford, UK. hester.korthalsaltes@ceid.ox.ac.uk
Jansen
V A
VA
D015754:Genes, nef; D014644:Genetic Variation; D015658:HIV Infections / Q000209:etiology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D009154:Mutation; D014613:Vaccines, Attenuated / Q000235:genetics; D014765:Viral Vaccines / Q000235:genetics
D014613:Vaccines, Attenuated; D014765:Viral Vaccines