A Genetic and Viral Load Analysis of the Simian Immunodeficiency Virus during the Acute Phase in Macaques Inoculated by the Vaginal Route

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Abstract
A comparative genetic analysis of SIV-infected female macaques during the first 120 days postinfection was undertaken. The same dose of a macaque-passaged SIVmac239(nef open) was administered to three macaques intravenously (IV) and to three macaques intravaginally (IVAG). Clinical outcomes observed ranged from rapid to nonprogression, while two of the IV-infected macaques developed an uncommon hindleg paresis. Analysis of viral load (bDNA assay) determined that both IV- and IVAG-infected macaques had comparable high viral loads at the observed viral peak of 14 days postinfection. A study of viral quasispecies diversity by the heteroduplex mobility assay indicated that (1) the IV-infected macaques had a highly heterogeneous quasispecies population similar to the infecting viral stock; and (2) in two of three IVAG-infected macaques multiple viral genotypes (minimum, three or four) were observed in blood and lymph tissues at early times postinfection, which indicated that limited numbers of viral variants crossed the vaginal mucosa and established infection. Therefore, the route of infection can clearly influence early viral selection and diversity. In addition, a third IVAG-infected macaque, which was a rapid progressor, did not seroconvert and progressed to AIDS in 120 days. This macaque exhibited a high viral load and heterogeneous quasispecies. These data demonstrate differences in the quasispecies complexity associated with route of infection and rate of disease progression.