Envelope diversity, coreceptor usage and syncytium-inducing phenotype of HIV-1 variants in saliva and blood during primary infection

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Abstract
To determine whether oral fluids can serve as a model for studying HIV-1 shedding, we compared the genetic diversity, coreceptor use, and syncytium-inducing (SI) phenotype of viral variants in saliva and blood during primary HIV-1 infection. Observational cross-sectional cohort study. Blood plasma and saliva were sampled from 17 men early in primary HIV-1 infection. Viral diversity, predicted X4/R5 genotype and SI phenotype in samples were determined by heteroduplex tracking assays (HTAs) targeting the V1/V2 and V3 gp120 regions, sequence analyses and MT-2 cell assay. Identical or very similar HTA banding and deduced amino acid sequence patterns in the V1/V2 and V3-encoding regions were observed between paired fluids of each subject. As assessed by V1/V2 HTA, 10 subjects had a single major viral variant and seven subjects exhibited multiple yet highly related variants. Two subjects had V1/V2 variants in blood that were identical to saliva but present in different relative abundances. A sexual transmission pair exhibited genetically dissimilar variants, suggesting transmission of a minor variant or rapid evolution during initial viremia. All subjects harbored R5 non-SI variants. Relatively homogenous viral populations detected in plasma and saliva prior to seroconversion suggests that HIV-1 is disseminated to oral fluids early in infection and reflects the quasispecies in blood. These findings suggest that the oral cavity may serve as an easily accessible surrogate model for studying the dynamics of HIV-1 shedding at mucosal sites.