RESUMEN
The reservoir of human immunodeficiency virus (HIV) in semen is unknown. Several lines of evidence suggest that semen HIV may not arise from the same reservoir of infection as peripheral blood. If true, the viral burden in the two compartments could be qualitatively and quantitatively different, a scenario of potentially profound significance for the design of effective strategies of treatment, disease monitoring, and infection containment. We report here that the ratio of infected to uninfected leukocytes in ejaculated semen specimens is highly discordant with paired blood samples, demonstrating that they derive from distinct populations of infected cells. In addition, infectious HIV was isolated from semen cells, but not from blood cells, of an individual on triple antiretroviral therapy; the absence of major resistance-conferring mutations in the semen virus indicates that it was replicating in isolation from the antiviral agents. The compartmentalization of blood and semen infection was further supported by genetic analysis of several infectious HIV clones isolated from semen cells and peripheral blood cells of another donor not on antiretroviral therapy. Protease gene sequence analyses revealed significant divergence of the two viral populations. These findings confirm the distinct compartmentalization of HIV in the semen of this study cohort, and support the concept that semen HIV arises from an isolated reservoir of infection that may function independently in the pathobiology of HIV disease.
Asunto(s)
Infecciones por VIH/virología , VIH/genética , Leucocitos/virología , Semen/virología , Secuencia de Aminoácidos , Estudios de Cohortes , Reservorios de Enfermedades , Variación Genética/genética , VIH/aislamiento & purificación , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Proteasa del VIH/genética , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Recuento de Leucocitos , Masculino , Datos de Secuencia Molecular , Filogenia , ARN Viral/análisis , ARN Viral/sangre , Semen/inmunologíaRESUMEN
Hormonal responses to oral paroxetine were examined in a group of healthy subjects. The calcium response to serotonin (5-hydroxytryptamine, 5HT), mediated by platelet 5HT2A, was also measured. Paroxetine elicited a cortisol response that was directly correlated with the magnitude of platelet calcium response. The cortisol response was also correlated with the trait of impulsivity. These results suggest that paroxetine may be a useful probe in studies of serotonergic systems.