RESUMEN
The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.
Asunto(s)
Transmisión de Enfermedad Infecciosa , Evolución Molecular , Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/genética , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Vacunas contra el SIDA/inmunología , Secuencia de Bases , Variación Genética , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/inmunología , VIH-1/aislamiento & purificación , VIH-1/fisiología , Humanos , Modelos Biológicos , Datos de Secuencia Molecular , Mutación , Filogenia , ARN Viral/sangre , ARN Viral/genética , Receptores CCR5/metabolismo , Análisis de Secuencia de ARN , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunologíaRESUMEN
The purpose of the present investigation was to examine the effects of 30 days of treatment with a topical cream consisting of cetylated fatty acids on static postural stability and plantar pressures in patients with osteoarthritis (OA) of one or both knees. Forty patients diagnosed with knee OA were randomly assigned to 1 of 2 topical treatment groups: (a) cetylated fatty acid (CFA; N = 20; age = 62.7 +/- 11.7 years); or (b) placebo (P; N = 20; age = 64.6 +/- 10.5 years). Patients were tested on 2 occasions: (a) baseline (T1), and (b) following a 30-day treatment period consisting of cream application twice per day (T2). Assessments included 20- and 40-second quiet standing protocols on a force plate to measure center of pressure (COP) total excursion length, COP velocity, and rearfoot and forefoot plantar pressure distribution. In the CFA group, a significant reduction in the COP excursion length and velocity were observed at T2, whereas no significant differences were observed in the P group. No significant differences in mean forefoot, rearfoot, or rearfoot-to-forefoot plantar pressure ratios were observed in either group at T2. However, in a subgroup of participants designated to be right- or left-side dominant, improvements in the right-to-left forefoot plantar pressure ratios were observed in both groups. These data indicate that 30 days of treatment with a topical cream consisting of cetylated fatty acids improves static postural stability in patients with knee OA presumably due to pain relief during quiet standing. Such over-the-counter treatment may help improve the exercise trainability of people with OA.