RESUMEN
HIV is difficult to eradicate due to the persistence of a long-lived reservoir of latently infected cells. Previous studies have shown that natural killer cells are important to inhibiting HIV infection, but it is unclear whether the administration of natural killer cells can reduce rebound viremia when anti-retroviral therapy is discontinued. Here we show the administration of allogeneic human peripheral blood natural killer cells delays viral rebound following interruption of anti-retroviral therapy in humanized mice infected with HIV-1. Utilizing genetically barcoded virus technology, we show these natural killer cells efficiently reduced viral clones rebounding from latency. Moreover, a kick and kill strategy comprised of the protein kinase C modulator and latency reversing agent SUW133 and allogeneic human peripheral blood natural killer cells during anti-retroviral therapy eliminated the viral reservoir in a subset of mice. Therefore, combinations utilizing latency reversal agents with targeted cellular killing agents may be an effective approach to eradicating the viral reservoir.
Asunto(s)
Fármacos Anti-VIH/farmacología , Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/terapia , VIH-1/efectos de los fármacos , Células Asesinas Naturales/inmunología , Inhibidores de Proteínas Quinasas/farmacología , Viremia/terapia , Animales , Médula Ósea/efectos de los fármacos , Médula Ósea/inmunología , Médula Ósea/virología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/virología , Técnicas de Cocultivo , Femenino , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/genética , VIH-1/inmunología , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Células Asesinas Naturales/trasplante , Masculino , Ratones , Ratones Transgénicos , Proteína Quinasa C/genética , Proteína Quinasa C/inmunología , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/virología , Carga Viral/efectos de los fármacos , Viremia/genética , Viremia/inmunología , Viremia/virología , Latencia del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
Patients with Type 2 diabetes are increasingly turning to the Web for information about diabetes and self-management. These sites, however, fail to address the cultural and linguistic needs of the growing community of Latinos with diabetes. The Juntos Controlamos la Diabetes Web site was designed as a low-cost patient education tool to be used by patients, caregivers, and healthcare providers to provide ongoing information about diabetes self-management tailored to the needs of the regional Latino community.