RESUMEN
Mechanisms that protect most high-risk HIV-1 seronegative (HRSN) persons are not well understood. Among hemophiliacs from the Multicenter Hemophilia Cohort Study who remained HIV-1 seronegative despite a high (94%) risk for acquisition of HIV-1 infection, only 7/43 were homozygous for the protective CCR5 Delta32 polymorphism. Among the remainder, neither CCR5 density nor beta-chemokine production, nor in vitro susceptibility to infection with the HIV-1 isolate JR-FL could distinguish HRSN hemophiliacs from healthy controls. When compared to lymphocytes of healthy controls not at risk for HIV-1 infection, diminished spontaneous lymphocyte proliferation was seen in lymphocytes of HRSN hemophiliacs as well as in lymphocytes of hemophiliacs not at risk for HIV-1 infection. Surprisingly sera/plasmas obtained from high-risk HIV-1 seropositve hemophiliacs prior to seroconversion more often contained alloreactive antibodies than date-matched sera/plasmas obtained from HRSN hemophiliacs. Thus alloreactivity may predispose to acquisition of HIV-1 infection after parenteral exposure.
Asunto(s)
Seronegatividad para VIH , VIH-1 , Hemofilia A/epidemiología , Adolescente , Adulto , Quimiocina CCL4 , Quimiocina CCL5/sangre , Niño , Estudios de Cohortes , Contaminación de Medicamentos , Factor VIII/efectos adversos , Factor VIII/aislamiento & purificación , Factor VIII/uso terapéutico , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Seropositividad para VIH , Hemofilia A/genética , Hemofilia A/terapia , Calor , Humanos , Inmunidad Innata , Isoanticuerpos/sangre , Activación de Linfocitos , Proteínas Inflamatorias de Macrófagos/sangre , Masculino , Polimorfismo Genético , Receptores CCR5/genética , RiesgoAsunto(s)
Síndrome de Inmunodeficiencia Adquirida/etiología , Modelos Animales de Enfermedad , Animales , Productos del Gen nef/fisiología , Productos del Gen tat/fisiología , Humanos , Macaca fascicularis , Macaca mulatta , Macaca nemestrina , Ratones , Ratones SCID , Ratones Transgénicos , Papio , Conejos , Síndrome de Inmunodeficiencia Adquirida del Simio/etiología , Productos del Gen nef del Virus de la Inmunodeficiencia Humana , Productos del Gen tat del Virus de la Inmunodeficiencia HumanaRESUMEN
AIDS viruses require an intact functional nef gene in order to induce disease. The nonpathogenic molecular cloned virus SIVmac239nef-deletion encodes a truncated nef gene. This attenuated reading frame is expressed both in vitro and in a virus-infected animal in vivo. Encoding the first 58 amino acids of Nef, the reading frame retained its ability to down-modulate CD4 from the surface of T cells. CD4-down-modulated stable cell lines expressing full-length and truncated nef genes were significantly less infected by SIV. SIVmac239nef-open and SIVmacnef-deletion encoding a truncated nef clearly differed in replication kinetics in H9 cells and H9-derived cell lines. SIVmac239nef-deletion replication was delayed in H9. Copyright 1996 S. Karger AG, Basel