RESUMO
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.
Assuntos
Soronegatividade para HIV , HIV-1 , Hemofilia A/epidemiologia , Adolescente , Adulto , Quimiocina CCL4 , Quimiocina CCL5/sangue , Criança , Estudos de Coortes , Contaminação de Medicamentos , Fator VIII/efeitos adversos , Fator VIII/isolamento & purificação , Fator VIII/uso terapêutico , Feminino , Predisposição Genética para Doença , Genótipo , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Soropositividade para HIV , Hemofilia A/genética , Hemofilia A/terapia , Temperatura Alta , Humanos , Imunidade Inata , Isoanticorpos/sangue , Ativação Linfocitária , Proteínas Inflamatórias de Macrófagos/sangue , Masculino , Polimorfismo Genético , Receptores CCR5/genética , RiscoAssuntos
Síndrome da Imunodeficiência Adquirida/etiologia , Modelos Animais de Doenças , Animais , Produtos do Gene nef/fisiologia , Produtos do Gene tat/fisiologia , Humanos , Macaca fascicularis , Macaca mulatta , Macaca nemestrina , Camundongos , Camundongos SCID , Camundongos Transgênicos , Papio , Coelhos , Síndrome de Imunodeficiência Adquirida dos Símios/etiologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana , Produtos do Gene tat do Vírus da Imunodeficiência HumanaRESUMO
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
