RESUMO
BACKGROUND: The sooty mangabey is a vulnerable West African species that naturally harbors simian immunodeficiency virus (SIV) without pathological symptoms. We present normative hematology and serum chemistry values for this species. METHODS: Hematology analytes from 136 females and 96 males and serum chemistry analytes from 57 females and 26 males were studied. RESULTS: Values of several analytes fell outside published reference ranges in the rhesus monkey, a laboratory standard for Old World primates. Erythrocyte-related parameters were higher in mangabeys than in rhesus monkeys, while platelet counts were lower. Mangabeys also had higher gamma-glutamyltransferase levels and lower urea nitrogen levels. Males had higher erythrocyte-associated values than females. Albumin, globulin, albumin/globulin ratio, calcium, and creatinine changed with age in patterns similar to those reported for the rhesus monkey. CONCLUSIONS: The unique blood profile of the mangabey should be taken into account in clinical and experimental studies of this species.
Assuntos
Cercocebus atys/sangue , Macaca mulatta/sangue , Animais , Análise Química do Sangue , Feminino , Testes Hematológicos , Masculino , Valores de Referência , Fatores SexuaisRESUMO
A key feature differentiating nonpathogenic SIV infection of sooty mangabeys (SMs) from pathogenic HIV/SIV infections is the rapid resolution of type I IFN (IFN-I) responses and IFN-stimulated gene expression during the acute-to-chronic phase transition and the establishment of an immune quiescent state that persists throughout the chronic infection. We hypothesized that low levels of IFN-I signaling may help to prevent chronic immune activation and disease progression in SIV-infected SMs. To assess the effects of IFN-I signaling in this setting, in the present study, we administered recombinant rhesus macaque IFNα2-IgFc (rmIFNα2) to 8 naturally SIV-infected SMs weekly for 16 weeks. Gene-expression profiling revealed a strong up-regulation of IFN-stimulated genes in the blood of treated animals, confirming the reagent's bioactivity. Interestingly, we observed an approximately 1-log decrease in viral load that persisted through day 35 of treatment. Flow cytometric analysis of lymphocytes in the blood, lymph nodes, and rectal biopsies did not reveal a significant decline of CD4(+) T cells, a robust increase in lymphocyte activation, or change in the level of SIV-specific CD8(+) T cells. The results of the present study indicate that administration of type I IFNs in SIV-infected SMs induces a significant anti-viral effect that is not associated with a detectable increase in chronic immune activation.
Assuntos
Cercocebus atys/virologia , Interferon Tipo I/agonistas , Ativação Linfocitária/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Replicação Viral/efeitos dos fármacos , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células/efeitos dos fármacos , Cercocebus atys/sangue , Cercocebus atys/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interferon Tipo I/administração & dosagem , Interferon Tipo I/farmacologia , Depleção Linfocítica , Macaca mulatta/imunologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Especificidade da Espécie , Carga Viral/efeitos dos fármacos , Viremia/sangue , Viremia/imunologia , Viremia/virologiaRESUMO
Naturally SIV-infected sooty mangabeys (SMs) remain asymptomatic despite high virus replication. Elucidating the mechanisms underlying AIDS resistance of SIV-infected SMs may provide crucial information to better understand AIDS pathogenesis. In this study, we assessed the determinants of set-point viremia in naturally SIV-infected SMs, i.e., immune control of SIV replication versus target cell limitation. We depleted CD4+ T cells in 6 naturally SIV-infected SMs by treating with humanized anti-CD4 mAb (Cdr-OKT4A-huIgG1). CD4+ T cells were depleted almost completely in blood and BM and at variable levels in mucosal tissues and LNs. No marked depletion of CD14+ monocytes was observed. Importantly, CD4+ T cell depletion was associated with a rapid, significant decline in viral load, which returned to baseline level at day 30-45, coincident with an increased fraction of proliferating and activated CD4+ T cells. Throughout the study, virus replication correlated with the level of proliferating CD4+ T cells. CD4+ T cell depletion did not induce any changes in the fraction of Tregs or the level of SIV-specific CD8+ T cells. Our results suggest that the availability of activated CD4+ T cells, rather than immune control of SIV replication, is the main determinant of set-point viral load during natural SIV infection of SMs.