Farias Kleber Juvenal Silva, Machado Paula Renata Lima, Muniz José Augusto Pereira Carneiro, Imbeloni Aline Amaral, da Fonseca Benedito Antônio Lopes
1 Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo , São Paulo, Brazil .
Viral Immunol. 2015 Apr;28(3):161-9. doi: 10.1089/vim.2014.0090. Epub 2015 Feb 9.
Dengue virus (DENV) of the Flaviviridae family is a single positive-stranded RNA virus that is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. The objective of this study was to investigate the use of chloroquine (CLQ) as an antiviral drug against dengue virus in monkeys. To analyze the action of the drug in vivo, nonhuman primates groups (Aotus azarai infulatus) were inoculated with a subcutaneous injection of a virulent strain of DENV-2, treated and untreated CLQ. Blood hematological, viremia, and serum biochemical values were obtained from 16 DENV-2-inoculated, treated and untreated; four received only CLQ and one mock-infected Aotus monkeys. Monkey serum samples (day 0-10 post-inoculation) were assayed by reverse transcription polymerase chain reaction and Cytometric Bead Array for determination of viremia and inflammatory cytokines, respectively. Additionally, body temperature and activity levels were determined. In the present work, CLQ was effective on replication of DENV-2 in Aotus monkeys; a time viremia reduction was observed compared with the controls. The concentration of tumor necrosis factor alpha and interferon gamma in the serum of the animals had a statistically significant reduction in the groups treated with CLQ after infection compared with the controls. A significant decrease in systemic levels of the liver enzyme aspartate aminotransferase (AST) was also observed in the animals treated with CLQ after infection compared with the controls. These results suggest that CLQ interferes in DENV-2 replication in Aotus monkeys.
黄病毒科的登革病毒(DENV)是一种单正链RNA病毒,通过埃及伊蚊和白纹伊蚊传播。本研究的目的是调查氯喹(CLQ)作为抗登革病毒的抗病毒药物在猴子体内的应用。为了分析该药物在体内的作用,将非人类灵长类动物组(阿扎拉吼猴指名亚种)皮下注射强毒株DENV-2,分为接受和未接受CLQ治疗两组。从16只接种DENV-2、接受和未接受治疗的猴子;4只仅接受CLQ治疗的猴子以及1只假感染的阿扎拉吼猴获取血液血液学、病毒血症和血清生化值。分别通过逆转录聚合酶链反应和细胞计数微球阵列检测猴子血清样本(接种后0至10天),以测定病毒血症和炎性细胞因子。此外,还测定了体温和活动水平。在本研究中,CLQ对阿扎拉吼猴体内DENV-2的复制有效;与对照组相比,观察到病毒血症出现时间缩短。与对照组相比,感染后接受CLQ治疗的动物血清中肿瘤坏死因子α和干扰素γ的浓度有统计学意义的降低。与对照组相比,感染后接受CLQ治疗的动物血清中天冬氨酸转氨酶(AST)的全身水平也显著降低。这些结果表明,CLQ干扰了阿扎拉吼猴体内DENV-2的复制。