EFFICACY OF S26308 AGAINST GUINEA-PIG CYTOMEGALO-VIRUS INFECTION
EFFICACY OF S26308 AGAINST GUINEA-PIG CYTOMEGALO-VIRUS INFECTION
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DOI：
10.1128/aac.32.5.678
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发表时间：
1988-05-01
影响因子：
4.9
通讯作者：
HSIUNG, GD
中科院分区：
文献类型：
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作者：
CHEN, M;GRIFFITH, BP;HSIUNG, GD
预防性使用抗巨细胞病毒（CMV）的抗病毒剂特别适用于免疫功能低下的宿主，因为CMV引起的发病率和死亡率最常发生在免疫抑制后。我们已经评估了新的Riker化合物S26308在豚鼠中对CMV的治疗和预防性抗病毒活性。在体外豚鼠胚胎细胞中以及在免疫活性豚鼠和免疫受损豚鼠中评估了化合物的疗效。 豚鼠CMV空斑形成仅在病毒感染前用S26308处理的细胞中减少。即使在病毒吸收后除去化合物，抗病毒活性仍然存在，这既不是由于病毒破坏也不是由于细胞生长抑制。与假处理动物相比，在病毒接种前24小时开始S26308治疗的豚鼠中病毒血症的频率降低。病毒血症频率的降低并不能阻止病毒扩散到靶组织，但确实降低了免疫功能低下豚鼠中CMV诱导疾病的严重程度。在S26308处理的细胞的上清液中检测到低水平的干扰素，并且在给予S26308的豚鼠的血清中检测到干扰素。这些结果表明，S26308在体内和体外均能诱导干扰素，降低CMV感染性。这种抗病毒活性，虽然温和，伴随着有益的影响CMV诱导的发病率和死亡率。预防性使用S26308与其他治疗药物的组合可能是一个有用的策略，对CMV感染。
Prophylactic use of antiviral agents against cytomegalovirus (CMV) is particularly indicated for the immunocompromised host because morbidity and mortality due to CMV occur most frequently following immunosuppression. We have evaluated the new Riker compound S26308 for its therapeutic and prophylactic antiviral activity against CMV in guinea pigs. The efficacy of the compound was assessed in vitro in guinea pig embryo cells and in vivo in both immunocompetent and immunocompromised guinea pigs. Guinea pig CMV plaque formation was reduced only in cells treated with S26308 prior to virus infection. The antiviral activity remained even when the compound was removed after virus absorption and was due to neither virus destruction nor inhibition of cell growth. The frequency of viremia was reduced in guinea pigs for which S26308 therapy was initiated 24 h prior to virus inoculation compared with sham-treated animals. This reduction in the frequency of viremia did not prevent virus spread to target tissues but did result in a reduction of the severity of CMV-induced disease in immunocompromised guinea pigs. Low levels of interferon were detected in supernatants of S26308-treated cells, and interferon was detected in the serum of guinea pigs given S26308. These results indicate that S26308 can induce interferon and reduce CMV infectivity in vivo and in vitro when used prophylactically. This antiviral activity, although modest, was accompanied by beneficial effects on CMV-induced morbidity and mortality. Prophylactic use of S26308 in combination with other therapeutic agents may be a useful strategy against CMV infections.