Heller M, Vasconcelos D, Cummins J, Oglesbee M
Department of Veterinary Biosciences, The Ohio State University, Columbus 43210, USA.
Antiviral Res. 1998 Jun;38(3):195-207. doi: 10.1016/s0166-3542(98)00017-5.
Cellular levels of heat shock proteins (HSPs) are elevated in response to physiologic states accompanying acute virus infection (e.g. fever). The objective of the present work was to define the antiviral effect of purified human lymphoblastoid IFN in the presence of HSP over-expression. For this purpose, canine distemper virus (CDV) was used since the response of CDV transcription and persistent infection phenotype to elevated HSP is characterized. First, the effect of elevated HSP on CDV lytic infection phenotype in Vero and CV1 cells was defined, and results extended to the closely related measles virus (MV). Cells expressing elevated levels of the major inducible 70-kDa HSP (hsp72) supported the emergence of large plaque variants of both CDV and MV from small plaque purified inocula. IFN treatment concurrent with infection caused a dosage-dependent reduction in the expression of large plaque variants without affecting hsp72 levels or total plaque number. In contrast to the stress response-induced large plaque variant, small plaques were resistant to the antiviral effects of IFN. These data demonstrate the ability of IFN to selectively abrogate the pro-viral effects of HSP over-expression, inhibiting the formation of a plaque phenotype that is correlated to enhanced virulence in animal models of morbillivirus encephalitis.
热休克蛋白（HSPs）的细胞水平会因急性病毒感染（如发烧）伴随的生理状态而升高。本研究的目的是确定在HSP过表达情况下纯化的人淋巴母细胞干扰素的抗病毒作用。为此，使用犬瘟热病毒（CDV），因为其对CDV转录和持续感染表型对HSP升高的反应已有特征描述。首先，确定了HSP升高对Vero和CV1细胞中CDV裂解感染表型的影响，并将结果扩展至密切相关的麻疹病毒（MV）。表达高水平主要诱导型70 kDa HSP（hsp72）的细胞支持从纯化的小斑块接种物中出现CDV和MV的大斑块变体。感染时同时进行干扰素处理导致大斑块变体的表达呈剂量依赖性降低，而不影响hsp72水平或总斑块数。与应激反应诱导产生的大斑块变体相反，小斑块对干扰素的抗病毒作用具有抗性。这些数据证明了干扰素能够选择性消除HSP过表达的促病毒作用，抑制与麻疹病毒脑炎动物模型中增强毒力相关的斑块表型的形成。
