Poxvirus interleukin-4 expression overcomes inherent resistance and vaccine-induced immunity: Pathogenesis, prophylaxis, and antiviral therapy

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• 作者：Nanhai Chen ; Clifford J. Bellone ; Jill Schriewer ; Gelita Owens ; Torgny Fredrickson ; Scott Parker ; R. Mark L. Buller
• 关键词：Immunosuppression ; Poxvirus ; Ectromelia virus ; Lethal infection ; IL-4
• 刊名：Virology
• 出版年：2011
• 出版时间：20 January 2011
• 年：2011
• 卷：409
• 期：2
• 页码：328-337
• 全文大小：892 K

文摘

In 2001, Jackson et al. reported that murine IL-4 expression by a recombinant ectromelia virus caused enhanced morbidity and lethality in resistant C57BL/6 mice as well as overcame protective immune memory responses. To achieve a more thorough understanding of this phenomenon and to assess a variety of countermeasures, we constructed a series of ECTV recombinants encoding murine IL-4 under the control of promoters of different strengths and temporal regulation. We showed that the ECTV-IL-4 recombinant expressing the highest level of IL-4 was uniformly lethal for C57BL/6 mice even when previously immunized. The lethality of the ECTV-IL-4 recombinants resulted from virus-expressed IL-4 signaling through the IL-4 receptor but was not due to IL-4 toxicity. A number of treatment approaches were evaluated against the most virulent IL-4 encoding virus. The most efficacious therapy was a combination of two antiviral drugs (CMX001^® and ST-246^®) that have different mechanisms of action.