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灭活的口疮病毒在生殖器疱疹病毒感染的豚鼠模型中显示出具有疾病修饰的抗病毒活性。

Inactivated Orf-virus shows disease modifying antiviral activity in a guinea pig model of genital herpesvirus infection.

机构信息

Institute of Medical Immunology, Charité - Medical University Berlin, Germany.

Bayer AG, Leverkusen, Germany.

出版信息

J Microbiol Immunol Infect. 2018 Oct;51(5):587-592. doi: 10.1016/j.jmii.2017.03.002. Epub 2017 Jun 27.

DOI:10.1016/j.jmii.2017.03.002
PMID:28711432
Abstract

BACKGROUND

Inactivated Orf virus (iORFV) has been used as a preventative as well as a therapeutic immunomodulator in veterinary medicine in different species. iORFV elicits strong effects on cytokine secretion in mice and human immune cells leading to an auto-regulated loop of initial up-regulation of inflammatory and Th1-related cytokines followed by Th2-related cytokines that attenuate immunopathology. The therapeutic potential of iORFV has been recognized in several models for difficult-to-treat disease areas such as chronic viral diseases, liver fibrosis or various forms of cancer.

METHODS

Guinea pigs were infected with Human Herpesvirus (HSV)-2 strain MS and treated with iORFV, Acyclovir (ACV) or placebo, respectively. Clinical score of herpes lesions and viral shedding was assessed over a period of 40 days. In addition, viral DNA in dorsal root ganglia was quantified at the end of the study.

RESULTS

Disease symptoms were minimal or absent in iORFV-treated guinea pigs but tended to be severe in animals treated with either ACV or placebo. The cumulated disease score was significantly reduced in iORFV-treated but not in ACV- or placebo-treated guinea pigs. In addition, treatment with iORFV, but not ACV or placebo, led to significant reduction of viral DNA load in dorsal root ganglia.

CONCLUSION

iORFV effectively suppressed recurrences in guinea pigs experimentally infected with HSV. iORFV did not only reduce recurrent disease episodes but was, compared with ACV, more effective in reducing latency as measured by viral DNA detected in dorsal root ganglia of infected animals.

摘要

背景

已在兽医领域的不同物种中,将灭活的口疮病毒(iORFV)用作预防性和治疗性免疫调节剂。iORFV 可引起小鼠和人免疫细胞中的细胞因子分泌产生强烈影响,导致初始炎症和 Th1 相关细胞因子上调的自动调节环,随后是减轻免疫病理的 Th2 相关细胞因子。在几种难以治疗的疾病模型中,例如慢性病毒疾病、肝纤维化或各种形式的癌症中,已经认识到 iORFV 的治疗潜力。

方法

豚鼠感染人类单纯疱疹病毒(HSV)-2 株 MS 并分别用 iORFV、阿昔洛韦(ACV)或安慰剂治疗。在 40 天的时间内评估疱疹病变和病毒脱落的临床评分。此外,在研究结束时定量测定背根神经节中的病毒 DNA。

结果

iORFV 治疗的豚鼠疾病症状轻微或不存在,但用 ACV 或安慰剂治疗的动物的疾病症状往往严重。iORFV 治疗的豚鼠累积疾病评分显著降低,但 ACV 或安慰剂治疗的豚鼠则没有。此外,iORFV 治疗而非 ACV 或安慰剂治疗可导致背根神经节中的病毒 DNA 载量显著降低。

结论

iORFV 可有效抑制 HSV 感染的豚鼠复发。iORFV 不仅减少了复发性疾病发作,而且与 ACV 相比,在减少潜伏感染动物背根神经节中检测到的病毒 DNA 方面更有效。

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