TARGETING CELLULAR PROCESSES TO INHIBIT MONKEYPOX VIRUS INFECTION IN VIVO

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 2001年的恐怖主义事件使我们对我们目前的健康指导方针提出质疑，并重新评估重新开始大规模天花疫苗接种的利弊。 然而，用目前的牛痘（VV）疫苗制剂接种与显著的副作用相关，包括可导致永久性毁容或死亡的播散性VV感染。 最近一个描述与大规模疫苗接种相关的发病率和死亡率的模型表明，仅疫苗接种就可能导致190至285人死亡-即使在只有75%的人口接种疫苗和排除高度易感人群的情况下。 特别是在免疫功能低下的人，谁尚未被确定已感染了人类免疫缺陷病毒（艾滋病毒），预计将发生破坏性的影响。 因此，需要新的疫苗和治疗方法来对抗痘病毒作为生物恐怖剂的潜在用途，并保护个体免受与当前疫苗相关的潜在并发症。 不幸的是，针对天花的免疫保护机制或天花样疾病的发病机制尚未全部被确定，并且仅存在有限的药物靶点发现努力。 唯一能概括天花所有方面的动物模型是用猴痘病毒（MPV）感染非人灵长类动物（NHP），猴痘病毒是一种正痘病毒，在遗传上与天花相似，也感染人类并诱导与天花难以区分的疾病。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The terrorist events of 2001 have led us to question our current health guidelines and to re-evaluate the advantages and disadvantages of reinitiating wide-scale smallpox vaccination. However, vaccination with the current vaccinia (VV) vaccine preparation is associated with significant side effects, including disseminated VV infection that can lead to permanent disfiguration or mortality. A recent model describing the morbidity and mortality associated with mass vaccination suggests that 190 to 285 deaths will likely occur due to vaccination alone--even under conditions in which only 75% of the population is vaccinated and highly susceptible populates are excluded. Particularly devastating effects are expected to occur in immunocompromised individuals, who have yet been determined to have been infected with the human immunodeficiency virus (HIV). Thus, new vaccine and therapeutic approaches are needed to combat the potential use of poxviruses as bioterrorism agents, and to protect individuals from the potential complications associated with the current vaccine. Unfortunately, the mechanisms of immune protection against smallpox or the pathogenesis of smallpox-like diseases have not all been defined, and only limited drug target discovery efforts exist. The only animal model that recapitulates all aspects of smallpox is the infection of nonhuman primates (NHP) with monkeypox virus (MPV), an orthopox virus that is genetically similar to smallpox and also infects humans and induces disease that is indistinguishable from smallpox.