IMMUNE CONTROL OF EQUINE INFECTIOUS ANEMIA LENTIVIRUS

描述：主要研究者提议检验假设 保守的马传染性贫血病毒（EIAV）蛋白表位 通过CTLm从携带者马中鉴定的CTLm可用于诱导保护性 免疫系统的反应。 研究将集中在 可能为CD 8+的作用提供确凿证据的实验 EIAV控制中的CTL。 大多数免疫活性的马终止了最初的 病毒血症和病毒血症复发最终变得不明显 携带者的病毒水平非常低。 终止病毒血症需要 淋巴细胞反应;这些似乎与病毒更一致 而中和抗体则出现在 病毒血症已被终止。 为了提供数据 关于MHC I类限制性T淋巴细胞 CD 8 CTL和控制EIAV感染，主要研究者将 本研究的主要目的是：（1）鉴定EIAV保守抗原表位 由同种异体抗原ELA-A5限制性记忆CTL（CTLm）识别， 携带者马;（2）用逆转录病毒载体在马中诱导CTLm 表达保守的CTL表位;（3）确定是否共- 通过逆转录病毒载体表达马IL-12和CTL表位将 增加CTLm的频率;以及（4）确定是否 表达至少一个ELA-A5等位基因的免疫马受到保护 从或更有效地控制EIAV感染和疾病， 病毒挑战

DESCRIPTION: The principal investigator proposes to test the hypothesis that conserved equine infectious anemia virus (EIAV) protein epitopes identified by CTLm from carrier horses can be used to induce protective immune responses in naive horses. The research will focus on experiments that may provide conclusive evidence for the role of CD8+ CTL in EIAV control. Most immunocompetent horses terminate the initial viremia and recurrences of viremia to eventually become inapparent carriers with very low levels of virus. Termination of viremia requires lymphocyte responses; these appear to be more concordant with virus downregulation than do neutralizing antibodies, which appear after viremia has been terminated. With the intent of providing data concerning a cause/effect relationship between MHC class I-restricted CD8 CTL and control of EIAV infection, the principal investigator will address four specific aims: (1) To identify conserved EIAV epitopes recognized by alloantigen ELA-A5-restricted memory CTL (CTLm) from carrier horses; (2) to induce CTLm in horses with a retroviral vector expressing conserved CTL epitopes; (3) to determine whether or not co- expression of equine IL-12 and CTL epitopes by a retroviral vector will increase the frequency of CTLm; and (4) to determine whether or not immunized horses expressing at least one ELA-A5 allele are protected from or more efficiently control EIAV infection and disease following virus challenge.