Immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus
Immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus
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DOI：
10.1128/jvi.74.13.5968-5981.2000
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发表时间：
2000-07-01
影响因子：
5.4
通讯作者：
Montelaro, RC
中科院分区：
文献类型：
--
作者：
Hammond, SA;Li, F;Montelaro, RC
马传染性贫血病毒(EIAV)持续感染马的特征是在感染后第一年内从慢性疾病和反复发作的疾病周期发展到长期无症状感染，并保持无限期。本研究的目标是对实验感染的马从慢性病进展到长期隐性携带的病毒感染过程和宿主免疫的发展进行全面的纵向分析。我们先前描述了EIAV基因组准种的进化(C.Leroux，C.J.Issel和R.C.Montelaro，J，Virol，71：9627-9639，)和宿主免疫反应(S.A.哈蒙德，S.J.库克，D.L.利希滕斯坦，C.J.，Issel，和RC，Montelaro，J.Virol，71：3840-3852,1997)，在感染后10个月内与慢性疾病相关的连续疾病发作中。在目前的研究中，我们将这些实验感染的小马的研究扩展到感染后3年，以表征病毒复制水平和宿主免疫反应的发展与从慢性病到长期隐性感染的进展相关。这些研究的结果显示，在长期隐性感染期间检测到的血浆病毒RNA稳态水平与慢性疾病的严重程度相关，差异超过10(3)倍，表明在长期隐性感染期间对病毒复制的控制程度不同。对所有四匹小马3年感染过程中的抗体和细胞免疫反应的详细分析显示，在感染后的第一年，强劲的体液和细胞免疫发生了类似的演变，然后在长期隐性感染期间保持相对稳定。这些观察表明，以前与EIAV疫苗保护相关的免疫参数未能为控制病毒复制或实验性感染的临床结果提供可靠的免疫相关性。因此，这些数据强调了对病毒暴露的免疫和对已建立的病毒感染的免疫控制之间的差异，并进一步强调了开发和评估新的免疫分析方法的必要性，以确定分别与疫苗和感染免疫有关的可靠的免疫相关性。
Persistent infection of equids by equine infectious anemia virus (EIAV) is typically characterized by a progression during the first year postinfection from chronic disease with recurring disease cycles to a long-term asymptomatic infection that is maintained indefinitely, The goal of the current study was to perform a comprehensive longitudinal analysis of the course of virus infection and development of host immunity in experimentally infected horses as they progressed from chronic disease to long-term inapparent carriage, We previously described the evolution of EIAV genomic quasispecies (C. Leroux, C. J. Issel, and R. C. Montelaro, J, Virol, 71:9627-9639, 1997) and host immune responses (S. A. Hammond, S. J. Cook, D. L. Lichtenstein, C. J, Issel, and R C, Montelaro, J. Virol, 71:3840-3852, 1997) in four experimentally infected ponies during sequential disease episodes associated with chronic disease during the first 10 months postinfection. In the current study, we extended the studies of these experimentally infected ponies to 3 years postinfection to characterize the levels of virus replication and development of host immune responses associated with the progression from chronic disease to long-term inapparent infection. The results of these studies revealed over a 10(3)-fold difference in the steady-state levels of plasma viral RNA detected during long-term inapparent infection that correlated with the severity of chronic disease, indicating different levels of control of virus replication during long-term inapparent infections. Detailed analyses of antibody and cellular immune responses in all four ponies over the 3-year course of infection revealed a similar evolution during the first year postinfection of robust humoral and cellular immunity that then remained relatively constant during long-term inapparent infection. These observations indicate that immune parameters that have previously been correlated with EIAV vaccine protection fail to provide reliable Immune correlates of control of virus replication or clinical outcome in experimental infections. Thus, these data emphasize the differences between immunity to virus exposure and immune control of an established viral infection and further emphasize the need to develop and evaluate novel immunoassays to define reliable immune correlates to vaccine and infection immunity, respectively.