Immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus

Persistent infection of equids by equine infectious anemia virus (EIAV) is typically characterized by a progression during the first year postinfectio n from chronic disease with recurring disease cycles to a long-term asympto matic infection that is maintained indefinitely, The goal of the current st udy was to perform a comprehensive longitudinal analysis of the course of v irus infection and development of host immunity in experimentally infected horses as they progressed from chronic disease to long-term inapparent carr iage, We previously described the evolution of EIAV genomic quasispecies (C . Leroux, C. J. Issel, and R. C. Montelaro, J, Virol, 71:9627-9639, 1997) a nd 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 experi mentally infected ponies during sequential disease episodes associated with chronic disease during the first 10 months postinfection. In the current s tudy, we extended the studies of these experimentally infected ponies to 3 years postinfection to characterize the levels of virus replication and dev elopment of host immune responses associated with the progression from chro nic 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 w ith the severity of chronic disease, indicating different levels of control of virus replication during long-term inapparent infections. Detailed anal yses of antibody and cellular immune responses in all four ponies over the 3-year course of infection revealed a similar evolution during the first ye ar postinfection of robust humoral and cellular immunity that then remained relatively constant during long-term inapparent infection. These observati ons indicate that immune parameters that have previously been correlated wi th EIAV vaccine protection fail to provide reliable Immune correlates of co ntrol of virus replication or clinical outcome in experimental infections. Thus, these data emphasize the differences between immunity to virus exposu re and immune control of an established viral infection and further emphasi ze the need to develop and evaluate novel immunoassays to define reliable i mmune correlates to vaccine and infection immunity, respectively.