Tissue Sites of Persistent Infection and Active Replication of Equine Infectious Anemia Virus during Acute Disease and Asymptomatic Infection in Experimentally Infected Equids

Abstract

Equine infectious anemia virus (EIAV) infection of horses is characterized by recurring cycles of disease and viremia that typically progress to an inapparent infection in which clinicalEquine infectious anemia virus (EIAV) is unique among lentiviruses in that the clinical course of infection in equids results initially in a rapid and dynamic series of clearly demarcated cycles of disease and associated viremia that begin by 3 weeks postinfection and continue at irregular intervals separated by weeks or months (reviewed in reference 25). Disease cycles last 3 to 5 days and are characterized by fever, diarrhea, lethargy, edema, anemia, and thrombocytopenia. This stage of disease, defined as chronic equine infectious anemia (EIA), typically lasts about 8 to 12 months postinfection, with the frequency and severity of clinical episodes decreasing with time. In contrast to the progressive degenerative disease associated with most lentiviral infections, horses infected with EIAV typically make a transition during the first year postinfection from chronic EIA to an inapparent infection in which clinical symptoms are absent and viremia is usually undetectable for the remainder of the animal's life span of up to about 20 years. Thus, the EIAV systems provides a novel model in which to examine the dynamics of lentivirus replication during clearly defined cycles of disease and during long-term asymptomatic infections.Several lines of evidence indicate that the control of EIAV replication and disease in long-term inapparent carriers is mediated by virus-specific host immune responses that evolve during the first year postinfection to achieve an enduring effective suppression of virus replication. For example, experimental infection of foals with severe combined immunodeficiency results in a progressive infection leading to death, demonstrating the necessity of the host immune system in accomplishing the temporal control of virus replication associated with infection of immunocompetent horses (29). In addition, it has been shown that severe stress or treatment of long-term inapparent carriers with immunosuppressive drugs can cause recrudescence of viremia and disease, even after decades of clinical quiescence (16,48). Finally, it has been demonstrated that transfer of whole blood from long-term inapparent carriers to naive horses results in EIAV infection and disease in the recipient horses (12). Taken together, these observations demonstrate the lack of attenuation of the infect-* Corresponding author. Mailing address:

Equine Infectious Anemia Virus (EIAV): what has HIV?s country cousin got to tell us?

“…3). The sequences of clinical events, establishment of immune response and virus evolution have been well documented in horses and ponies (Equus caballus) [54,55,83,124,155]. Clinical, serological and virological responses after experimental infection of donkeys (Equus asinus) and detection of virus and description of the disease in mules (Equus caballus × Equus asinus) have been reported [30,161].…”

“…As we mentioned previously, viral replication is efficiently reduced to a subclinical level in animals evolving from the chronic stage to the asymptomatic stage of EIAV infection. In long-term inapparent EIAV-carriers, a low level of virus infection and replication can be detected in tissue macrophages [55,124] and associated with plasma viremia [54,83]. The importance of the immune response in this control was rapidly indicated by experimental immune suppression in asymptomatic animals leading to the recrudescence of disease symptoms, even after several decades of infection [79,177].…”

Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines

“…EIA is characterized during its acute and chronic stages by defined episodes of clinical disease triggered by waves of viremia and distinguished by fever, anemia, thrombocytopenia, edema, and various wasting signs. By 8-12 months post-infection horses typically progress to life-long inapparent carriers, but continue to harbor various steady state levels of viral replication in monocyte-rich tissue reservoirs [15][16][17]. Stress or immune suppression of EIAV inapparent carriers can induce an increase in viral replication and potentially a recrudescence of disease [17,18].…”

Envelope variation as a primary determinant of lentiviral vaccine efficacy

“…The acute and chronic stages are defined by episodes of clinical disease, triggered by waves of viremia, and distinguished by fever, anemia, thrombocytopenia, edema, and various wasting signs. By 1 year after infection, animals typically progress to life-long inapparent carriers, continuing to harbor steady-state levels of viral replication in monocyte-rich tissue reservoirs (19)(20)(21). Stress or immune suppression of inapparent carriers can induce increases in viral replication and, potentially, a recrudescence of disease (19,22).…”