Wild-type equine infectious anemia virus replicates in vivo predominantly in tissue macrophages, not in peripheral blood monocytes

Abstract

In situ hybridization of tissues from two horses infected with the wild-type Wyoming strain of equine infectious anemia virus (EIAV) identified the liver, spleen, lymph nodes, kidney, lung, and adrenal gland as the primary host tissue sites for viral transcription during acute infection. Combined immunohistochemistry, with a monoclonal antibody recognizing a cytoplasmic antigen of equine mononuclear phagocytes, and in situ hybridization for viral RNA identified most infected cells as mature tissue macrophages. In contrast, in situ hybridization of adherent peripheral blood mononuclear cells collected from horses on various days during the first 2 weeks postinfection with the Wyoming strain of EIAV failed to detect any viral RNA in these cells. For the two horses described here, serum reverse transcriptase activity correlated directly with the degree of replication detected in tissue macrophages on the day of sacrifice. These results suggest that unlike other lentivirus infections in which mature tissue macrophages accumulate cytoplasmic viral RNA to a high level but fail to produce infectious virions, mature tissue macrophages are the likely primary source of the high titer of viremia present during acute infection with EIAV. No significant posttranscriptional block of viral replication in tissue macrophages appears to occur with EIAV.

The immunopathogenesis of equine infectious anemia virus

“…In situ hybridization of tissues from horses infected with the wild-type Wyoming strain of EIAV identified the liver, spleen, lymph nodes, kidney, lung, and adrenal gland as the primary host tissue sites for active viral transcription during acute infection, (Sellon et al, 1992) Combined immunohistochemistry, with a monoclonal antibody recognizing a cytoplasmic antigen of equine mononuclear phagocytes, and in situ hybridization for viral RNA identified most infected cells as mature tissue macrophages. In contrast, in situ hybridization of adherent peripheral blood mononuclear cells collected from horses on various days during the first two weeks postinfection failed to detect any viral RNA in these cells (Sellon et al, 1992). These results suggest that mature tissue macrophages are the primary source of the high titer of viremia present during acute infection with EIAV.…”

Equine Infectious Anemia Virus Entry Occurs through Clathrin-Mediated Endocytosis

“…Although the disease that EIAV causes was initially characterized more than 150 years ago, little is known about its mechanism of entry. In vivo, EIAV is primarily if not exclusively macrophage tropic; however, in tissue culture the virus is able to adapt to infect additional cell types, including endothelial cells and fibroblasts, from not only equine species but also from feline and canine origins as well (51,61). Changes within the long terminal repeat and envelope are associated with both altered virulence and cell tropism (13,41,55).…”

Equine Infectious Anemia

“…88 The majority of viral replication during a febrile episode appears to occur in mature tissue macrophages of these tissues, not in circulating blood monocytes. 88 Most horses spontaneously recover from the initial viremic episode over a period of several days, appear clinically normal for a variable period of time (days to weeks), and then experience recurring episodes of fever, thrombocytopenia, and depression!4 Each febrile episode is associated with viremia that resolves coincident with resolution of fever. Between febrile episodes, circulating virus is highly cell-associated and not free in plasma.…”