Effects of Virus Load in the Pathogenesis of Lentivirus-Induced Lymphoid Interstitial Pneumonia

Abstract

To better define the relationship between ovine lentivirus (OvLV) infection and respiratory disease, pulmonary leukocytes and postmortem lung specimens from 42 sheep seropositive or at risk for OvLV infection were obtained. The lungs were examined for lesions of lymphoid interstitial pneumonia (LIP), and animals were categorized into five groups by severity of LIP and OvLV serologic status. The presence of OvLV in alveolar macrophages was established by proviral DNA amplification using the polymerase chain reaction (PCR), and the proportion of infected cells was determined by a quantitative focal immunoassay (FIA) and by immunohistochemistry. The concentration of OvLV p25 in serum was measured by capture ELISA. In contrast to animals with mild or no pulmonary lesions, sheep with moderate or severe LIP (17/42) were all seropositive, 71% had antigenemia (greater than 2 ng/mL), and 82% had proviral DNA in 1.5 x 10(5) alveolar macrophages. Of sheep positive by PCR, those with moderate or severe LIP (79%) had an average of 3 infected cells/10(3) alveolar macrophages by FIA. These results implicate alveolar macrophages as important target cells in the pathogenesis of OvLV-induced respiratory diseases.

Ovine Progressive Pneumonia Virus Capsid Antigen as Found in CD163- and CD172a-Positive Alveolar Macrophages of Persistently Infected Sheep

“…Links have been made between the presence of provirus in the lung of naturally OPPV-infected sheep or the amount of provirus in tissues and peripheral blood mononuclear cells of experimentally CAEV-infected goats and the degree of histological lesions in tissues. 7,13,48 Furthermore, a statistically significant correlation was observed between the amount of provirus in lung alveolar macrophages and adherent peripheral blood mononuclear cells of naturally infected sheep and the degree of histological lung lesions. 55 More recently, we showed that peripheral blood leukocyte ovine progressive pneumonia provirus levels correlate significantly with histological lesion scores in any of the affected tissues.…”

Development and Validation of an Ovine Progressive Pneumonia Virus Quantitative PCR

“…Subsequent reanalysis of the data from an earlier pathogenesis study showed that the presence of lung lesions (mild, moderate, or severe) correlates significantly with the presence of provirus in alveolar macrophages using PCR specific for ltr and pol (Fisher's exact test, two-sided P value ϭ 0.0003) (4). In addition, sheep with lung lesions had Ͼ10-fold more pol copies in their alveolar macrophages, determined by a quantitative PCR (qPCR), than sheep without lung lesions (27).…”

“…OPPV provirus is found in cells of the macrophage and monocyte lineage without causing cellular ablation (13,14). Specifically, OPPV provirus has been detected in many cell types, including lung type I and II pneumocytes, interstitial and alveolar macrophages, endothelial cells, fibroblasts, colostrum cells, cumulus cells, peripheral blood mononuclear cells, and peripheral blood leukocytes (PBL) (2,4,6,8,11,17,18,27). Plasma viremias are thought to be low in OPPV-infected sheep (3); therefore, measuring OPPV provirus loads may be the best way to quantitate virus in vivo.…”

Immune Response to Individual Maedi-Visna VirusgagAntigens

“…Other organ-specific changes, such as smooth muscle hyperplasia in the lung or demyelination in the central nervous system, also occur (6). Virus is usually cell associated, with only low frequencies of infected cells being detected even in lesions that are well developed (8,35,47). How the virus persists has been under investigation for many years with both latent or restricted infection and infection of myeloid precursors put forward as strategies which may aid the virus to survive in the host (19,20,44).…”