Distribution and Cellular Heterogeneity of Bovine Viral Diarrhea Viral Antigen Expression in the Brain of Persistently Infected Calves: A New Perspective

Abstract

Persistent infection following in utero exposure to bovine viral diarrhea virus (BVDV) early in gestation is a serious cause of morbidity and mortality in cattle industries worldwide. The brain is a primary target of persistent infection. In the current study, the types of cells infected and topography of viral antigen expression were examined in brain sections from 9 BVDV persistently infected crossbred calves, all less than 1 year of age, by immunohistochemical staining using the 15C5 primary monoclonal antibody. BVDV antigen was detected in the brains of all persistently infected calves. A variety of cell types was infected, including neurons, astrocytes, oligodendroglia, blood vessel-associated cells (pericytes, perivascular macrophages, smooth muscle cells), and cells in the leptomeninges (blood vessel-associated cells). Conclusive demonstration of viral antigen in vascular endothelial cells was elusive. The intensity and distribution of viral antigen staining in neurons were highly variable. Viral antigen staining was most consistent and intense in thalamic nuclei, most notably in dorsal and medial nuclear groups, followed by the hippocampus, entorhinal cortex, basal nuclei, and piriform cortex. Staining in other brain areas was often less intense and inconsistent. The variability in the intensity and topography of viral antigen in the brain may explain the heterogeneity in the clinical manifestations of BVDV-induced disease. Additionally, infection of the brain in persistently infected calves may underlie or at least contribute to endocrine disturbances and immunologic deficits that are protean manifestations of BVDV-induced disease.

The Fetal Brain in Bovine Viral Diarrhea Virus-infected Calves: Lesions, Distribution, and Cellular Heterogeneity of Viral Antigen at 190 Days Gestation

“…7,14,23,39 Involvement of nuclei throughout most areas of the thalamus was pronounced and sharply contrasted with sections taken at the level of the basal nuclei, mesencephalon, and medulla oblongata. This pattern of relatively intense labeling in the thalamus is analogous to a recently reported study in postnatal persistently infected calves 23 but differs from earlier comprehensive reports.…”

“…7,14,23,39 In contrast, no viral antigen or lesions were detected in fetuses exposed to the virus at 175 days of gestation.…”

“…4, 23 Briefly, sections were deparaffinized and rehydrated. After pretreatment with proteinase K and an appropriate blocking step, sections were exposed to the primary antibody at a dilution of 1 : 1,000 using an automated immunostainer (DakoCytomation, Carpenteria, CA).…”

Distribution of Bovine Viral Diarrhoea Virus Antigen in Persistently Infected White-Tailed Deer (Odocoileus virginianus)

“…With the exception of the IHC on fawn 1, for which the monoclonal antibody (MAb) 15C5 (Syracuse Bioanalytical, East Syracuse, New York, USA) was utilized, MAb 3.12F1 (Oklahoma Animal Disease Diagnostic Laboratory, Stillwater, Oklahoma, USA) was used for detection of BVDV antigen. This MAb shows high agreement with MAb 15C5 that is used widely for IHC on ear-notch samples and has been utilized with samples from white-tailed deer (Montgomery, 2007;Passler et al, 2008). Following incubation with the primary antibody, BVDV antigen was detected using a biotinylated link antibody followed by peroxidaselabelled streptavidin (Dako).…”

“…Viral infection of reproductive and endocrine organs and immune system cells are implied to play a role in the pathogenesis of BVDV-associated diseases (Bielefeldt Ohmann, 1988;Grooms et al, 1996;Shin and Acland, 2001). The diversity of clinical signs observed in PI cattle has been implied to result from heterogeneous antigen distribution in the central nervous system (CNS) of affected animals (Montgomery, 2007).…”