title: Bovine herpesvirus 1 can infect CD4(+) T lymphocytes and induce programmed cell death during acute infection of cattle.
abstract: Acute infection of cattle with bovine herpesvirus 1 (BHV-1) represses cell-mediated immunity, which can lead to secondary bacterial infections. Since BHV-1 can induce apoptosis of cultured lymphocytes, we hypothesized that these virus-host interactions occur in cattle. To test this hypothesis, we analyzed lymph nodes and peripheral blood mononuclear cells (PBMC) after calves were infected with BHV-1. In situ terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) staining of lymphoid tissues (pharyngeal tonsil, cervical, retropharyngeal, and inguinal) was used to detect apoptotic cells. Calves infected with BHV-1 for 7 days revealed increased apoptotic cells near the corticomedullary junction in lymphoid follicles and in the subcapsular region. Increased frequency of apoptotic cells was also observed in the mucosa-associated lymphoid tissue lining the trachea and turbinate. Immunohistochemistry of consecutive sections from pharyngeal tonsil revealed that CD2(+) T lymphocytes were positive for the BHV-1 envelope glycoprotein gD. The location of these CD2(+) T lymphocytes in the germinal center suggested that they were CD4(+) T cells. Electron microscopy and TUNEL also revealed apoptotic and herpesvirus-infected lymphocytes from this area. Fluorescence-activated cell sorting analyses demonstrated that CD4(+) and CD8(+) T cells decreased in lymph nodes and PBMC after infection. The decrease in CD4(+) T cells correlated with an increase in apoptosis. CD4(+) but not CD8(+) lymphocytes were infected by BHV-1 as judged by in situ hybridization and PCR, respectively. Immediate-early (bovine ICP0) and early (ribonucleotide reductase) transcripts were detected in PBMC and CD4(+) lymphocytes prepared from infected calves. In contrast, a late transcript (glycoprotein C) was not consistently detected suggesting productive infection was not efficient. Taken together, these results indicate that BHV-1 can infect CD4(+) T cells in cattle, leading to apoptosis and suppression of cell-mediated immunity.
authors.affiliation: Department of Veterinary and Biomedical Sciences, Center for Biotechnology, University of Nebraska, Lincoln, Lincoln, Nebraska 68583-0905, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Winkler
authors.forename: A
authors.initials: A
authors.lastname: Doster
authors.forename: C
authors.initials: C
authors.lastname: Jones
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure / Q000821:virology*; D002417:Cattle; D006566:Herpesviridae Infections / Q000276:immunology / Q000473:pathology*; D007242:Herpesvirus 1, Bovine; D007111:Immunity, Cellular; D020287:In Situ Nick-End Labeling; D008854:Microscopy, Electron