Bovine herpesvirus-1 infects activated CD4+ lymphocytes.
Acute virus infections can induce immune deficiencies, as shown by immunosuppression to a variety of antigens and mitogens. Previously we observed that live bovine herpesvirus-1 (BHV-1) induced considerable lymphocyte death in culture, suggesting that the virus infected one or more cell populations. Our goal was to identify the cells infected by BHV-1 and the mechanism resulting in cell death. ConA activated cells were cultured with BHV-1 and stained with monoclonal antibodies specific for virus envelope glycoproteins (gB, gC and gD) and lymphocyte surface proteins (CD2, CD4 and CD8) and a molecule associated with gamma/delta cells. Two-colour immunofluorescence revealed that virus glycoproteins were preferentially expressed on T lymphocytes of the CD4+ phenotype. Live virus was required for virus glycoprotein expression, and by 48 h considerable loss of CD4 expression was observed. To confirm virus replication, RNA was isolated from cells, reverse transcribed and amplified using primers to a 342 bp region of immediate-early and early genes (IER2.9/ER2.6) or a 392 bp region of an early gene (gD). Immediate-early/early gene products were detected in CD4+T lymphocytes but not in infectious virions. Lymphocyte apoptosis was observed by 7 h post-infection with increasing levels of cell death at 24-48 h after infection. These findings suggest that the loss of proliferating CD4+ T cells during infection or vaccination with modified live vaccines provides the opportunity for secondary infections that commonly occur following BHV-1 infection.
Eskra
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Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison 53706, USA.
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D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D002417:Cattle; D002478:Cells, Cultured; D003208:Concanavalin A; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D007242:Herpesvirus 1, Bovine / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D017874:Immediate-Early Proteins / Q000032:analysis / Q000235:genetics; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis; D014759:Viral Envelope Proteins / Q000032:analysis; D014779:Virus Replication / Q000276:immunology
D015703:Antigens, CD; D017874:Immediate-Early Proteins; D012367:RNA, Viral; D014759:Viral Envelope Proteins; D003208:Concanavalin A