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Bovine herpesvirus-1 infects activated CD4+ lymphocytes
1Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison 53706, USA.
Insights
Bovine herpesvirus-1 (BHV-1) infects and kills CD4+ T lymphocytes, leading to immune deficiency. This viral-induced T-cell loss during infection or vaccination may increase susceptibility to secondary infections.
Area of Science:
- Veterinary Virology
- Immunology
- Molecular Biology
Background:
- Acute viral infections can cause immune deficiencies.
- Bovine herpesvirus-1 (BHV-1) has been observed to cause lymphocyte death in cell cultures.
Purpose of the Study:
- To identify the specific cells infected by BHV-1.
- To elucidate the mechanism by which BHV-1 causes cell death.
Main Methods:
- Two-colour immunofluorescence staining for viral glycoproteins and lymphocyte surface proteins (CD4, CD8).
- Detection of viral gene expression using reverse transcription and PCR.
- Assessment of lymphocyte apoptosis via cell death assays.
Main Results:
- BHV-1 glycoproteins were predominantly expressed on CD4+ T lymphocytes.
- Viral replication was confirmed in CD4+ T lymphocytes.
- Significant lymphocyte apoptosis and CD4+ T-cell loss were observed post-infection.
Conclusions:
- BHV-1 preferentially infects and induces apoptosis in CD4+ T lymphocytes.
- The depletion of CD4+ T cells by BHV-1 may contribute to secondary infections.
- Understanding this mechanism is crucial for managing BHV-1 infections and vaccinations.
Abstract:
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.