Genome sequence and experimental infection of calves with bovine gammaherpesvirus 4 (BoHV-4)

Authors: BAUEMANN, FENANDO - Oklahoma State University; Falkenberg, Shollie; MARTINS, MATHAIS - South Dakota State University; Dassanayake, Rohana; Neill, John; RIDPATH, JULIA - Retired ARS Employee; SILVERIA, SIMONE - Federal University Of Rio Grande Do Sul; PALMER, MITCHELL - Retired ARS Employee; BUYSSE, A - South Dakota State University; MOHR, A - South Dakota State University; FLORES, EDUARDO - Universidade Federal De Santa Maria; DIEL, DIEGO - South Dakota State University

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/24/2022
Publication Date: 6/16/2022
Citation: Bauemann, F.V., Falkenberg, S.M., Martins, M., Dassanayake, R.P., Neill, J.D., Ridpath, J.F., Silveria, S., Palmer, M., Buysse, A., Mohr, A., Flores, E., Diel, D. 2022. Genome sequence and experimental infection of calves with bovine gammaherpesvirus 4 (BoHV-4). Journal of General Virology. 167(8):1659-1668. https://doi.org/10.1007/s00705-022-05486-8.
DOI: https://doi.org/10.1007/s00705-022-05486-8

Interpretive Summary: Bovine herpesvirus-4 (BoHV-4) has been mostly thought of as a reproductive pathogen in cattle, but recently an increase in the number of positive respiratory samples has been observed at the South Dakota State Diagnostic lab. The increase in positive respiratory samples has prompted concerns that there have been changes in the more contemporary viral isolates currently circulating in cattle. Therefore, the current study evaluated the pathogenesis of current contemporary BoHV-4 isolates and observed their disease progression and pathology in the respiratory tissues. BoHV-4 virus was detected in the tonsil and lymph nodes in the first 10 days after exposure to the virus. Virus was also detected in the respiratory tract, regional lymphoid tissues, and trigeminal ganglia of calves euthanized on day 35 post exposure. Furthermore, virus was observed to be fluorescently labeled in nerve bundles surrounding the trigeminal ganglia and retropharyngeal lymph nodes on tissues from calves euthanized on day 35 post-exposure. This study contributes to the understanding of the infection dynamics and tissue distribution of BoHV-4 following IN infection calves using more contemporary isolates. Despite the increased detection of BoHV-4 in clinical samples in the US, results from this study would suggest that the two contemporary isolates used in our study are not pathogenic to calves after intranasal inoculation.

Technical Abstract: Bovine gammaherpesvirus 4 (BoHV-4) is ubiquitous in cattle worldwide and it has been detected in animals exhibiting broad clinical presentations. The virus has been detected in the United States since the 70’s, however, its clinical relevance remains unknown. Here we determined the complete genome sequence of two contemporary BoHV-4 isolates and assessed clinical, virological and pathological outcomes upon intranasal (IN) inoculation in calves. A slight and transient increase in body temperature was the only clinical sign observed in BoHV-4-inoculated calves. Additionally, short-term and transient viremia and virus shedding in nasal secretions were observed in all inoculated calves. No histological changes were observed in the respiratory tract (turbinate, trachea and lung), lymphoid tissues (tonsil, lymph nodes, thymus and spleen), or central nervous tissues (olfactory bulb and trigeminal ganglia) sampled throughout the animal studies (days 5, 10 and 35 post-inoculation [pi]). However, BoHV-4 DNA was detected by nested-PCR and in situ hybridization (ISH) in the tonsil and regional lymph nodes of calves euthanized on day 5 pi and in the lungs of calves euthanized on day 10 pi. Calves euthanized on day 35 pi harbored BoHV-4 DNA in the respiratory tract (turbinates, trachea, lungs), regional lymphoid tissues and trigeminal ganglia. Interestingly, ISH revealed the presence of BoHV-4 DNA in nerve bundles surrounding the trigeminal ganglia and retropharyngeal lymph nodes (day 35 pi). This study contributes to the understanding of the infection dynamics (viremia and virus shedding) and tissue distribution of BoHV-4 following IN infection in calves. Notably, despite the increased detection of BoHV-4 in clinical samples in the US, results here suggest that the two contemporary isolates used in our study are not pathogenic to calves after intranasal inoculation.