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 1970s; however, its clinical relevance remains unknown. Here, we determined the complete genome sequences of two contemporary BoHV-4 isolates obtained from respiratory (SD16-38) or reproductive (SD16-49) tract specimens and assessed clinical, virological, and pathological outcomes upon intranasal (IN) inoculation of calves with the respiratory BoHV-4 isolate SD16-38. A slight and transient increase in body temperature was observed in BoHV-4-inoculated calves. Additionally, transient viremia and virus shedding in nasal secretions were observed in all inoculated calves. BoHV-4 DNA was detected by nested PCR in the tonsil and regional lymph nodes (LNs) of calves euthanized on day 5 post-inoculation (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, in situ hybridization revealed the presence of BoHV-4 DNA in nerve bundles surrounding the trigeminal ganglia and retropharyngeal lymph nodes (day 35 pi). No histological changes were observed in the respiratory tract (turbinate, trachea, and lung), lymphoid tissues (tonsil, LNs, thymus, and spleen), or central nervous tissues (olfactory bulb and trigeminal ganglia) sampled throughout the animal studies (days 5, 10, and 35 pi). This study contributes to the understanding of the infection dynamics and tissue distribution of BoHV-4 following IN infection in calves. These results suggest that BoHV-4 SD16-38 used in our study has low pathogenicity in calves upon intranasal inoculation.
Similar content being viewed by others
Data availability
The complete genome sequences generated in this study can be found in the GenBank database under accession numbers MN551083 and MN551084.
References
Wellenberg GJ, Van Der Poel WHM, Van Der Vorst TJK et al (2000) Bovine herpesvirus 4 in bovine clinical mastitis. Vet Rec. https://doi.org/10.1136/vr.147.8.222
Czaplicki G, Thiry E (1998) An association exists between bovine herpesvirus-4 seropositivity and abortion in cows. Prev Vet Med 33:235–240. https://doi.org/10.1016/S0167-5877(97)00036-6
Chastant-Maillard S (2015) Impact of bovine herpesvirus 4 (BoHV-4) on reproduction. Transbound Emerg Dis 62:245–251. https://doi.org/10.1111/tbed.12155
Deim Z, Szeredi L, Tompó V, Egyed L (2006) Detection of bovine herpesvirus 4 in aborted bovine placentas. Microb Pathog 41:144–148. https://doi.org/10.1016/j.micpath.2006.03.006
Egyed L, Sassi G, Tibold J et al (2011) Symptomless intrauterine transmission of bovine herpesvirus 4 to bovine fetuses. Microb Pathog 50:322–325. https://doi.org/10.1016/j.micpath.2010.10.006
Bartha A, Juhasz M, Liebermann H (1966) Isolation of a bovine herpesvirus from calves with respiratory disease and keratoconjunctivitis. A preliminary report. Acta Vet Acad Sci Hung 16:357–358
Gagnon CA, Traesel CK, Music N et al (2017) Whole genome sequencing of a Canadian bovine gammaherpesvirus 4 strain and the possible link between the viral infection and respiratory and reproductive clinical manifestations in dairy cattle. Front Vet Sci 4:92. https://doi.org/10.3389/fvets.2017.00092
Mohanty SB, Hammond RC, Lillie MG (1971) A new bovine herpesvirus and its effect on experimentally infected calves. Brief report. Arch Gesamte Virusforsch 33:394–395
Rossiter PB, Gumm ID, Stagg DA et al (1989) Isolation of bovine herpesvirus-3 from African buffaloes (Syncerus caffer). Res Vet Sci 46:337–343
Moreno-Lopez J, Goltz M, Rehbinder C et al (1989) A bovine herpesvirus (BHV-4) as passenger virus in ethmoidal tumours in Indian cattle. Zentralbl Veterinarmed B 36:481–486
Ehlers B, Buhk HJ, Ludwig H (1985) Analysis of bovine cytomegalovirus genome structure: cloning and mapping of the monomeric polyrepetitive DNA unit, and comparison of European and American strains. J Gen Virol 66(Pt 1):55–68. https://doi.org/10.1099/0022-1317-66-1-55
Kit S, Kit M, Ichimura H et al (1986) Induction of thymidine kinase activity by viruses with group B DNA genomes: bovine cytomegalovirus (bovine herpesvirus 4). Virus Res 4:197–212
ICTV (2018) Virus Taxonomy: 2018 Release. Washington, DC
Zimmermann W, Broll H, Ehlers B et al (2001) Genome sequence of bovine herpesvirus 4, a bovine Rhadinovirus, and identification of an origin of DNA replication. J Virol 75:1186–1194. https://doi.org/10.1128/JVI.75.3.1186-1194.2001
Thiry E, Bublot M, Dubuisson J et al (1992) Molecular biology of bovine herpesvirus type 4. Vet Microbiol 33:79–92. https://doi.org/10.1016/0378-1135(92)90037-T
Verna AE, Manrique JM, Pérez SE et al (2012) Genomic analysis of bovine herpesvirus type 4 (BoHV-4) from Argentina: High genetic variability and novel phylogenetic groups. Vet Microbiol 160:1–8. https://doi.org/10.1016/j.vetmic.2012.04.039
Dewals B, Thirion M, Markine-Goriaynoff N et al (2006) Evolution of Bovine herpesvirus 4: recombination and transmission between African buffalo and cattle. J Gen Virol 87:1509–1519. https://doi.org/10.1099/vir.0.81757-0
Wellenberg GJ, Bruschke CJM, Wisselink HJ et al (2002) Simultaneous intramammary and intranasal inoculation of lactating cows with bovine herpesvirus 4 induce subclinical mastitis. Vet Microbiol 86:115–129. https://doi.org/10.1016/S0378-1135(01)00496-5
Thiry E, Dubuisson J, Bublot M et al (1990) The biology of bovine herpesvirus-4 infection of cattle. Dtsch Tierarztl Wochenschr 97:72–77
Egyed L, Ballagi-Pordány A, Bartha A, Belák S (1996) Studies of in vivo distribution of bovine herpesvirus type 4 in the natural host. J Clin Microbiol 35:1091–1095
Egyed L (2000) Bovine herpesvirus type 4: a special herpesvirus (review article). Acta Vet Hung 48:501–513. https://doi.org/10.1556/004.48.2000.4.13
Dubuisson J, Thiry E, Bublot M et al (1989) Experimental infection of bulls with a genital isolate of bovine herpesvirus-4 and reactivation of latent virus with dexamethasone. Vet Microbiol 21:97–114
Osorio FA, Rock DL, Reed DE (1985) Studies on the pathogenesis of a bovine cytomegalo-like virus in an experimental host. J Gen Virol 66:1941–1951. https://doi.org/10.1099/0022-1317-66-9-1941
Egyed L, Bartha A (1998) PCR studies on the potential sites for latency of BHV-4 in calves. Vet Res Commun 22:209–216
Osorio FA, Reed DE (1983) Experimental inoculation of cattle with bovine herpesvirus-4: evidence for a lymphoid-associated persistent infection. Am J Vet Res 44:975–980
Castrucci G, Frigeri F, Ferrari M et al (1987) Experimental infection of calves with strains of Bovid herpesvirus-4. Comp Immunol Microbiol Infect Dis. https://doi.org/10.1016/0147-9571(87)90039-7
Castrucci G, Frigeri F, Ferrari M, et al (1987) Reactivation in calves of latent infection by Bovid herpesvirus-4. Microbiologica
Boisvert S, Raymond F, Godzaridis É et al (2012) Ray Meta: scalable de novo metagenome assembly and profiling. Genome Biol 13:R122. https://doi.org/10.1186/gb-2012-13-12-r122
Myers EW (2000) A whole-genome assembly of Drosophila. Science (80-) 287:2196–2204. https://doi.org/10.1126/science.287.5461.2196
Huang X, Madan A (1999) CAP3: a DNA sequence assembly program. Genome Res 9:868–877. https://doi.org/10.1101/gr.9.9.868
Falkenberg SM, Ridpath J, Vander Ley B et al (2014) Comparison of temperature fluctuations at multiple anatomical locations in cattle during exposure to bovine viral diarrhea virus. Livest Sci 164:159–167. https://doi.org/10.1016/j.livsci.2014.03.018
Storz J (1968) Comments on malignant catarrhal fever. J Am Vet Med Assoc 152:804–806
Areda D, Chigerwe M, Crossley B (2018) Bovine herpes virus type-4 infection among postpartum dairy cows in California: risk factors and phylogenetic analysis. Epidemiol Infect 146:904–912. https://doi.org/10.1017/S0950268818000791
Morán P, Pérez S, Odeón A, Verna A (2019) Comparative analysis of replicative properties of phylogenetically divergent, Argentinean BoHV-4 strains in cell lines from different origins. Comp Immunol Microbiol Infect Dis 63:97–103. https://doi.org/10.1016/J.CIMID.2019.01.014
Delooz L, Czaplicki G, Houtain JY et al (2017) Laboratory findings suggesting an association between BoHV-4 and bovine abortions in Southern Belgium. Transbound Emerg Dis 64:1100–1109. https://doi.org/10.1111/tbed.12469
Szenci O, Sassi G, Fodor L et al (2016) Co-infection with Bovine Herpesvirus 4 and Histophilus somni significantly extends the service period in dairy cattle with purulent vaginal discharge. Reprod Domest Anim 51:143–149. https://doi.org/10.1111/RDA.12658
Homan EJ, Easterday BC (1981) Further studies of naturally occurring latent bovine herpesvirus infection. Am J Vet Res 42:1811–1813
Campos FS, Franco AC, Oliveira MT et al (2014) Detection of bovine herpesvirus 2 and bovine herpesvirus 4 DNA in trigeminal ganglia of naturally infected cattle by polymerase chain reaction. Vet Microbiol 171:182–188. https://doi.org/10.1016/J.VETMIC.2014.03.012
Romeo F, Spetter MJ, Moran P et al (2019) Analysis of the transcripts encoding for antigenic proteins of bovine gammaherpesvirus 4. J Vet Sci. https://doi.org/10.4142/JVS.2020.21.E5
Machiels B, Stevenson PG, Vanderplasschen A, Gillet L (2013) A gammaherpesvirus uses alternative splicing to regulate its tropism and its sensitivity to neutralization. PLOS Pathog 9:e1003753. https://doi.org/10.1371/JOURNAL.PPAT.1003753
Williams LBA, Fry LM, Herndon DR et al (2019) A recombinant bovine herpesvirus-4 vectored vaccine delivered via intranasal nebulization elicits viral neutralizing antibody titers in cattle. PLoS ONE 14:e0215605. https://doi.org/10.1371/journal.pone.0215605
Acknowledgments
The authors would like to thank the NADC animal facility staff and animal caretakers for the care and handling of the animals.
Funding
This work was supported by the United States Department of Agriculture (USDA) National Institute of Food and Agriculture, Hatch Projects (SD00H517-14 and NYC-2020-21-229) and AFRI Foundational and Applied Science Program (grant no. 2017-67015-32034/project accession no. NYCV478904). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the NIFA or the USDA.
Author information
Authors and Affiliations
Contributions
Conceived the study: SFM, EFF, DGD. Tested experimental samples: FVB, SMF, MM, RPD, SS, MVP, AB, AM. Data analysis and result interpretation: FVB, SMF, MM, JDN, JFR, MVP, EFF, DGD. Manuscript writing: FVB, SMF, MM, EFF, DGD. All authors have reviewed and edited the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Ethical approval
All animals were handled in accordance with the Animal Welfare Act Amendments (7 U.S. Code §2131 to §2156), and all study procedures were reviewed and approved by the Institutional Animal Care and Use Committee at the National Animal Disease Center (ARS-2016-572) or by the Ethical Committee at UFSM (CEUA/UFSM protocol number 034/2014).
Additional information
Handling Editor: Ana Cristina Bratanich.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Bauermann, F.V., Falkenberg, S.M., Martins, M. et al. Genome sequence and experimental infection of calves with bovine gammaherpesvirus 4 (BoHV-4). Arch Virol 167, 1659–1668 (2022). https://doi.org/10.1007/s00705-022-05486-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00705-022-05486-8