[en] Alcelaphine herpesvirus 1 (AlHV-1) is a gammaherpesvirus carried asymptomatically by wildebeest. Upon cross-species transmission, AlHV-1 induces malignant catarrhal fever (MCF), a fatal lymphoproliferative disease of ruminants, including cattle. The strain C500 has been cloned as an infectious, pathogenic bacterial artificial chromosome (BAC) that is used to study MCF. Although AlHV-1 infection can be established in cell culture, multiple passages in vitro cause a loss of virulence associated with rearrangements of the viral genome. Here, sequencing of the BAC clone showed that the long unique region (LUR) of the genome is nearly identical to that of the previously sequenced strain from which the BAC was derived, and identified the duplication and translocation of a region from within LUR, containing the entire coding sequences of ORF50-encoding reactivation transactivator Rta and A6-encoding bZIP protein genes. The duplicated region was further located to a position within the terminal repeat (TR) and its deletion resulted in lower ORF50 expression levels and reduced viral fitness. Finally, the presence of a similar but not identical duplication and translocation containing both genes was found in AlHV-1 strain WC11. These results indicate that selection pressure for enhanced viral fitness may drive the duplication of ORF50 and A6 in AlHV-1.
Plowright, W. In Virus infections of ruminants (ed Morein, B., Dinter, Z. ) 123-150 (Elsevier, 1990).
Plowright, W., Ferris, R. D., Scott, G. R. Blue wildebeest and the aetiological agent of bovine malignant catarrhal fever. Nature 188,1167-1169 (1960).
Plowright, W. Malignant Catarrhal Fever in East Africa. I. Behaviour of the Virus in Free-Living Populations of Blue Wildebeest(Gorgon Taurinus Taurinus, Burchell). Res Vet Sci 6, 56-68 (1965).
Plowright, W. Malignant Catarrhal Fever in East Africa. II. Observations on Wildebeest Calves at the Laboratory and ContactTransmission of the Infection to Cattle. Res Vet Sci 6, 69-83 (1965).
Dewals, B., et al. L'herpèsvirus alcélaphin 1, l'agent responsable de la forme africaine du coryza gangreneux. Ann. Méd. Vét. 147,373-386 (2003).
Dewals, B., Boudry, C., Farnir, F., Drion, P. V., Vanderplasschen, A. Malignant catarrhal fever induced by alcelaphine herpesvirus1 is associated with proliferation of CD8 + T cells supporting a latent infection. PLoS One 3, e1627 (2008).
Dewals, B., et al. Ex vivo bioluminescence detection of alcelaphine herpesvirus 1 infection during malignant catarrhal fever. Journalof virology 85, 6941-6954 (2011).
Palmeira, L., et al. An essential role for gamma-herpesvirus latency-associated nuclear antigen homolog in an acutelymphoproliferative disease of cattle. Proceedings of the National Academy of Sciences of the United States of America 110, E1933-1942(2013).
Dewals, B. G., Vanderplasschen, A. Malignant catarrhal fever induced by Alcelaphine herpesvirus 1 is characterized by anexpansion of activated CD3 + CD8 + CD4-T cells expressing a cytotoxic phenotype in both lymphoid and non-lymphoid tissues. Vet Res 42, 95 (2011).
Bedelian, C., Nkedianye, D., Herrero, M. Maasai perception of the impact and incidence of malignant catarrhal fever (MCF) insouthern Kenya. Prev Vet Med 78, 296-316 (2007).
Cleaveland, S., Kusiluka, L., ole Kuway, J., Bell, C., Kazwala, R. Assessing the impact of malignant catarrhal fever in Ngorongorodistrict, Tanzania. (Community-based Animal Health and Participatory Epidemiology Unit (CAPE), OAU, 2001).
Wambua, L., Wambua, P. N., Ramogo, A. M., Mijele, D., Otiende, M. Y. Wildebeest-associated malignant catarrhal fever:perspectives for integrated control of a lymphoproliferative disease of cattle in sub-Saharan Africa. Arch Virol 161, 1-10 (2016).
Plowright, W., Herniman, K. A., Jessett, D. M., Kalunda, M., Rampton, C. S. Immunisation of cattle against the herpesvirus ofmalignant catarrhal fever: failure of inactivated culture vaccines with adjuvant. Res Vet Sci 19, 159-166 (1975).
Plowright, W., Macadam, R. F., Armstrong, J. A. Growth and Characterization of the Virus of Bovine Malignant Catarrhal Fever inEast Africa. J Gen Microbiol 39, 253-266 (1963).
Ensser, A., Pflanz, R., Fleckenstein, B. Primary structure of the alcelaphine herpesvirus 1 genome. Journal of virology 71, 6517-6525(1997).
Bridgen, A., Herring, A. J., Inglis, N. F., Reid, H. W. Preliminary characterization of the alcelaphine herpesvirus 1 genome. TheJournal of general virology 70 (Pt 5), 1141-1150 (1989).
Handley, J. A., Sargan, D. R., Herring, A. J., Reid, H. W. Identification of a region of the alcelaphine herpesvirus-1 genomeassociated with virulence for rabbits. Vet Microbiol 47, 167-181 (1995).
Wright, H., et al. Genome re-arrangements associated with loss of pathogenicity of the-herpesvirus alcelaphine herpesvirus-1. Research in Veterinary Science 75, 163-168 (2003).
Staudt, M. R., Dittmer, D. P. The Rta/Orf50 transactivator proteins of the gamma-herpesviridae. Curr Top Microbiol Immunol 312,71-100 (2007).
Coulter, L. J., Wright, H., Reid, H. W. Molecular genomic characterization of the viruses of malignant catarrhal fever. J CompPathol 124, 2-19 (2001).
Wang, Y., Sathish, N., Hollow, C., Yuan, Y. Functional characterization of Kaposi's sarcoma-associated herpesvirus open readingframe K8 by bacterial artificial chromosome-based mutagenesis. Journal of virology 85, 1943-1957 (2011).
Sinclair, A. J. bZIP proteins of human gammaherpesviruses. The Journal of general virology 84, 1941-1949 (2003).
Frame, F. M., Dalziel, R. G. Transcriptional control by the R-transactivator protein of alcelaphine herpesvirus-1. Vet Res Commun32, 215-223 (2008).
Dewals, B., et al. Cloning of the genome of Alcelaphine herpesvirus 1 as an infectious and pathogenic bacterial artificial chromosome. The Journal of general virology 87, 509-517 (2006).
Boudry, C., et al. The A5 gene of alcelaphine herpesvirus 1 encodes a constitutively active G-protein-coupled receptor that is nonessentialfor the induction of malignant catarrhal fever in rabbits. The Journal of general virology 88, 3224-3233 (2007).
Myster, F., et al. Viral semaphorin inhibits dendritic cell phagocytosis and migration but is not essential for gammaherpesvirusinducedlymphoproliferation in malignant catarrhal fever. Journal of virology 89, 3630-3647 (2015).
Parameswaran, N., et al. The A2 gene of alcelaphine herpesvirus-1 is a transcriptional regulator affecting cytotoxicity in virusinfectedT cells but is not required for malignant catarrhal fever induction in rabbits. Virus research 188, 68-80 (2014).
Cha, T. A., et al. Human cytomegalovirus clinical isolates carry at least 19 genes not found in laboratory strains. Journal of virology70, 78-83 (1996).
Maotani, K., et al. Amplification of a tandem direct repeat within inverted repeats of Marek's disease virus DNA during serial in vitropassage. Journal of virology 58, 657-660 (1986).
Sorel, O., et al. Small RNA deep sequencing identifies viral microRNAs during malignant catarrhal fever induced by alcelaphineherpesvirus 1. The Journal of general virology 96, 3360-3372 (2015).
Franceschi, V., et al. Bovine herpesvirus 4 immediate early 2 (Rta) gene is an essential gene and is duplicated in bovine herpesvirus 4isolate U. Vet Microbiol 148, 219-231 (2011).
Bridgen, A. The derivation of a restriction endonuclease map for Alcelaphine herpesvirus 1 DNA. Arch Virol 117, 183-192 (1991).
Russell, G. C., Stewart, J. P., Haig, D. M. Malignant catarrhal fever: a review. Vet J 179, 324-335 (2009).
Huynh, H. T., Robitaille, G., Turner, J. D. Establishment of bovine mammary epithelial cells (MAC-T): an in vitro model for bovinelactation. Experimental cell research 197, 191-199 (1991).
Gandar, F., et al. The Genome of a Tortoise Herpesvirus (Testudinid Herpesvirus 3) Has a Novel Structure and Contains a LargeRegion That Is Not Required for Replication In Vitro or Virulence In Vivo. Journal of virology 89, 11438-11456 (2015).
Wilkie, G. S., et al. First fatality associated with elephant endotheliotropic herpesvirus 5 in an Asian elephant: pathological findingsand complete viral genome sequence. Scientific reports 4, 6299 (2014).
Warming, S., Costantino, N., Court, D. L., Jenkins, N. A., Copeland, N. G. Simple and highly efficient BAC recombineering usinggalK selection. Nucleic acids research 33, e36 (2005).
Sambrook, J., Russell, D. W. Molecular Cloning. A Laboratory Manual. Vol. 1 (Cold Spring Harbor Laboratory Press, 2001).
