Evolution of Bovine herpesvirus 4: recombination and transmission between African buffalo and cattle

Bovine herpesvirus 4 (BoHV 4) has been isolated from cattle throughout the world, but virological and serological studies have suggested that the African buffalo is also a natural host for this virus. We have previously found that the Bo17 gene of BoHV-4 was acquired from an ancestor of the African buffalo, probably around 1.5 Myr ago. Analysis of the variation of the Bo17 gene sequence among BoHV-4 strains suggested a relatively ancient transmission of BoHV 4 from the buffalo to the Bos primigenius lineage, followed by a host dependent split between zebu and taurine BoHV 4 strains. In the present study, the evolutionary history of BoHV-4 was investigated by analysis of five gene sequences from each of nine strains representative of the viral species: three isolated from African buffalo in Kenya, and six from cattle from Europe, N. America and India. No two gene sequences had the same evolutionary tree, indicating that recombination has occurred between divergent lineages: six recombination events were delineated for these sequences. Nevertheless, exchange has been infrequent enough that a clonal evolutionary history of the strains could be discerned, upon which the recombination events were superimposed. The dates of divergence among BoHV-4 lineages were estimated from synonymous nucleotide substitution rates. The inferred evolutionary history suggests that African buffalo were the original natural reservoir of BoHV-4, and that there have been at least three independent transmissions from buffalo to cattle, probably via intermediate hosts, and – at least in the case of N. American strains – within the last 500 years.