Oyster reefWhere did herpesviruses come from?

Humans, of course, have 8 different herpesviruses that are remarkably good at infecting us. Humans aren’t exceptional: We know of 200-odd herpesviruses so far, and more are being identified practically daily. It’s likely that virtually every animal species has its own set of unique herpesviruses. This is probably because herpesviruses are very host-restricted (rarely infecting more than a single species) and set up latent, life-long infection. When an animal population speciates, its complement of herpesviruses speciates along with it.

How long has this been happening? What mammal, dinosaur, fish, or trilobite did the first herpesvirus infect?

Herpes simplex structure
Herpes simplex virus structure1

It was certainly before the mammal/reptile split, some 300 million years ago. Mammalian, reptilian, and avian herpesviruses cluster very nicely together by DNA and amino acid sequence, with some 40 genes that are clearly homologous. (Mammalian herpesvirus are grouped into alpha, beta, and gammaherpesvirus based originally on biology and, subsequently, on genome sequence; but bird and reptile herpesviruses so far have all been alphaherpesviruses, so this tripartite split did happen after the synapsid reptiles diverged from the other lineages that led to birds and turtles and so on.)2

How to spot a herpesvirus
Genome:
• Linear, double-stranded DNA
• 120 – 250,000 base pairs
• Unique short and long regions
• Inverted repeats flank UL and US
Structure:
• Core containing DNA
• Icosahedral (T=16) capsid
• Amorphous tegument between capsid and envelope
Amphibians and fish herpesviruses are quite different from mammal and reptile groups, and cluster into their own broad family, sharing a number of closely-related genes. Genome similarity is low or non-existent, but the pathognomic physical structure, capsid architecture, and overall DNA organization is entirely consistent. These are clearly herpesviruses that diverged over 400 million years ago, and have evolved away all but the faintest semblance of sequence similarity.

Impressive as it is to be able to reconstruct virus evolution for nearly a half billion years, we’re not done yet. In 1972, a herpesvirus of oysters was identified!3 So far this is the only herpesvirus of invertebrates to be definitively identified (there may be others, such as a herpesvirus of abalones,4 but as far as I know only the Ostreid herpesvirus has had its genome sequenced,5 so it’s quite possible that the abalone virus is the same thing). As with the amphibian and fish herpesviruses, OsHV has the very characteristic herpesvirus structure and organization, but at the sequence level it’s very different from either of the other major branches, making this the only known representative of a third major group of herpesviruses.

…the ancient herpesvirus from which modern herpesviruses are presumed to have descended was in existence around a billion years ago and was recognisably a herpesvirus. This pushes the origins of herpesviruses so far back in time that it is difficult to see how we might discern the nature of even earlier ancestors. 6

ResearchBlogging.orgCan we push ancestry back beyond a billion years? Not easily; DNA sequence and even characteristic capsids and so on can only take us so far. But protein three-dimensional structure is more conserved than is sequence, and a couple of groups have shown common elements in folds of herpesvirus and bacteriophage proteins that suggest a common ancestry past the eukaryote/prokaryote divergence:7

This linkage between the most abundant set of bacteriophages and a major family of eukaryotic viruses highlights the growing evidence of relationships across these major biological divides. In light of this and other recent studies, it is becoming increasingly plausible that extant viruses may have arisen from a relatively small number of primordial progenitors. 8


  1. Three-Dimensional Structure of Herpes Simplex Virus from Cryo-Electron Tomography
    Grünewald et al., Science 302:1396 – 1398 (2003) []
  2. It’s also been suggested that some of the avian and mammalian viruses are too closely related to have diverged that long ago, and may indicate ancient interspecies transmissions some 100 million years ago. See: Toward a Comprehensive Phylogeny for Mammalian and Avian Herpesviruses Duncan J. McGeoch, Aidan Dolan, and Adam C. Ralph Journal of Virology 74:10401-10406 (2000) []
  3. Farley, C.A., Banfield, W.G., Kasnic, G., Foster, W.A. (1972). Oyster herpes-type virus. Science, 178(62), 759-760.[]
  4. Herpes-like virus infection causing mortality of cultured abalone Haliotis diversicolor supertexta in Taiwan. Chang PH, Kuo ST, Lai SH, Yang HS, Ting YY, Hsu CL, Chen HC. Dis Aquat Organ. 2005 Jun 14;65(1):23-7 []
  5. A novel class of herpesvirus with bivalve hosts. Andrew J. Davison, Benes L. Trus, Naiqian Cheng, Alasdair C. Steven, Moira S. Watson, Charles Cunningham, Rose-Marie Le Deuff, and Tristan Renault. J Gen Virol 86 (2005), 41-53 .
    The accession number of the OsHV-1 DNA sequence is AY509253.[]
  6. Davison, A. (2002). Comments on the phylogenetics and evolution of herpesviruses and other large DNA viruses. Virus Res 82, 127-132.[]
  7. Common Ancestry of Herpesviruses and Tailed DNA Bacteriophages. Matthew L. Baker, Wen Jiang, Frazer J. Rixon, and Wah Chiu. Journal of Virology, December 2005, p. 14967-14970, Vol. 79, No. 23.
    Also see Structure of an archaeal virus capsid protein reveals a common ancestry to eukaryotic and bacterial viruses.  Reza Khayat, Liang Tang, Eric T. Larson, C. Martin Lawrence, Mark Young, and John E. Johnson. Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18944-9
    and
    Structural and functional similarities between the capsid proteins of bacteriophages T4 and HK97 point to a common ancestry.  Fokine A, Leiman PG, Shneider MM, Ahvazi B, Boeshans KM, Steven AC, Black LW, Mesyanzhinov VV, Rossmann MG. Proc Natl Acad Sci U S A. 2005 May 17;102(20):7163-8. []
  8. Common Ancestry of Herpesviruses and Tailed DNA Bacteriophages. Matthew L. Baker, Wen Jiang, Frazer J. Rixon, and Wah Chiu. Journal of Virology, December 2005, p. 14967-14970, Vol. 79, No. 23.[]