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Journal of Virology, December 2009, p. 12129-12138, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01523-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Origin and Phylodynamics of Rabbit Hemorrhagic Disease Virus {triangledown} ,{dagger}

Peter J. Kerr,1 Andrew Kitchen,2 and Edward C. Holmes2,3*

CSIRO Entomology, GPO Box 1700, Canberra, ACT 2601, Australia,1 Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802,2 Fogarty International Center, National Institutes of Health, Bethesda, Maryland 208923

Received 22 July 2009/ Accepted 9 September 2009

To determine the origin, phylogenetic relationships, and evolutionary dynamics of rabbit hemorrhagic disease virus (RHDV), we examined 210 partial and complete capsid gene nucleotide sequences. Using a Bayesian Markov chain Monte Carlo approach, we estimated that these sequences evolved at a rate of 3.9 x 10–4 to 11.9 x 10–4 nucleotide substitutions per site per year. This rate was consistent across subsets of data, was robust in response to recombination, and casts doubt on the provenance of viral strains isolated from the 1950s to the 1970s, which share strong sequence similarity to modern isolates. Using the same analysis, we inferred that the time to the most recent common ancestor for a joint group of RHDV and rabbit calicivirus sequences was <550 years ago and was <150 years ago for the RHDV isolates that have spread around the world since 1984. Importantly, multiple lineages of RHDV were clearly circulating before the major Chinese outbreak of 1984, a finding indicative of an early evolution of RHDV virulence. Four phylogenetic groups within RHDV were defined and analyzed separately. Each group shared a common ancestor in the mid-1960s or earlier, and each showed an expansion of populations starting before 1984. Notably, the group characterized by the antigenic variant RHDVa harbors the greatest genetic diversity, compatible with an elevated fitness. Overall, we contend that the high virulence of RHDV likely evolved once in the early part of the 20th century, well before the documented emergence of rabbit hemorrhagic disease in 1984.

* Corresponding author. Mailing address: Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, PA 16802. Phone: (814) 863-4689. Fax: (814) 865-9131. E-mail: ech15{at}psu.edu

{triangledown} Published ahead of print on 16 September 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, December 2009, p. 12129-12138, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01523-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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