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2014 ; 88
(23
): 13547-69
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Comparative genome analysis of four elephant endotheliotropic herpesviruses,
EEHV3, EEHV4, EEHV5, and EEHV6, from cases of hemorrhagic disease or viremia
#MMPMID25231309
Zong JC
; Latimer EM
; Long SY
; Richman LK
; Heaggans SY
; Hayward GS
J Virol
2014[Dec]; 88
(23
): 13547-69
PMID25231309
show ga
The genomes of three types of novel endotheliotropic herpesviruses (elephant
endotheliotropic herpesvirus 1A [EEHV1A], EEHV1B, and EEHV2) associated with
lethal hemorrhagic disease in Asian elephants have been previously well
characterized and assigned to a new Proboscivirus genus. Here we have generated
112 kb of DNA sequence data from segments of four more types of EEHV by direct
targeted PCR from blood samples or necropsy tissue samples from six viremic
elephants. Comparative phylogenetic analysis of nearly 30 protein-encoding genes
of EEHV5 and EEHV6 show that they diverge uniformly by nearly 20% from their
closest relatives, EEHV2 and EEHV1A, respectively, and are likely to have similar
overall gene content and genome organization. In contrast, seven EEHV3 and EEHV4
genes analyzed differ from those of all other EEHVs by 37% and have a G+C content
of 63% compared to just 42% for the others. Three strains of EEHV5 analyzed
clustered into two partially chimeric subgroups EEHV5A and EEHV5B that diverge by
19% within three small noncontiguous segments totaling 6.2 kb. We conclude that
all six EEHV types should be designated as independent species within a proposed
new fourth Deltaherpesvirinae subfamily of mammalian herpesviruses. These virus
types likely initially diverged close to 100 million years ago when the ancestors
of modern elephants split from all other placental mammals and then evolved into
two major branches with high- or low-G+C content about 35 million years ago.
Later additional branching events subsequently generated three paired sister
taxon lineages of which EEHV1 plus EEHV6, EEHV5 plus EEHV2, and EEHV4 plus EEHV3
may represent Asian and African elephant versions, respectively. IMPORTANCE: One
of the factors threatening the long-term survival of endangered Asian elephants
in both wild range countries and in captive breeding populations in zoos is a
highly lethal hemorrhagic herpesvirus disease that has killed at least 70 young
Asian elephants worldwide. The genomes of the first three types of EEHVs (or
probosciviruses) identified have been partially characterized in the preceding
accompanying paper (L. K. Richman, J.-C. Zong, E. M. Latimer, J. Lock, R. C.
Fleischer, S. Y. Heaggans, and G. S. Hayward, J. Virol. 88:13523-13546, 2014,
http://dx.doi.org/10.1128/JVI.01673-14). Here we have used PCR DNA sequence
analysis from multiple segments of DNA amplified directly from blood or necropsy
tissue samples of six more selected cases of hemorrhagic disease to partially
characterize four other types of EEHVs from either Asian or African elephants. We
propose that all six types and two chimeric subtypes of EEHV belong to multiple
lineages of both AT-rich and GC-rich branches within a new subfamily to be named
the Deltaherpesvirinae, which evolved separately from all other mammalian
herpesviruses about100 million years ago.