Pathological and molecular aspects of fatal endotheliotropic herpesviruses of elephants

Since 1980, there have been at least 34 confirmed deaths or serious hemorrhagic illnesses in captive Asian and African elephants located in North America, Europe and the Middle East associated with newly recognized endotheliotropic herpesviruses. They are known as the elephant endotheliotropic herpesviruses of which one is fatal for Asian elephants (Elephas maximus) and the other for African elephants (Loxodonta africana). The disease syndrome affects predominantly young elephants and has been described in North America, Europe, and Israel. Recent findings suggest that localized herpesvirus-associated lesions in healthy African elephants, including skin papillomas, vulval lymphoid patches, and pulmonary nodules may be sources of the herpesvirus that causes disseminated disease in both species. Affected animals have ultrastructural evidence of herpesvirus-like particles in endothelial cells of the heart, liver and tongue. Consensus primer PCR combined with sequencing yielded molecular evidence that confirmed the presence of two novel but related herpesviruses associated with the disease, one in Asian elephants and the second in African elephants. Sequence analysis of lambda libraries constructed from diseased tissue obtained from deceased Asian and African elephants indicates that for most of the conserved herpesvirus genes, the protein sequences have higher identity to the betaherpesviruses than to the alpha or gammaherpesvirus subgroups, with some notable exceptions. Two prominent differences are the presence of a thymidine kinase gene in both viruses, and the presence of the small subunit of ribonucleotide reductase in at least one of the viruses. Neither of these two genes have been described within the betaherpesvirus group. The elephant endotheliotropic herpesviruses may therefore constitute the first examples of a new subgroup of herpesviruses.