Herpesvirus infections in AQUATIC MAMMALS
thus kuiken1 and carlos g. das neves2
1Department of Virology, Erasmus MC and Artemis Research Institute for Wildlife Health in Europe, Rotterdam, The Netherlands
2 Norwegian School ofVeterinary Science, Department of Food Safety and Infection Biology, Section of Arctic Veterinary Medicine, Tromso, Norway
All herpesviruses identified so far in marine mammals belong to the order Herpesvirales, family Herpesviridae and subfamilies Alphaherpesvirinae or Gammaherpesvirinae.
Infection with Phocid herpesvirus 1 (PhHV1; synonyms Phocine herpesvirus 1, harbour seal herpesvirus), an alphaherpesvirus, may cause systemic disease in seals, whereas infection with Phocid herpesvirus 2 (PhHV2), a gammaherpesvirus, has not been definitively associated with disease in seals. Alphaherpesvirus infection in cetaceans may cause systemic, CNS or cutaneous disease. Gammaherpesvirus infection in cetaceans may cause genital disease (Table 1.3).Infections with PhHV1 and PhHV2 occur in harbour seals (Phoca vitulind))66'7β, and grey seals (Halichoerus grj∕pus)(77,78). PhHVl is mainly transmitted horizontally among juvenile harbour seals(83). Systemic disease from alphaherpesvirus infection has been recorded in bottlenose dolphins (Tursiops truncatusf64, a Cuvier’s beaked whale (Ziphius cavirostris)65 and a striped dolphin (Stenella coer- uleoalba)(66). CNS disease from an alphaherpesvirus infection has been recorded in a harbour porpoise (Phocoena phocoenaf67∖ Cutaneous disease from alphaherpesvirus or unspecified herpesvirus infection has been recorded in an orca (Orcinus orca)(84), a beluga whale (Delphinapterus leucas)(68), a striped dolphin(69), a harbour porpoise(70), and a bottlenose dolphin(71).
Genital disease from gammaherpesvirus infection has been recorded in a Blainville’s beaked whale (Mesoplodon densirostrisfr4 and in bottlenose dolphins*72). Transmission of genital herpesvirus in bottlenose dolphins, and probably other cetaceans, is likely to be sexual(72). Herpesvirus infection has been identified in several other marine mammal species whose range includes European waters, but associated disease has not been confirmed by light or electron microscopy (Table 1.3).The pathogenesis of PhHV1 infection in harbour seals is probably initiated by virus entry into mucosal tissues or blood. A mononuclear leucocyte- associated viraemia favours spread to lymphoid tissues, followed by dissemination to parenchymal organs. Virus replication in parenchymal organs leads to tissue necrosis and inflammation, and possibly death. Seroconversion may be associated with clinical recovery but not necessarily virus clearance1-61). Little is known about the pathogenesis of other herpesvirus infections in marine mammals.
Clinical signs reported for PhHV1 infection in harbour seals are nasal discharge and coughing, inflammation of oral mucosa, vomiting, diarrhoea, fever, anorexia, lethargy, lymphopenia and seizures1-62,85). Clinical signs are milder in older animals and are milder in grey seals than in harbour seals(77). Cetaceans with cutaneous1-86) or genital herpesvirus infection(72) appeared to be active and in good health.
Pathological changes in fatally PhHV1-infected juvenile harbour seals include necrosis in adrenal cortex, liver, brain, crypts of the small intestine, and tonsils. Intranuclear inclusion bodies (INIB) may be present at foci of acute necrosis, particularly in adrenal cortex and liver1-61,63). Fatal systemic herpesvirus infection occurred in two bottlenose dolphins(64) and in a Cuvier’s beaked whale(65) without concurrent morbillivirus infection and in a striped dolphin with concurrent morbillivirus infection(66) was associated with foci of acute necrosis in multiple organs, with INIB in both parenchymal cells and syncitial cells.
Cutaneous herpesvirus infection in cetaceans is associated with variably shaped skin lesions, which may be ulcer- ated(64,71,86). They are characterized by both necrosis and hyperplasia of epidermis, with INIB in keratinocytes. Encephalitis in a harbour porpoise was associated with INIB in many neurons(67). Genital herpesvirus infection in cetaceans is associated with plaques in mucosa of penis orTABLE 1.3 Association between herpesvirus infection and disease in marine mammal species occurring in Europe.
| Localization of disease | Host species | Pathologic diagnosis* by | Virologic diagnosis by | Subfamily | References | |||
| Histo | IHC | bgcolor=white>EMPCR | Culture | |||||
| Systemic | Harbour seal (Phoca vitulind) | yes | no | yes | yes | yes | alphab | (60-63) |
| Bottlenose dolphin (Tursiops truncatus) | yes | no | yes | yes | no | alpha | (64) | |
| Cuvier’s beaked whale (Ziphius cavirostris) | yes | no | yes | yes | no | alpha | (65) | |
| Striped dolphin (Stenella Coeruleoalbd) | yes | yes | yes | yes | no | alpha | (66) | |
| Central nervous system | Harbour porpoise (Phocoenaphocoend) | yes | yes | yes | no | no | alpha | (67) |
| Cutaneous | Beluga whale (Delphinapterus Ieucas) | yes | no | yes | no | no | not determined | (68) |
| Striped dolphin (Stenella Coeruleoalbd) | yes | no | no | no | no | not determined | (69) | |
| Harbour porpoise (Phocoenaphocoend) | yes | no | no | no | no | not determined | (70) | |
| Bottlenose dolphin (Tursiops truncatus) | yes | no | yes | yes | no | alpha | (71) | |
| Genital | Bottlenose dolphin (Tursiops truncatus) | yes | no | yes | yes | yes | gamma | (72,73) |
| Blainvilles beaked whale (Mesoplodon densirostris) | yes | no | no | yes | no | gamma | (74) | |
| Cardiac | Harp seal (Phoca groenlandicd) | yes | no | yes | no | no | not determined | (75) |
| Unconfirmed | Harbour seal (Phoca vitulind) | no | no | no | no | yes | gammac | (76) |
| Qvey seal (Halichoerus grypus) | no | no | no | yes | yes | alphab | (77) | |
| Grey seal (Halichoerus grypus) | no | no | no | yes | yes | gammac | (78) | |
| Bottlenose dolphin (Tursiops truncatus) | no | no | no | yes | no | gamma | (73) | |
| Dwarf sperm whale (Kogia sima) | no | no | no | yes | no | gamma | (73) | |
| Rlssos dolphin (Grampus griseus) | no | no | no | yes | no | gamma | (73) | |
| Bottlenose dolphin (Tursiops truncatus) | no | no | no | yes | no | alpha | (79) | |
| Striped dolphin (Stenella Coeruleoalbd) | no | no | no | yes | no | alpha and gamma | (80) | |
| Orca (Orcinus orca) | no | no | no | yes | no | alpha | (81) | |
| Sperm whale (Physeter macrocephalus) | no | no | no | yes | no | gamma | (82) | |
| False killer whale (Pseudorca crassidens) | no | no | no | yes | no | alpha | (82) | |
| Melon-headed whale (Pepenocephala electro) | no | no | no | yes | no | gamma | (82) | |
aHisto = histology; IHC = immunohistochemistry; EM = electron microscopy bPhocid herpesvirus 1
zPhocid herpesvirus 2
vulva, characterized histologically by epithelial hyperplasia and dysplasia, with INIB in epithelial cells1-72).
Diagnosis of herpesvirus infection can be done by PCR and confirmed by sequencing of the PCR product.
Samples of choice for clinical diagnosis are nasal swabs for PhHV1 infection, peripheral blood mononuclear cells for PhHV2 infection and swabs, scrapings or biopsies for cutaneous and genital herpesvirus infections. PhHV1 infection also can be diagnosed clinically by demonstration of at least a four-fold rise in virus neutralizing antibody in paired sera. Culture has been successful for PhHV1 and PhHV2 on primary seal cells and Crandell feline kidney cells)60’76’78), and for a gammaherpesvirus from bottlenose dolphins (TTHV) on primary cetacean cells and on Crandell feline kidney cells)72). Histological detection of INIB in postmortem tissue samples is suggestive of herpesvirus infection. Diagnosis becomes highly likely if suspect cells are shown to contain herpesvirus-like particles by electron microscopy or to express herpesvirus antigen by immunohistochemistry using a primary antibody against a related herpesvirus. Population screening for herpesvirus infection can be done on tissues and secretions by PCR for all herpesviruses, and on sera by ELISA or virus neutralization test for PhHV1, PhHV2 and TTHV.The management and control of outbreaks of PhHV1 infection in juvenile harbour seals at rehabilitation centres is important because such outbreaks may cause severe mortality. The severity of such outbreaks may be mitigated by appropriate quarantine measures, veterinary care and nursing of seal pups)83). In addition, a recombinant vaccine has been developed that is expected to be safe and effective inprotectingharboursealsagainstPhHV1-relateddisease)87).
Public health and domestic health concerns for marine mammal herpesviruses are low, because there is no evidence for infection of humans or domestic animals with these viruses. Given that several herpesviruses may cause severe disease and death in affected animals, these pathogens may be significant for the health of marine mammal populations.