Experimental adenovirus hemorrhagic disease in white-tailed deer fawns.

Infection with a newly described endotheliotropic adenovirus was the cause of a 1993 epizootic reminiscent of hemorrhagic disease in California mule deer (Odocoileus hemionus columbianus and O. hemionus hemionus). Pulmonary edema and intestinal luminal hemorrhage, or necrotizing stomatitis associated with systemic or localized vasculitis, respectively, were common lesions seen in animals that died during the epizootic. In order to determine if white-tailed deer (Odocoileus virginianus) also are susceptible to infection and fatal disease with the deer adenovirus, eight white-tailed deer fawns (4- to 6-mo-old) were inoculated with purified deer adenovirus. Four were inoculated intravenously and four were inoculated through the mucous membranes. Seven days post-inoculation, one of the fawns inoculated intravenously died. Pulmonary edema and hemorrhagic enteropathy were associated with pulmonary and intestinal vasculitis with systemic multiorgan distribution of endotheliotropic adenovirus as demonstrated by transmission electron microscopy and immunohistochemistry. Adenovirus was reisolated from lung homogenates of the fawn that died of adenovirus hemorrhagic disease.

Lesions and transmission of experimental adenovirus hemorrhagic disease in black-tailed deer fawns.

Adenovirus infection was the cause of an epizootic of hemorrhagic disease that is believed to have killed thousands of mule deer (Odocoileus hemionus) in California during the latter half of 1993. A systemic vasculitis with pulmonary edema and hemorrhagic enteropathy or a localized vasculitis associated with necrotizing stomatitis/pharyngitis/glossitis or osteomyelitis of the jaw were common necropsy findings in animals that died during this epizootic. To study transmission of adenovirus infection in deer and susceptibility of black-tailed deer (Odocoileus hemionus columbianus) fawns to adenovirus infection, six 3-6-month-old black-tailed fawns were divided into two treatment groups. One group was inoculated intravenously and the other group was inoculated through the mucous membranes of the eyes, nose and mouth with purified adenovirus. Each treatment group also included two additional fawns (four total) that were not inoculated but were exposed to inoculated animals (contact animals). One fawn served as a negative control. Between 4 and 16 days postinoculation, 8/10 fawns developed systemic or localized infection with lesions identical to lesions seen in animals with natural disease that died during the epizootic. Transmission was by direct contact, and the route of inoculation did not affect the incubation period or the distribution of the virus (systemic or the localized infection). Immunohistochemical analysis using polyclonal antiserum against bovine adenovirus type 5 demonstrated staining in endothelial cells of vessels in numerous tissues in animals with systemic infection and endothelial staining only in vessels subtending necrotic foci in the upper alimentary tract in animals with the localized form of the disease. All inoculated or exposed animals had staining in the tonsillar epithelium. Transmission electron microscopic examination of lung and ileum from two fawns with pulmonary edema and hemorrhagic enteropathy demonstrated endothelial necrosis and adenovirus virions in endothelial cell nuclei. Adenovirus was reisolated in black-tailed deer pulmonary artery endothelial cells using lung homogenate of the first fawn that developed systemic adenovirus infection. Serum virus neutralization test results suggest that this deer adenovirus is a new serotype.

Experimental adenovirus hemorrhagic disease in yearling black-tailed deer.

An apparently novel adenovirus was associated with an epizootic of hemorrhagic disease that is believed to have killed thousands of mule deer (Odocoileus hemionus) in California (USA) during 1993-1994. A systemic vasculitis with pulmonary edema and hemorrhagic enteropathy or a localized vasculitis associated with necrotizing stomatitis/pharyngitis/glossitis or osteomyelitis of the jaw were common necropsy findings in animals that died during this epizootic. Six black-tailed yearling deer (O. hemionus columbianus) were inoculated with purified adenovirus isolated from a black-tailed fawn that died of acute adenovirus hemorrhagic disease during the epizootic. Three of six inoculated deer also received intramuscular injections of dexamethasone sodium phosphate every 3 days during the study. Eight days post-inoculation, one deer (without dexamethasone) developed bloody diarrhea and died. Necropsy and histopathologic findings were identical to lesions in free-ranging animals that died of the natural disease. Hemorrhagic enteropathy and pulmonary edema were the significant necropsy findings and there was microscopic vascular damage and endothelial intranuclear inclusion bodies in the vessels of the intestines and lungs. Adenovirus was identified in necrotic endothelial cells in the lungs by fluorescent antibody staining, immunohistochemistry and by transmission electron microscopy. Adenovirus was reisolated from tissues of the animal that died of experimental adenovirus hemorrhagic disease. Similar gross and microscopic lesions were absent in four of six adenovirus-inoculated deer and in the negative control animal which were necropsied at variable intervals during the 14 wk study. One deer was inoculated with purified adenovirus a second time, 12 wk after the first inoculation. Fifteen days after the second inoculation, this deer developed severe ulceration of the tongue, pharynx and rumen and necrotizing osteomyelitis of the mandible which was associated with vasculitis and thrombosis of adjacent large vessels and endothelial intranuclear inclusions. Transmission electron microscopy demonstrated adenovirus within the nuclei of vascular cells and immunohistochemistry demonstrated adenovirus antigen within tonsilar epithelium and in rare vessels.

Systemic adenovirus infection associated with high mortality in mule deer (Odocoileus hemionus) in California.

Seventeen counties in northern California experienced epizootics of high mortality in the mule deer (Odocoileus hemionus) population during the latter half of 1993. Thirteen deer submitted to the California Veterinary Diagnostic Laboratory System as part of this natural die-off had systemic adenovirus infection. Pulmonary edema was present in all 13 deer. Erosions, ulceration, and abscessation of the upper alimentary tract occurred in 7/13 deer. Four of 13 deer had hemorrhagic enteritis. All 13 deer had widespread systemic vasculitis with endothelial intranuclear inclusions. Fluorescein isothiocyanate-labeled antibody directed against bovine adenovirus type 5 bound to antigen in endothelial cells. Adenovirus was identified by transmission electron microscopy within the nuclei of endothelial cells in 6/6 deer examined. An adenovirus was isolated from lung homogenates of one deer that were cultured on black-tailed deer pulmonary artery endothelial cells. With the exception of the intranuclear inclusions evident on histologic evaluation, gross and histologic changes were similar to those described for bluetongue virus infection and epizootic hemorrhagic disease virus infection in white-tailed deer. Nine additional deer were emaciated and had pharyngeal abscesses with focal vasculitis, which may represent the chronic affects of previous nonfatal adenovirus infection.