Ronald D. Hunt

An immunohistologic study of granulomatous inflammation in SIV-infected rhesus monkeys.

We studied granulomatous inflammation in simian AIDS using histologic, immunohistologic, and in situ hybridization techniques. Complete Freunds adjuvant was used to induce granulomas in two control animals and two macaques infected with simian immunodeficiency virus (SIV) and having low peripheral CD4+ T cell counts. Control animals developed large (>2 cm diameter) epithelioid granulomas containing CD68+ macrophages (mφs), epithelioid mφs and multinucleated giant cells (MNGCs), CD4+ and CD8+ T cells, and small perivascular collections of CD20+ B cells. Lymphocytes rarely expressed proliferating cell nuclear antigen (Ki‐67), and only rare endothelial cells expressed vascular cell adhesion molecule 1 (VCAM‐1). In contrast, SIV+ animals had smaller (<0.5 cm diameter) epithelioid granulomas characterized by numerous large, dense CD8+, CD20+ lymphocyte aggregates with prominent local division (Ki‐67+). Despite low blood CD4+ T cell numbers, there was a substantial CD4+ T cell infiltrate, accompanied by enhanced endothelial VCAM‐1 expression. These granulomas contained no detectable SIV antigen or RNA. Thus, in simian AIDS, experimentally induced granulomatous responses are grossly attenuated, yet associated with increased local endothelial‐leukocyte signaling and lymphocyte division.

Spontaneous Herpes-T Infection in the Owl Monkey (Aotus trivirgatus):

The pathological features of spontaneous herpes-T infection in 6 owl monkeys (Aotus trivirgatus) were characterized by the presence of intranuclear inclusion bodies in epithelial and mesenchymal cells associated with necrosis of the skin, oral mucous membranes, esophagus, small intestine, cecum, colon, nasal mucous membranes, larynx, trachea, lung, liver, spleen, lymph nodes, adrenal gland, and bone marrow. The inclusion bodies and the lesions are similar to herpes virus infections of other animal species. A virus was isolated from 5 monkeys, which on the basis of serum neutralization tests in vitro was identified as herpes-T.

Isolation of Herpes-T virus from a spontaneous disease in squirrel monkeys (Saimiri sciureus)

Herpes-T virus was isolated from 2 of 4 clinically ill squirrel monkeys. The clinical manifestations of the disease in the monkeys was characterized by oral and labial lesions. From one of two animals sacrificed for histopathological examination, Herpes-T virus was isolated from the tongue and salivary gland. Herpes-T was isolated from the oral swab of one of the two live monkeys on the day of arrival in our laboratory and again on the 4th day. The anal swabs collected from both these monkeys failed to yield virus. The sera of these monkeys collected on the day of arrival showed a neutralization index (NI) of 1.0 and 1.5 against Herpes-T virus. The convalescent sera, collected two weeks later, showed a NI of 3.5 and 4.0 respectively for the same virus. Clear plaques ranging in size from 2 to 3 mm were produced in chick fibroblast and rabbit kidney primary monolayers. This is the first report of the isolation of Herpes-T virus from naturally infected squirrel monkeys. This data further supports that the squirrel monkey is a natural host of Herpes-T virus.

Congenital Encephalitozoonosis in a Squirrel Monkey (Saimiri sciureus)

Multifocal granulomatous encephalitis associated with invasion of the brain by Encephalitozoon cuniculi was present in a squirrel monkey less than 24 h old. This appeared to be a congenital infection. The infants dam was clinically normal.

Tumour induction with DNA of oncogenic primate herpesviruses

THE viruses Herpesvirus saimiri and H. ateles are highly oncogenic agents of New World primates. The viruses are not pathogenic in the natural host species (squirrel and spider monkeys, respectively), but induce malignant neoplastic diseases of the lymphatic system in various other primates1,2 and in rabbits3. Marmoset monkeys (Saguinus sp.) are the most susceptible animals to tumour induction, as infection with these viruses invariably results in rapidly progressing malignant lymphoma or acute lymphocytic leukaemia within a few weeks4,5. H. saimiri and H. ateles are related viruses; they share common antigens6 and some homologous DNA sequences7. DNA from both viruses is infectious in permissive owl monkey kidney (OMK) cell cultures8. We report here that the isolated DNA from these two herpesviruses can also cause malignant tumours in animals.

Simian Neonatology III. The Causes of Neonatal Mortality

The causes of death were studied in 82 perinatal and neonatal monkeys. Forty-three of the 82 neonatal deaths were caused by inflammatory diseases (mainly pneumonia), intrauterine distress, and trauma. In 28 of the 82 monkeys, a major disease process could not be demonstrated. Intrauterine distress and antepartum death with maceration were commoner causes of death in premature infants; trauma and inflammatory disease occurred more often in mature infants. Forty-nine of the 82 neonatal deaths occurred before the second day of life. During the last 3 weeks of the neonatal period, the majority of deaths were caused by infection.

Immunophenotypic characterization of mononuclear phagocytes and dendritic cells in lymphoid organs of the rhesus monkey

Mononuclear phagocytes and dendritic cells are potent antigen-presenting cells that localize to distinct microenvironmental compartments in many different organs. These cells are particularly plentiful in spleen and lymph node. Recently, these cells have been identified and immunophenotypically characterized in human tissue sections using monoclonal antibodies. However, similar studies in animal species, particularly those representing models of human diseases, have yet to be completely performed. We have evaluated 18 monoclonal reagents raised against human determinants for their reactivity with macrophages and dendritic cells in lymphoid organs of rhesus monkeys. Six of the 18 (EBM11, 25F9, Mol, R4/23, To5, and SK9) produced labeling patterns in rhesus monkey lymphoid tissue that paralleled the staining patterns described for human tissues. Seven others (KB90, FMC17, Mo3, PHM3, PHM2, G16/1, and 27E10) stained varying subsets of specific cells types in these simian tissues. These reagents are requisite for the future study in an experimental animal of the afferent immune response in both normal and disease states.

Simian Neonatology: II. Neonatal Pathology

Spontaneous gross and microscopic lesions were studied in 82 perinatal and neonatal monkeys of various species. Ninety-seven lesions were found in the body systems examined. The system at greatest risk was the respiratory system (33 lesions), at the least risk, the cardiovascular system (four lesions). Lesions were inflammatory, degenerative, vascular, and of other types, such as intrauterine aspiration and congenital anomalies. Differences in the type and distribution of lesions in the various systems were found between premature and mature infants.

OVERVIEW OF AIRBORNE CONTAGION IN ANIMALS

Airborne spread of viral infections is a predominant mode for transmission of various diseases in man. Although a number of viral infections can be transmitted by airborne route, the common cold and influenza are probably the two viral diseases transmitted most frequently by the airborne route. Airborne transmission of viral diseases is of particular importance in veterinary medicine because of the economic impact outbreaks of severe infections can have on the food production industry. This overview seeks to highlight factors favoring and promoting survival of viruses in air and to summarize three viral diseases to illustrate the magnitude of losses resulting from major viral disease epidemics in the poultry and livestock industry.

Failure of Herpesvirus saimiri to enhance atherogenesis in owl monkeys (Aotus trivirgatus)

A retrospective study was performed to evaluate the potential of a mammalian oncogenic virus, Herpesvirus saimiri, to cause atherosclerosis in owl monkeys (Aotus trivirgatus). This was undertaken since an avian oncogenic herpesvirus, Mareks disease virus, does so in chickens. Data from earlier studies were reviewed and 3 groups of animals were selected. These included 23 animals infected with herpesvirus that died an average of 156 days later with malignant lymphoma; 11 infected an average of 207 days before being killed without lymphoma; and 21 uninfected control animals that died from a variety of diseases. Aortas and hearts from all animals were recovered from storage in formalin and examined for histopathological evidence of atherosclerosis in aortas and coronary arteries. Mild to moderate atherosclerosis characterized by intimal proliferation and the presence of fat droplets was present in 60% of the monkeys and did not differ in occurrence between the groups. Mean intimal thickness did not vary significantly between groups either. A case of naturally-occurring severe atherosclerosis is also reported here. Thus, although this species is susceptible to atherosclerosis, neither the occurrence nor severity of that disease is affected by infection with an oncogenic virus within the time periods studied here.