R. D. Hunt

Acute Lymphocytic Leukemia in Owl Monkeys Inoculated with Herpesvirus saimiri

Our study demonstrates for the first time that Herpesvirus saimiri can induce acute lymphocytic leukemia in owl monkeys (Aotus trivirgatus) and that malignant lymphoma can be induced in this species of nonhuman primates by the inoculation of the virus by various routes (intravenous, sub-cutaneous, and intradermal).

In Vitro Suppression of Herpesvirus saimiri Replication by Phosphonoacetic Acid

Summary Replication of Herpesvirus sai-miri was inhibited by 60 μg/ml of phospho-noacetic acid (PAA) in owl monkey kidney cell cultures (OMK). OMK cells were not adversely affected by PAA. Concentrations over 1 mg/ml of PAA proved toxic to OMK cells. Pretreatment of virus or cells prior to infection had no inhibitory effect on HVS. The continued presence of PAA was required to suppress HVS replication. Removal of the drug from infected cell cultures even after 63 days resulted in the appearance of cytopathogenic effect. PAA had a greater degree of inhibition on HVS than Herpes hominis type 1.

Herpes virus aotus: a latent herpesvirus from owl monkeys (Aotus trivirgatus) isolation and characterization.

Summary An uninoculated batch of owl monkey kidney cell cultures yielded a viral agent 23 days after the cell culture was initiated. This agent possessed the physical, chemical, cytopathic, histological, and ultrastructural properties of a herpesvirus. Random testing of owl monkey sera showed the presence of high titered neutralizing antibodies against this new agent. Herpesvirus simplex, Herpesvirus T., Herpesvirus B, Herpesvirus suis, Herpesvirus saimiri, infectious bovine rhinotraecheitis, and Herpesvirus saguinus, OMKI 372, and OMKI 68-69 antisera failed to neutralize the infectivity of this new agent. In cell cultures the virus grew best in cells of owl monkey origin. It also grew (poorly) in cebus monkey kidney cell cultures, some batches of squirrel monkey kidney cells, in Vero, BSC-1, human embryonic lung, whole human embryo and human embryo skin and muscle cells. It failed to form plaques under an agar overlay and does not form pocks on chorioallantoic membranes of embryonated eggs. Based on these findings, the name Herpesvirus aotus has been suggested. Owl monkey kidney cell cultures and owl monkey sera, when used for any work with other members of the herpesvirus group, ought to be employed with caution. The case reported here represents the first herpesvirus isolated from an owl monkey. Even though the pathogenic spectrum of this virus has not been established, being a herpesvirus, it should be regarded as potentially dangerous. Investigators who use owl monkeys should be aware of this new herpesvirus.

Herpesvirus B Infection

Ordinary Herpesvirus B infection in rhesus monkeys (Macaca mulatta) and other macaques is typically an inapparent latent infection (Burnett et al. 1939; Palmer 1987; Hartley 1964, 1966). Gross lesions are generally associated with primary infection, but the lesions are only rarely recorded. This suggests that they are small and do not lead to overt signs or are overlooked due to infrequent and inadequate examination. When present, gross lesions resemble those seen in H. simplex infection in humans, (p. 82, this volume), consisting of vesicles which rapidly progress to ulcers (Keeble et al. 1958; Keeble 1960). Lesions are most frequent on the dorsal surface of the tongue and at the mucocutaneous junction of the lips (Fig. 76). Other parts of the oral mucous membranes may also be affected and occasionally the infection occurs as conjunctivitis. Healing without scars is usually complete within 1–2 weeks. Less often, B virus infection causes widespread stomatitis with extension into the pharynx and esophagus. This infection rarely becomes disseminated, which is often fatal. The clinical and gross findings are typically similar in other species of macaques, which include M. fascicularis, M. fuscata, M. arctoides, M. cyclopis, and M. radiata. Disseminated disease and fatalities have been reported most frequently in M. radiata and M. fascicularis (Deniel et al. 1975; Espana 1973; Hartley 1964;).

Arrested Spermatogenesis:Aotus trivirgatus, Saimiri sciureus, and Macaca mulatta

Owl monkeys (Aotus trivirgatus) testicles are smaller than those of other nonhuman primates of comparable body size. The testicles are soft and brown on cut surface. Male squirrel monkeys (Saimiri sciureus), during the mating season, which in the northern hemisphere is the winter months, develop a characteristic muscular or fatty development, particularly about the upper torso, shoulders and arms, a condition referred to as “fatting”. Associated with this is an increase in testicular size and total body weight. These characteristics are gradually lost beginning in April, completely disappear by May, and do not return until late December (Du Mond and Hutchinson 1967). A similar seasonal increase in testicular size and body weight has been described in lemurs (Hafez 1971).

Gastroenteritis Due to Paramyxovirus

Gross examination reveals congestion with petechiae and ecchymoses in the mucosa of the stomach, cecum, colon and occasionally the small intestine. Peyer’s patches may be congested and prominent and mesenteric lymph nodes and the spleen may be enlarged.

Glomerulonephritis, Owl Monkeys

Gross changes often are not evident, the kidneys appearing entirely normal. With progression of the disease, the kidneys become mottled mahogany and tan in color and eventually uniformly tan or tan with yellowish or gray-white foci up to 1 mm in diameter scattered throughout the cortex. In severe cases the pale foci are larger and confluent. Linear pale areas, extending from the capsule to the medulla and resembling infarcts, are often present. The capsular surface may be irregular, and the kidneys are enlarged. The medulla and pelvis are usually normal.

Herpesvirus saimiri and Herpesvirus ateles Infection

Experimental injection of Herpesvirus saimiri into owl monkeys (Aotus trivirgatus), several species of tamarins and marmosets (Saguinus oedipus, S. fuscicollis, S. nigricollis, S. mystax, and Callithrix jaccuhus), howler monkeys (Alouatta caraya), and spider monkeys (Ateles geoffroyi) results in lymphoma or lymphocytic leukemia (Cicmanec et al. 1974; Deinhardt 1975; Dienhardt et al. 1974; Fleckenstein and Desrosiers 1982; Hunt et al. 1972a,b, 1976; Hunt 1978; Rangan et al. 1977; Melendez et al. 1971b, 1972; Wright et al. 1977; Wolfe et al. 1971). Lymphoproliferative disease has been described in cebus monkeys (C. albifrons) but it has not been reproduced (Melendez et al. 1970).

Herpesvirus platyrrhinae Infection

The pathological and biological features of Herpesvirus T infection are remarkably similar to Herpesvirus simplex infection as described on p. 82, this volume. The virus, however, is distinct and only New World monkeys are naturally affected (Holmes et al. 1964; Melnick et al. 1964). Herpesvirus T is carried by squirrel monkeys (Saimiri sciureus) (Melendez et al. 1966) in which serum antibodies are very frequent but clinical disease only rarely recorded. Documented lesions in squirrel monkeys consist of vesicles and ulcers of the oral mucous membranes and lips and have a very similar gross and microscopic appearance to H. simplex lesions in human beings (Figs. 100-105) (Daniel et al. 1967; King et al. 1967). Circulating serum neutralizing antibodies to Herpesvirus T have been detected also in cinnamon ringtail monkeys (Cebus albifrons) and spider monkeys (Ateles spp.), which might also be natural reservoir hosts but no clinical disease has been described in these two species (Holmes et al. 1966).