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Toxicologic Pathology
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Histologic Lesions in Cynomolgus Monkeys (Macaca fascicularis) Naturally Infected with Simian Retrovirus Type D: Comparison of Seropositive, Virus-Positive, and Uninfected Animals

Roberto E. Guzman

Drug Safety Evaluation, Pfizer Central Research, Groton, Connecticut 06340, reguzman{at}students.uiuc.edu.

Roy L. Kerlin

Drug Safety Evaluation, Pfizer Central Research, Groton, Connecticut 06340

Thomas E. Zimmerman

Drug Safety Evaluation, Pfizer Central Research, Groton, Connecticut 06340

Simian retrovirus (SRV) type D is a common cause of simian acquired immunodeficiency syndrome (SAIDS), a usually fatal immunosuppressive disease of macaques. Associated gross and histologic lesions have been well described for the rhesus macaque (Macaca mulatta) in experimental and natural infections. However, morphologic changes induced by this virus at the gross and light-microscopic level have not been documented in the cynomolgus macaque (Macaca fascicularis). In 1996, sporadic cases of anemia, weight loss, and diarrhea were noted in a colony of cynomolgus macaques in our research facility. Out of 28 animals, 24 tested positive for SRV by serology or virus isolation. Animals could mainly be classified into 1 of 2 categories: 1) positive for virus isolation but negative for SRV antibody and 2) negative for virus isolation but antibody positive. During the process of eliminating the virus from the colony, a complete postmortem examination was performed on the 24 infected animals that had to be culled. Twelve SRVnegative animals were available as controls. Minimal to mild follicular lymphoid infiltrates were seen in various organ systems in 75% of the negative animals, compared with moderate to marked infiltrates in 83% of infected animals. Lymphoid infiltrates were more common in the brain, bone marrow, and salivary gland of viremic animals and were rare to nonexistent in seropositive or negative animals. Lymphoid hyperplasia was present in 38% of the infected animals, whereas lymphoid depletion was seen in 47% of the infected animals. Overall, lesions were of greater severity in viremic animals than in virus-negative or seropositive animals. Overall, infected animals had lower, statistically significant hematocrit and lymphocyte values. Viremic animals had significantly lower hematocrit, white blood cell, lymphocyte, and neutrophil values than did controls. Only 1 out of 24 infected animals had clinical signs that were consistent with the definition of SAIDS, and none had evidence of opportunistic infections. Lesions were similar to those already reported in other species of macaques, but the absence of severe illness that was consistent with SAIDS in most viremic animals suggests that there may be a different manifestation of disease in the cynomolgus.

Key Words: Cynomolgus macaque • simian retrovirus (SRV) • immunodeficiency syndromes • lymphoid hyperplasia • lymphoid depletion • lymphoid infiltrates

Toxicologic Pathology, Vol. 27, No. 6, 672-677 (1999)
DOI: 10.1177/019262339902700609


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