Search

Simian T-cell lymphotropic viruses (STLV), the nonhuman primate counterparts of human T-cell lymphotropic viruses (HTLV), are endemic in many populations of African and Asian monkeys and apes. Although an etiologic link between STLV1 infection and lymphoproliferative disorders such as malignant lymphomas has been suggested in some nonhuman primate species, most STLV infections are inapparent, and infected animals remain clinically healthy. The retroviral transactivator, tax, is well known to increase transcription of viral and cellular genes, resulting in altered cytokine profiles. This study compared the cytokine profiles of peripheral blood mononuclear cell (PBMC) cultures from 25 STLV1-seropositive rhesus macaques (Macaca mulatta) with those of age- and sex-matched seronegative controls. IFNγ, TNFα, IL10, and IL2 levels in unstimulated PBMC culture supernatants were measured at 24, 48, and 72 h by using enzyme immunoassays. IFNγ concentrations were found significantly higher in the supernatants of PBMC cultures of seropositive monkeys as compared with seronegative controls. In addition, although IL2 concentrations were not significantly elevated in the supernatants of PBMC cultures of all seropositive monkeys as compared with all seronegative controls, IL2 levels were increased in a subset of 5 pairs. Increased constitutive cytokine release occurred in the absence of spontaneous proliferation. The increased constitutive release of IFNγ and IL2 suggests that STLV1 alters immune functions in infected but clinically healthy rhesus macaques and further characterizes STLV1 infection of rhesus macaques as a potential model for human HTLV1 infection.

Oxymorphone is a pure μ-opioid receptor agonist that is commonly used in nonhuman primate medicine and surgery to minimize pain ranging in intensity from moderate to severe. We compared pharmacokinetic profiles and physiologic and behavioral responses to oxymorphone between titi monkeys (Callicebus spp.) and rhesus macaques (Macaca mulatta). Titi monkeys (n = 4) and rhesus macaques (n = 4) were injected intravenously with either a bolus of 0.075 mg/kg oxymorphone or placebo on multiple occasions, with a minimal washout period of 14 d between trials. Blood collection was limited to no more than 3 samples per trial, with samples collected at multiple time points until 10 h after injection. Collection periods, animal order, and testing day were randomized. In addition, macaques underwent a single serial collection at all time points to validate study design. A 2-compartment model best described the disposition of oxymorphone in both species. Clearance was faster in macaques than titi monkeys, in which terminal half-life was longer. Statistically significant physiologic differences were found between species and between treatments within species. Apart from these effects, oxymorphone did not significantly change physiologic parameters over time. After oxymorphone treatment, macaques demonstrated behaviors reflecting pruritis, whereas titi monkeys exhibited sedation. Despite its mild side effects, we recommend the consideration of oxymorphone for pain management protocols in both Old and New World nonhuman primates.

Rhesus rhadinovirus (RRV) and retroperitoneal fibromatosis herpesvirus (RFHV), 2 closely related γ2 herpesviruses, are endemic in breeding populations of rhesus macaques at our institution. We previously reported significantly different prevalence levels, suggesting the transmission dynamics of RRV and RFHV differ with regard to viral shedding and infectivity. We designed a longitudinal study to further examine the previously observed differences between RRV and RFHV prevalence and the potential influence of age, season, and housing location on the same 90 rhesus macaques previously studied. Virus- and host-genome-specific real-time PCR assays were used to determine viral loads for both RRV and RFHV in blood and saliva samples collected at 6 time points over an 18-mo period. Proportions of positive animals and viral load in blood and saliva were compared between and within viruses by age group, location, and season by using 2-part longitudinal modeling with Bayesian inferences. Our results demonstrate that age and season are significant determinants, with age as the most significant factor analyzed, of viremia and oral shedding for both RRV and RFHV, and these pathogens exhibit distinctly different patterns of viremia and oral shedding over time within a single population.

Secondary hepatic amyloidosis in nonhuman primates carries a grave prognosis once animals become clinically ill. The purpose of this study was to establish serologic parameters that potentially could be used to identify rhesus macaques undergoing subclinical development of secondary hepatic amyloidosis. A retrospective analysis was completed by using serum biochemical profiles from 26 histologically diagnosed amyloidotic macaques evaluated at 2 stages of disease, clinical and subclinical (3 to 32 mo prior to clinical signs of disease). Standard serum biochemistry values for cases were compared with institutional age- and gender-specific references ranges by construction of 95% confidence intervals for the difference between means. In addition, 19 histologically diagnosed amyloidotic macaques and 19 age-matched controls were assayed for changes in various parameters by using routinely banked, frozen (-80 degrees C) sera available from clinical and subclinical time points. Clinically amyloidotic animals displayed increased levels of alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, gamma glutamyltranspeptidase, and macrophage colony-stimulating factor and significantly decreased quantities of albumin and total cholesterol. Subclinical amyloidotic animals displayed increased levels of alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, and serum amyloid A and decreased concentrations of albumin and total cholesterol. The serologic parameters studied indicate a temporal relationship of these factors not previously described, show a clear pattern of disease progression, and could be useful in subclinical disease detection.