Two gammaherpesviruses, Epstein-Barr virus (EBV) (Lymphocryptovirus genus) and Kaposi's sarcoma-associated herpesvirus (KSHV) (Rhadinovirus genus) have been implicated in the etiology of AIDS-associated lymphomas. Homologs of these viruses have been identified in macaques and other non-human primates. In order to assess the association of these viruses with non-human primate disease, archived lymphoma samples were screened for the presence of macaque lymphocryptovirus (LCV) homologs of EBV, and macaque rhadinoviruses belonging to the RV1 lineage of KSHV homologs or the more distant RV2 lineage of Old World primate rhadinoviruses. Viral loads were determined by QPCR and infected cells were identified by immunolabeling for different viral proteins. The lymphomas segregated into three groups. The first group (n = 6) was associated with SIV/SHIV infections, contained high levels of LCV (1–25 genomes/cell) and expressed the B-cell antigens CD20 or BLA.36. A strong EBNA-2 signal was detected in the nuclei of the neoplastic cells in one of the LCV-high lymphomas, indicative of a type III latency stage. None of the lymphomas in this group stained for the LCV viral capsid antigen (VCA) lytic marker. The second group (n = 5) was associated with D-type simian retrovirus-2 (SRV-2) infections, contained high levels of RV2 rhadinovirus (9–790 genomes/cell) and expressed the CD3 T-cell marker. The third group (n = 3) was associated with SIV/SHIV infections, contained high levels of RV2 rhadinovirus (2–260 genomes/cell) and was negative for both CD20 and CD3. In both the CD3-positive and CD3/CD20-negative lymphomas, the neoplastic cells stained strongly for markers of RV2 lytic replication. None of the lymphomas had detectable levels of retroperitoneal fibromatosis herpesvirus (RFHV), the macaque RV1 homolog of KSHV. Our data suggest etiological roles for both lymphocryptoviruses and RV2 rhadinoviruses in the development of simian AIDS-associated lymphomas and indicate that the virus-infected neoplastic lymphoid cells are derived from different lymphocyte lineages and differentiation stages.

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Morphine has long been known to have immunosuppressive properties in vivo, but the molecular and immunologic changes induced by it are incompletely understood. To explore how these changes interact with lentiviral infections in vivo, animals from two nonhuman primate species (African green monkeys and pigtailed macaques) were provided morphine and studied using a systems biology approach. Biological specimens were obtained from multiple sources (e.g. lymph node, colon, cerebrospinal fluid, and peripheral blood) before and after the administration of morphine (titrated up to a maximum dose of 5 mg/kg over a period of 20 days). Cellular immune, plasma cytokine, and proteome changes were measured and morphine-induced changes in these parameters were assessed on an interorgan, interindividual, and interspecies basis. In both species, morphine was associated with decreased levels of Ki-67 ؉ T-cell activation but with only minimal changes in overall T-cell counts, neutrophil counts, and NK cell counts. Although changes in T-cell maturation were observed, these varied across the various tissue/ fluid compartments studied. Proteomic analysis revealed a morphine-induced suppressive effect in lymph nodes, with decreased abundance of protein mediators involved in the functional categories of energy metabolism, signaling, and maintenance of cell structure. These findings have direct relevance for understanding the impact of heroin addiction and the opioids used to treat addiction as well as on the potential interplay between opioid abuse and the immunological response to an infective agent. Molecular & Cellular

Abstract. A 2.5-year-old captive female mandrill (Papio sphinx) died following a protracted course of intermittent abdominal bloat, diarrhea, and severe weight loss. Necropsy revealed emaciation and marked gastrointestinal distention with gas and ingesta. Histologic evaluation revealed severe diffuse granulomatous enterocolitis and mesenteric lymphadenitis with massive numbers of 1-2-m acid-fast bacilli within macrophages. Additionally, there was moderate to severe multifocal myocardial and vascular amyloidosis, moderate multifocal pyogranulomatous interstitial pneumonia with no acid-fast bacteria, and moderate multifocal glossal candidiasis. Samples of feces, ileum, and colon were positive for Mycobacterium avium subsp. paratuberculosis by radiometric culture and a polymerase chain reaction-amplified DNA probe specific for the insertion sequence IS900 of this organism.Paratuberculosis (Johne's disease) is a chronic progressive granulomatous intestinal disease of wild and domestic ruminants with a worldwide distribution. 1-3 The disease is caused by infection with Mycobacterium avium subsp. paratuberculosis, an acid-fast, weakly gram-positive bacillus. 2,3 Experimental infections with this organism have been produced in pigs, horses, pigeons, chickens, and laboratory animals including mice, hamsters, guinea pigs, and rabbits. 1,3,5,[6][7][8][9]11,12,14 One report of naturally occurring confirmed paratuberculosis in nonhuman primates has been described in the literature. 10 The outbreak affected 29 of 38 individuals in a colony of stumptail macaques (Macaca arctoides). The clinical and pathologic features of paratuberculosis in this species were comparable with those reported for paratuberculosis in ruminants and M. a. subsp. avium infections in primates. In recent years, M. a. paratuberculosis has also been implicated as a possible cause of Crohn's disease in humans, although a causal relationship has not been definitively established. 1,2,13 This report documents a case of paratuberculosis in a mandrill (Papio sphinx).A 21-month-old intact female mandrill arrived at Lincoln Park Zoo, Chicago, Illinois, and was placed in 30-day quarantine. Routine physical examination, thoracic and abdominal radiographs, a serum chemistry profile, and a complete blood count were within normal limits. An intradermal tuberculin test and fecal cultures for enteric pathogens including Campylobacter sp. and Salmonella spp. were negative. Serology was reported as negative for herpesvirus SA8, Herpes simiae (Herpes B), measles, simian immunodeficiency virus, simian retroviruses (1, 2, and 5), simian T-cell leu- kemia virus-1, and encephalomyocarditis virus, while positive for cytomegalovirus. Approximately 2 months after arrival, this individual developed intermittent watery diarrhea, abdominal bloat, and progressive weight loss. The animal's condition continued to decline in spite of enhanced caloric supplementation via nasogastric tube in advanced stages of disease. Death occurred shortly after exploratory surgery was performed 7 mon...