Frequency of the major histocompatibility complex Mamu‐A*01 allele in experimental rhesus macaques in China

Background In Indian rhesus macaques, the major histocompatibility complex Mamu gene, especially the Mamu‐A*01 allele, plays an important role in simian immunodeficiency virus susceptibility and disease progression. The Mamu‐A*01 allele is one of the protective genes mostly being studied in simian acquired immunodeficiency syndrome. Methods PCR was used to amplify the Mamu‐A*01 allele in 130 Chinese‐origin rhesus macaques. Identification of the allele was then confirmed by sequencing and IFN‐γ ELISPOT assay. Results The Mamu‐A*01 allele was detected in 3.85% (5 of 130) of the experimental Chinese‐origin rhesus macaques. The sequence homology reached 99.1% in comparison with Indian rhesus macaques. A significantly large number of spots were observed in Mamu‐A*01‐positive monkeys when analyzed by ELISPOT with Gag181‐189 epitope stimulation. Conclusions Our study suggests that Mamu‐A*01‐positive Chinese‐origin rhesus monkeys are suitable for use in AIDS studies.     

Systemic arteriopathy in SIV-infected rhesus macaques (Macaca mulatta)

BACKGROUND: Severe disseminated vasculopathy was observed in two simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta). These animals developed clinical signs of AIDS, including lymphadenopathy, weight loss, diarrhea and collapse. RESULTS AND DISCUSSION: Grossly, both animals showed emaciation, lymphadenopathy, vegetations on the mitral valve, renal infarcts and a dilated intestine; one animal had multifocal hemorrhages in multiple organs. Histologically, both cases had disseminated arteriopathy characterized by intimal thickening and fibrosis with varying degrees of vasculitis. The lesion was prominent in the kidney, intestine, pancreas, liver, heart, lymph nodes, spleen and testis. Occasional venules had intimal thickening. Both cases had cytomegalovirus (CMV) infection with intranuclear inclusions, CMV antigen and nucleic acid; some inclusions were observed in endothelial cells within some of the vascular lesions in one of the two. These data suggest that CMV caused the unusual lesions.     

Comparison of virology and immunology in SHIV 89.6 proviral DNA and virus-inoculated rhesus macaques

Inoculation of cats, goats and monkeys with plasmids encoding full-length proviral genomes results in persistent lentiviral infections. This system could be used as a method for administration of an attenuated human immunodeficiency virus (HIV) vaccine. Here, we compare the virology and immunology in rhesus macaques inoculated with either simian/human immunodeficiency virus 89.6 (SHIV 89.6) virus or a plasmid containing the SHIV 89.6 proviral genome. There was a delay in appearance of systemic infection in DNA-inoculated animals compared with virus-inoculated animals, but otherwise the pattern of infection was similar. The serum immunoglobulin G anti-simian immunodeficiency virus (SIV) binding antibody response in DNA-inoculated animals was also delayed compared with virus-inoculated animals, but ultimately there was no difference between live virus and DNA-inoculation in the ability to induce the anti-SIV immune responses that were measured. Thus, the data support the concept that plasmid DNA encoding an attenuated virus could be used instead live virus for vaccination.     

Impact of internal and external factors on prosocial choices in rhesus macaques

While traditional economic models assume that agents are self-interested, humans and most non-human primates are social species. Therefore, many of decisions they make require the integration of information about other social agents. This study asks to what extent information about social status and the social context in which decisions are taken impact on reward-guided decisions in rhesus macaques. We tested 12 monkeys of varying dominance status in several experimental versions of a two-choice task in which reward could be delivered to self only, only another monkey, both the self and another monkey, or neither. Results showed dominant animals were more prone to make prosocial choices than subordinates, but only when the decision was between a reward for self only and a reward for both self and other. If the choice was between a reward for self only and a reward for other only, no animal expressed altruistic behaviour. Finally, prosocial choices were true social decisions as they were strikingly reduced when the social partner was replaced by a non-social object. These results showed that as in humans, rhesus macaques'' social decisions are adaptive and modulated by social status and the cost associated with being prosocial.This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.     

Differential distribution of antibodies to different viruses in young animals in the free-ranging rhesus macaques of Cayo Santiago

BACKGROUND: The breeding colony of free-ranging rhesus macaques was established in 1938 in Cayo Santiago (CS) with animals collected in northern India. The seroprevalence to cercopithecine herpesvirus type 1 (B virus) and simian retroviruses has been studied previously. RESULTS: This is the first report on the seropositivity to different viruses using samples collected shortly after removing animals (n = 245) from CS. All samples were negative for measles, simian immunodeficiency virus and simian type D retroviruses. The overall prevalence of antibodies was around 50% for simian T-lymphotropic virus I (STLV-I). For B virus, the prevalence was 38%. CONCLUSIONS: Data obtained showed marked differences in the antibody distribution to B virus and STLV-I within the free-ranging colony of rhesus macaques. Implication of these data for the Specific Pathogen Free program at the Caribbean Primate Research Center are also discussed.     

Effects of intestinal survival surgery on systemic and mucosal immune responses in SIV-infected rhesus macaques

Abstract: Evaluation of cellular immunity in the intestinal lamina propria of rhesus macaques has been used previously to assess protective immunity against mucosal simian immunodeficiency virus (SIV) challenges. As this technique requires survival surgery to obtain jejunal tissue, effects of surgical stress on the immune system were investigated. SIV-specific immune responses, including IgG and IgA binding antibodies in sera and mucosal secretions, IgG and IgA secreting cells in peripheral blood, IgG neutralizing antibodies, T-cell proliferative responses, and interferon-γ secretion by peripheral blood mononuclear cells, were evaluated pre- and post-surgery in macaques immunized with adenovirus-SIV recombinant vaccines and SIV envelope protein and in SIV-infected macaques. No differences in these immune parameters were observed in SIV-naïve, immunized macaques or healthy SIV-infected macaques with regard to surgery. A dramatic increase in total IgA antibody level following surgery in the rectal secretions of one SIV-infected macaque that was rapidly progressing to AIDS and failed to recover from surgery was attributed to an abscess that developed at the intestinal site. To date, nearly 30 other macaques have undergone the intestinal survival surgery, some on more than one occasion, without experiencing any clinical difficulty. Overall, our results suggest that in healthy macaques, intestinal resection survival surgery can be conducted safely. Further, the method can be used to reliably sample the intestinal mucosa without major or persistent impact on humoral or cellular immune responses.     

Age-dependent changes in T cell homeostasis and SIV load in sooty mangabeys

Sooty mangabeys ( Cercocebus atys ) showed age-dependent changes in T cell regeneration. Younger animals had a high percentage of CD4+ CD45RA+ T cells and a high concentration of T cell receptor excisional circles (TRECs) in peripheral blood, which indicated active thymopoiesis. In contrast, older animals had an increased T cell turnover, which suggested that most T cell production occurred in the periphery. In addition, the number of peripheral CD4+ T cells naturally decreased with age. Non-pathogenic SIVsm infection did not significantly change the T cell proliferation rate or the TREC concentration, though it did cause a moderate loss of peripheral CD4+ T cells. The viral load correlated negatively with age, which could be accounted for by the reduced availability of CD4+ target cells in older mangabeys. Thus, the number of susceptible target cells may be a limiting factor in natural SIV infection.     

Computed tomography or necropsy diagnosis of multiple bullae and the treatment of pneumothorax in rhesus macaques (Macaca mulatta)

Pulmonary bullae and pneumothorax have various etiologies in veterinary medicine. We diagnosed multiple pulmonary bullae combined with or without pneumothorax by computed tomography (CT) or necropsy in seven rhesus macaques (Macaca mulatta) imported from China. Two of seven rhesus macaques accompanied by pneumothorax were cured by fixation of ruptured lung through left or right 3rd intercostal thoracotomy. Pneumonyssus simicola, one of the etiologies of pulmonary bullae, was not detected from tracheobronchiolar lavage. To the best of our knowledge, this is the first case report on the CT‐aided diagnosis of pulmonary bullae and the successful treatment of combined pneumothorax by thoracotomy in non‐human primates (NHPs).     

Evidence for a lentiviral etiology in an epizootic of immune deficiency and lymphoma in stump-tailed macaques (Macaca arctoides).

A retrospective study determined that an epizootic of immune suppression and lymphoma in stump-tailed macaques (Macaca arctoides) that began in 1976 was associated with a horizontally spread lentivirus infection. This conclusion was based on serology, epidemiology, pathology, and virus isolation. The lesions found in the stump-tailed macaques were more compatible with lesions seen in SIV-infected rhesus than those seen in rhesus macaques infected with type D retroviruses. A lentivirus, isolated from a rhesus inoculated with lymph node homogenate from a stump-tailed macaque, was designed SIVstm and was pathogenic for rhesus macaques. The isolate was antigenically related to other SIVs as well as to HIV-1 and HIV-2. Two surviving stump-tailed macaques sent to another colony carried SIVstm latently for at least 7 years and disseminated it throughout that colony.     

Up-regulation of glutamate concentration in the putamen and in the prefrontal cortex of asymptomatic SIVmac251-infected macaques without major brain involvement

We quantified putamen and prefrontal cortex metabolites in macaques with simian immunodeficiency virus infection and searched for virological and histological correlates. Fourteen asymptomatic macaques infected since 8-78 months (median: 38) were compared with eight uninfected ones. Absolute concentrations of acetate, alanine, aspartate, choline, creatine, GABA, glutamate, glutamine, lactate, myo-inositol, N-acetylaspartate, taurine and valine were determined by ex vivo proton magnetic resonance spectroscopy. Glutamate concentration in the CSF was determined by HPLC. Gliosis was assessed by glial fibrillary acidic protein and CD68 immunohistochemistry. Glutamate concentration was slightly increased in the prefrontal cortex (19%, p = 0.0152, t-test) and putamen (13%, p = 0.0354, t-test) of the infected macaques, and was unaffected in the CSF. Myo-inositol concentration was increased in the prefrontal cortex only (27%, p = 0.0136). The concentrations of glutamate and myo-inositol in the prefrontal cortex were higher in the animals with marked or intense microgliosis (p = 0.0114). The other studied metabolites, including N-acetylaspartate, were not altered. Glutamate concentration may thus increase in the cerebral parenchyma in asymptomatic animals, but is not accompanied by a detectable decrease in N-acetylaspartate concentration (neuronal dysfunction). Thus, there are probably compensatory mechanisms that may limit glutamate increase and/or counterbalance its effects.     

Pathogenic analysis of coxsackievirus A10 in rhesus macaques

Coxsackievirus A10 (CV-A10) is one of the etiological agents associated with hand, foot and mouth disease (HFMD) and also causes a variety of illnesses in humans, including pneumonia, and myocarditis. Different people, particularly young children, may have different immunological responses to infection. Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus. The characteristics of CV-A10 infection, replication, and shedding in humans remain unknown. In this study, rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans. The clinical symptoms, viral shedding, inflammatory response and pathologic changes were investigated in acute infection (1–11 day post infection) and recovery period (12–180 day post infection). All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans. Substantial inflammatory pathological damages were observed in multi-organs, including the lung, heart, liver, and kidney. During the acute period, all rhesus macaques displayed clinical signs, viral shedding, normalization of serum cytokines, and increased serum neutralizing antibodies, whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period. In addition, there were no significant differences between respiratory and digestive tract infected animals. Overall, all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 pathophysiology and assessing the development of potential human therapies.     

Interleukin-1 induces sleep-like behavior and alters call structure in juvenile rhesus macaques

To date, there have been no investigations of the behavioral effects of interleukin-1 (IL-1) in nonhuman primates. In this study the locomotor behavior and vocalizations of juvenile rhesus monkeys were monitored for 45 minutes following intravenous injections of recombinant human IL-1 alpha. In addition, their reaction to a broadcasted recording of infant monkey distress calls was determined 20 minutes after the beginning of each test session. IL-1 induced sleep-like inactivity and significantly diminished the monkey's behavioral and vocal responses to the broadcasted calls. The coo calls uttered by the monkeys following IL-1 treatment also had a longer duration and lower fundamental frequency than calls during the control condition. As several studies have indicated that behavioral effects of IL-1 may be mediated by corticotropin-releasing hormone (CRH), a second group of rhesus monkeys was given injections of CRH. CRH did not alter behavior or call structure at the dose administered. These results extend previous research on the behavioral effects of IL-1 to include the nonhuman primate and provide the first evidence that cytokines can affect vocal communication in rhesus monkeys. © 1995 Wiley-Liss, Inc.     

人工饲养中国猕猴中SRV、STLV和BV的流行病学调查

非人灵长类动物是十分重要的生物医学资源。由于与人类在生理生化、免疫、遗传等方面近似,猕猴是重要的非人灵长类实验动物之一。然而,猕猴作为自然宿主,易感染D型逆转录病毒(simian type D retrovirus,SRV)和T淋巴细胞白血病病毒(simian T lymphotropic virus,STLV)这两种逆转录病毒,并可能会影响AIDS猕猴动物模型等的研究结果。猴B病毒(ceropithecine herpesvirus1,BV)对猕猴及动物从业人员均有危害。云南省拥有较大规模的中国猕猴繁殖种群。基于以上原因,建立SPF级别的中国猕猴种群十分必要。该文应用PCR技术筛查了人工饲养种群中411只中国猕猴的SRV、STLV和BV感染流行情况。结果表明:SRV、STLV和BV的阳性感染率分别为19.71%(81/411)、13.38%(55/411)和23.11%(95/411)。同时比较分析了不同性别及年龄组中国猕猴的病毒感染情况。该研究将有助于建立SPF级别的中国猕猴繁殖种群。