ALBERT

Beschreibung: Overall, diseases of the vascular system are rarely observed entities among nonhuman primates that are commonly associated with systemic infections, septicemia or bacteremia. Rhesus monkeys infected with simian immunodeficiency virus (SIV) may develop a chronic occlusive arteriopathy of unknown etiology in late stages of the disease. This SIV associated arteriopathy is the only well-known specific vascular entity described in nonhuman primates. We herein report a unique case of granulomatous arteritis in a grey mouse lemur affecting multiple organs, which is not comparable to other disease entities formerly described in nonhuman primates. The features of the entity most closely resemble disseminated visceral giant cell arteritis in humans. A concise description of the disease is given, and the differential diagnoses are discussed. An idiopathic pathogenesis is suspected.

Beschreibung: Endometriosis is a poorly understood common debilitating women's reproductive disorder resulting from proliferative and ectopic endometrial tissue associated with variable clinical symptoms including dysmenorrhea (painful menstrual periods), dyspareunia (pain on intercourse), female infertility, and an increased risk of malignant transformation. The rhesus macaque (Macaca mulatta) develops a spontaneous endometriosis that is very similar to that seen in women. We hypothesized that specific major histocompatibility complex (MHC) alleles may contribute to the pathogenesis of endometriosis. As part of a collaboration between the Biomedical Primate Research Centre (BPRC) in the Netherlands and the New England Primate Research Center (NEPRC) in the United States, we analyzed DNA sequences of MHC class I (Macaca mulatta, Mamu-A1) and class II (Mamu-DRB) alleles from rhesus macaques with endometriosis and compared the allele frequencies with those of age-matched healthy macaques. We demonstrate that two MHC class I alleles are overrepresented in diseased macaques compared to controls: Mamu-A1*001, 33.3 % in BPRC animals with endometriosis vs. 11.6 % in healthy macaques (p =  0.007), and Mamu-A1*007, 21.9 % NEPRC rhesus macaques vs. 6.7 %, (p =  0.003). We provide evidence that select MHC class I alleles are associated with endometriosis in rhesus macaques and suggest that the disease pathogenesis contribution of MHC class I warrants further research.

Beschreibung: Several cases of spontaneous endometriosis in middle-aged to old rhesus macaques (Macaca mulatta) from the breeding colony of the German Primate Center were thoroughly characterized with regards to anatomical distribution and macroscopic appearance, histological differentiation and immunohistochemical profile including somatic markers, hormonal receptors, and proliferation indices. More than half of the examined animals (five of nine) were directly related to one breeding male, supporting a strong genetic predisposition. Histologically, four different types of endometriotic lesions, depending on the degree of ectopic endometrial gland and stromal differentiation (well differentiated, purely stromal, mixed differentiation, poorly differentiated), could be constantly identified within all animals. Immunohistochemistry (IHC) of cytokeratin (CK), vimentin, smooth muscle actin (SMA), desmin, estrogen (ER), and progesterone (PR) receptors as well as of the nuclear proteins Ki67 and p53 revealed varying staining patterns in the four different types of endometriosis differentiation and compared to normal endometrium. Purely stromal, mixed, or poorly differentiated lesions, especially, showed additional cytokeratin-positive stromal cells, whereas epithelial cells of endometriosis with mixed or poor differentiation increasingly expressed mesenchymal markers (vimentin, SMA). Hormonal receptor and Ki67 expression in well-differentiated endometriotic lesions mostly reflected that of normal endometrial tissue according to the cyclic phase of the animal, while the expression gradually diminished with decreasing grade of differentiation. However, increased nuclear accumulations of p53 antigen could only be continuously detected in epithelial cells of mixed or poorly differentiated endometriosis. Altogether, these findings support the pathogenetic theory of coelomic metaplasia, since the expression profiles of somatic markers in less differentiated forms closely resembled that of mesothelial cells. Thus, the four different histological types of endometriosis might display subsequent grades of differentiation in the course of time, with poorly differentiated types representing newly formed, immature lesions and well-differentiated types being older, fully differentiated forms, rather than being the outcome of dedifferentiation processes.

Beschreibung: Human immunodeficiency virus (HIV) comorbidities have become clinically more important due to antiretroviral therapy. Although therapy increases life expectancy, it does not completely suppress immune activation and its associated complications. The simian immunodeficiency virus (SIV)-infected rhesus macaque (Macaca mulatta) represents a valuable model for the investigation of SIV-associated diseases. Although cardiovascular (CV) changes are common in HIV-infected patients, there are only a few reports on the incidence of CV findings in SIV-infected animals. In addition, potential associations between pathohistological findings and hematological parameters are still unclear. We therefore conducted a retrospective analysis of 195 SIV-infected rhesus macaques that were euthanized with AIDS-related symptoms at the German Primate Center, Goettingen, over a 25-year period. Pathological findings were correlated with hematological data. The main findings included myocarditis (12.8 %), endocarditis (9.7 %), and arteriopathy (10.3 %) in various organs. Thrombocytopenia occurred more frequently in macaques with endocarditis or arteriopathy than in macaques without CV disease (80 % in animals with endocarditis, 60 % in animals with arteriopathy, p 

Beschreibung: We report observations on fur-rubbing with leaves from Piper aduncum by a San Martín titi monkey, Callicebus oenanthe. Fur-rubbing occurred during the transition from the dry to the rainy season in a titi monkey group living in a forest fragment in the Moyobamba region of Peru. Since Piper leaves include very potent compounds that may affect ectoparasites, we tentatively interpret the observed fur-rubbing as self-medication.

Beschreibung: Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs). These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys) are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs) are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28) during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of human fertility preservation strategies.

Beschreibung: In times of increasing costs for health insurances, obstructive lung diseases are a burden for both the patients and the economy. Pulmonary symptoms of asthma and chronic obstructive pulmonary disease (COPD) are similar; nevertheless, the diseases differ in pathophysiology and therapeutic approaches. Novel therapeutics are continuously developed, and nonhuman primates (NHPs) provide valuable models for investigating novel biologicals regarding efficacy and safety.This review discusses the role of nonhuman primate models for drug development in asthma and COPD and investigates whether alternative methods are able to prevent animal experiments.

Beschreibung: Daily travel distance (DTD), the distance an animal moves over the course of the day, is an important metric in movement ecology. It provides data with which to test hypotheses related to energetics and behaviour, e.g. impact of group size or food distribution on DTDs. The automated tracking of movements by applying GPS technology has become widely available and easy to implement. However, due to battery duration constraints, it is necessary to select a tracking-time resolution, which inevitably introduces an underestimation of the true underlying path distance. Here we give a quantification of this inherent systematic underestimation of DTDs for a terrestrial primate, the Guinea baboon. We show that sampling protocols with interval lengths from 1 to 120 min underestimate DTDs on average by 7 to 35 %. For longer time intervals (i.e. 60, 90, 120 min), the relative increase of deviation from the true trajectory is less pronounced than for shorter intervals. Our study provides first hints on the magnitude of error, which can be applied as a corrective when estimating absolute DTDs in calculations on travelling costs in terrestrial primates.

Beschreibung: Inter- and intra-specific variation in the propensity to form coalitions has been explained by variation in the availability of suitable partners, distribution of fighting ability, coalition profitability, and costs of coordination. Male coalition formation can be an alternative reproductive strategy to one-on-one competition to maximize male reproductive success. Here we focus on age as a state variable to explain within-group variation in individual propensity to form coalitions against other group members. We specifically test the prediction that males conditionally switch from a solo strategy for achievement of high mating success to a cooperative strategy after reaching post-prime age in male Barbary macaques (Macaca sylvanus). We combined new observations with data collected in 2006 and 2008 on the same individuals from one captive group living in semi-natural conditions at Affenberg Salem, Germany, and found that in all years males between 5 and 13 years formed significantly fewer coalitions than males 14 years and older (post-prime). More importantly, we found those males that aged into the post-prime phase to have switched their reproductive strategy and to form significantly more coalitions in 2014 compared to 2008. These first longitudinal data together with earlier cross-sectional analyses in this and other primate species suggest that group-level measures of coalition propensity may be strongly affected by the age composition of groups and that male coalition formation can be a conditional reproductive strategy.

Beschreibung: Herpes B virus (BV) infection is highly prevalent among adult Asian macaques and rarely causes severe disease in infected animals. In contrast, BV infection of humans can induce fatal encephalitis in the absence of treatment. Therefore, the development of diagnostic tests for specific and sensitive detection of antibodies against BV is an important task. The cross-reactivity of antibodies against BV with related simplex viruses of other primates may afford an opportunity to obtain sensitive detection systems without the need to work with the highly pathogenic BV. Moreover, it has been proposed that use of recombinant viral glycoproteins may allow for a detection of antibody responses against BV with high specificity. However, limited data are available for both approaches to BV diagnostic. Here, we report that simian agent 8 (SA8; infects African green monkeys)- and herpesvirus papio 2 (HVP-2; infects baboons)-infected cells allow for a more sensitive detection of antibody responses against BV in macaques than lysates of herpes simplex virus type 1 and 2 (HSV-1/2; infect humans)-infected cells and a commercial HSV ELISA (Enzygnost® Anti-HSV/IgG). In addition, we show that sera from BV-infected macaques frequently contain antibodies against the recombinant BV glycoprotein gD (BV gD) that has been previously proposed as a diagnostic target for discriminating BV- and HSV-induced antibodies. However, we found that antibodies of some HSV-infected human patients also reacted with BV gD. In contrast, only sera of HSV-1- and HSV-2-infected humans, but not sera from BV-infected macaques, reacted with HSV-1/2 gG. Collectively, these results suggest that both SA8 and HVP-2 allow for sensitive and comparable detection of BV-directed antibody responses in macaques and that the combination of BV gD and HSV-1/2 gG needs to be complemented by a least one additional viral glycoprotein for reliable discrimination between antibody responses against BV and HSV-1/2 in humans.

Beschreibung: Guillain-Barré syndrome (GBS) is a rare, mainly acute inflammatory polyneuropathy in humans. It is frequently post-infectious with auto antibodies being formed against myelin sheaths, resulting in a progressive and more-or-less severe paralysis of the motor neuron and cranial nerves. Mortality is low and 60 % of the patients recover completely from the disease after intensive treatment.In animals, there are a few diseases that closely resemble GBS, but cases of GBS in monkeys seem to be scarce. In this case report, the clinical course of a progressive tetraplegia in a male rhesus macaque is described. Clinical, cerebrospinal fluid (CSF), electroneurography (ENG) and electromyography (EMG), and pathological findings revealed symptoms very similar to human GBS.

Beschreibung: A 9-year-old female captive patas monkey (Erythrocebus patas) presented with poor general condition, inability to stand, petechiae, anaemia, thrombocytopenia, and leukocytosis. Due to poor response to treatment, the animal was euthanized 16 days later. Postmortem examination revealed hemorrhages in several organs and bilateral cerebral infarctions. Histologically, prominent accumulations of large neoplastic lymphocytes in cerebral and meningeal blood vessels were demonstrated within the lesions and in other organs (e.g., bone marrow, ovary, intestine). Immunohistochemically, neoplastic cells expressed CD3 and Ki-67. PCR revealed a lymphocryptovirus (LCV) infection, while Epstein–Barr nuclear antigen 2 (EBNA2) could not be demonstrated within neoplastic cells by means of immunohistochemistry. Based on the pathological findings, an intravascular lymphoma (IVL) of T-cell origin was diagnosed. To the authors' knowledge, this is the first report on this rare entity in a nonhuman primate.

Beschreibung: Spontaneous cholelithiasis was found in a male African green monkey (Chlorocebus aethiops) at necropsy. Choleliths varied in size, shape and colour. Gallstones were analysed using accepted analytical methods. Results showed that the gallstones were composed of cholesterol and protein in varying proportions. Histologically, the gallbladder showed diffuse mild to moderate lymphocytic infiltration. The etiology of the cholelithiasis in the examined individual remains unknown.

Beschreibung: In a landscape fragmented by agriculture, the extent to which forest-dwelling primates can use the matrix between fragments can be critical for their long-term survival. So far, the golden-headed lion tamarin (Leontopithecus chrysomelas), an endangered primate inhabiting the Atlantic Forest of south Bahia, is only known to use shaded cacao (Theobroma cacao) agroforests within the matrix. We report on the use of a rubber plantation by a group of golden-headed lion tamarins between August 2013 and January 2014. The group used the rubber plantation on 16 of the 22 observation days (73 %), and we recorded behaviours such as eating, grooming and sleeping, consistent with the use of the area as a home range. We also observed associations with Wied's marmosets (Callithrix kuhlii). The locations of group sightings were not uniformly spread across the entire area of the rubber plantation, suggesting preferred use of certain areas. The presence of resources such as jackfruits (Artocarpus heterophyllus) and epiphytic bromeliads may be attracting both species to these plantations. In addition to shaded cacao plantations, rubber plantations with the appropriate structure may be a viable option for increasing forest connectivity for both species in south Bahia, reconciling economic rubber production with primate conservation.

Beschreibung: In this paper we report on two encounters between olive baboons (Papio anubis) and crowned eagles (Stephanoaetus coronatus) at Lake Manyara National Park, northern Tanzania. During these encounters olive baboons responded by giving alarm calls and all infants and juveniles rushed down from trees seeking cover under bushes or close proximity to adult conspecifics. In one of the events, alarm calls from banded mongoose (Mungos mungo) and rock hyraxes (Procavia capensis) most likely triggered alarm calling of vervet monkeys (Chlorocebus pygerythrus) which in turn prompted baboons to respond with alarm calls as well. In both observations, adult male baboons took the lead in climbing trees, threatening the eagle (staring, yawning, ground slapping) and chasing it away. The reaction of the baboons suggests that crowned eagles pose a threat at least for juvenile baboons at Lake Manyara National Park.

Beschreibung: To safeguard patients, regulatory authorities require that new drugs that are to be given by the intravitreal (IVT) route are assessed for their safety in a laboratory species using the same route of administration. Due to the high similarity of ocular morphology and physiology between humans and nonhuman primates (NHPs) and due to the species specificity of many biotherapeutics, the monkey is often the only appropriate model. To this end, intravitreal administration and assessment of ocular toxicity are well established in cynomolgus monkeys (Macaca fascicularis). In contrast, the common marmoset monkey (Callithrix jacchus) is not a standard model for ocular toxicity studies due to its general sensitivity to laboratory investigations and small eye size. It was the purpose of the present work to study whether the marmoset is a useful alternative to the cynomolgus monkey for use in intravitreal toxicological studies. Six marmoset monkeys received repeated (every 2 weeks for a total of four doses) intravitreal injections of 10 or 20 µL of a placebo. The animals were assessed for measurements of intraocular pressure (IOP), standard ophthalmological investigations and electroretinography (ERG). At the end of the dosing period, the animals were sacrificed and the eyes were evaluated histologically. ERG revealed similar results when comparing predose to end-of-study data, and there was no difference between the two dose volumes. A transient increase in the IOP was seen immediately after dosing, which was more pronounced after dosing of 20 µL compared to 10 µL. Ophthalmologic and microscopic observations did not show any significant changes. Therefore, it can be concluded that 10 µL as well as 20 µL intravitreal injections of a placebo are well tolerated in the marmoset. These results demonstrate that the common marmoset is an alternative to the cynomolgus monkey for intravitreal toxicity testing.

Beschreibung: Induced pluripotent stem cells (iPS cells) generated by cellular reprogramming from nonhuman primates (NHPs) are of great significance for regenerative medicine and for comparative biology. Autologously derived stem cells would theoretically avoid any risk of rejection due to host–donor mismatch and may bypass the need for immune suppression post-transplant. In order for these possibilities to be realized, reprogramming methodologies that were initially developed mainly for human cells must be translated to NHPs. NHP studies have typically used pluripotent cells generated from young animals and thus risk overlooking complications that may arise from generating iPS cells from donors of other ages. When reprogramming is extended to a wide range of NHP species, available donors may be middle- or old-aged. Here we have pursued these questions by generating iPS cells from donors across the life span of the common marmoset (Callithrix jacchus) and then subjecting them to a directed neural differentiation protocol. The differentiation potential of different clonal cell lines was assessed using the quantitative polymerase chain reaction. The results show that cells derived from older donors often showed less neural marker induction. These deficits were rescued by a 24 h pretreatment of the cells with 0.5 % dimethyl sulfoxide. Another NHP that plays a key role in biological research is the chimpanzee (Pan troglodytes). iPS cells generated from the chimpanzee can be of great interest in comparative in vitro studies. We investigated if similar deficits in differentiation potential might arise in chimpanzee iPS cells reprogrammed using various technologies. The results show that, while some deficits were observed in iPS cell clones generated using three different technologies, there was no clear association with the vector used. These deficits in differentiation were also prevented by a 24 h pretreatment with 0.5 % dimethyl sulfoxide.

Beschreibung: This special issue about selected diseases of nonhuman primates was created in honor of Franz-Josef Kaup, who worked as a primate pathologist at the German Primate Center (DPZ) for 25 years. In 1992, Franz-Josef Kaup started his career at the DPZ as head of the working group Experimental Pathology. Prior to that he worked as a research assistant in the division Electron Microscopy at the Institute of Pathology of the University of Veterinary Medicine in Hanover. He was very experienced in the field of electron microscopy and used this expertise to establish a central electron microscopy laboratory at the DPZ. In the beginning, research of the working group Experimental Pathology was focused on gastrointestinal and respiratory infections and was closely related to projects of the Department of Virology. At that time, experimental infections of rhesus macaques with simian immunodeficiency virus (SIV) and associated opportunistic infections became the main subject of his research. The contribution of Christiane Stahl-Hennig and coauthors about SIV-induced cardiovascular diseases reflects the still ongoing collaboration in this research field. After merging the Experimental Pathology and Primate Husbandry in 1996, Franz-Josef Kaup headed the newly created Department of Veterinary Medicine and Primate Husbandry. This department became the central service unit of the DPZ in 1999 and offered a broad spectrum of services in veterinary diagnostics, primate husbandry, and animal welfare, which was intensively used by many internal and external scientists. In 2001, Walter Bodemer joined the group and the scientific contents expanded with a new focus on the pathogenesis of prion diseases. Some important aspects of this era are summarized in the work of Walter Bodemer.

Beschreibung: The protein c-CBL is a ubiquitin ligase. It catalyzes the last step of the transfer of ubiquitin to target proteins. Upon completion of polyubiquitination, the target proteins are degraded. Clinically, it is important that c-CBL is mutated in a subset of patients who develop myeloid malignancies, which are diseases of the hematopoietic stem or progenitor cells. c-CBL has also been shown to be expressed by human spermatogonia. The whole spermatogonial cell population possesses a subset that comprises also the spermatogonial stem cells. Based on these findings we hypothesized that c-CBL might be a general stem cell marker. To test this, we first validated the antibody using marmoset bone marrow and adult testis. In both tissues, the expected staining pattern was observed. Western blot analysis revealed only one band of the expected size. Then, we examined the expression of c-CBL in marmoset monkey embryonic stem (ES) cells, induced pluripotent stem (iPS) cells and adult stem cells. We found that c-CBL is strongly expressed in undifferentiated marmoset iPS cells and ES cells. However, adult stem cells in the gut and the stomach did not express c-CBL, indicating that c-CBL is not a general stem cell marker. In summary, c-CBL is strongly expressed in pluripotent stem cells of the marmoset monkey as well as in selected adult stem cell types. Future studies will define the function of c-CBL in pluripotent stem cells.

Beschreibung: Mouse lemurs, the world's smallest primates, inhabit forests in Madagascar. They are nocturnal, arboreal and dependent on vision for their everyday lives. In the last decades, the grey mouse lemur became increasingly important for biomedical research, in particular aging research. Experiments which require the combination of visual fitness and old age consequently depend on a solid knowledge of ocular pathologies. Although ocular diseases in mouse lemurs have been described as being common, they have not received much attention so far. Yet it is important to know when and why ocular diseases in captive mouse lemurs may occur. This review aims to provide a comprehensive overview of known ocular findings in mouse lemurs. It summarizes the frequency of ocular findings in captive mouse lemur colonies and points to their likely causes and treatment options based on the evidence available from other animals and humans. In addition, it shall be discussed whether age or genetic background may affect their development. This review may be used as a reference for future studies which require an assessment of visual performance in mouse lemurs and help to evaluate observed clinical signs and ocular diseases. Furthermore, the high incidence of specific diseases may provide new perspectives and set the groundwork for a new animal model for ocular research.

Beschreibung: Data on spontaneous pathology are substantially scarce for common marmosets, compared to other laboratory animals, but is essential for the interpretation of histological findings in the context of toxicological and experimental studies. Especially if common marmosets are used as experimental animals in respiratory research, detailed knowledge on the spectrum, occurrence, and incidence of spontaneous histopathological pulmonary lesions in this non-human primate species is required. In this study, lung tissue of 638 common marmosets from the marmoset colony of the German Primate Center was examined histologically. The analysis revealed a high incidence of predominantly mild and multifocal interstitial pneumonia (32.99 %) of unknown etiology in most cases. Only few marmosets exhibited lobar pneumonia (1.41 %) and bronchopneumonia (0.94), which were mainly caused by bacterial pathogens such as Bordetella bronchiseptica and Klebsiella pneumoniae. Lung immaturity and atelectasis were common histological findings in newborn marmosets. Typical background lesions included anthracosis (8.15 %), hemosiderosis (1.72 %), extramedullary hematopoiesis (11.6 %), mineralization (10.97 %), and inflammatory cell foci (10.34 %). In addition, three cases of pulmonary arteriopathy (0.47 %) and 1 case of foreign-body granuloma (0.16 %) were detected in the marmoset study cohort. The high prevalence of circulatory disturbances (congestion, edema, hemorrhage) and changes in air content (secondary atelectasis, alveolar emphysema) could partly be explained by euthanasia-related artifacts or agonal changes. The present study provides a comprehensive overview of the range and incidence of spontaneous pulmonary histopathology in common marmosets, serving as valuable reference data for the interpretation of lung lesions in toxicological and experimental marmoset studies.

Beschreibung: Humans and African great apes (AGAs) are naturally infected with several species of closely related malaria parasites. The need to understand the origins of human malaria as well as the risk of zoonotic transmissions and emergence of new malaria strains in human populations has markedly encouraged research on great ape Plasmodium parasites. Progress in the use of non-invasive methods has rendered investigations into wild ape populations possible. Present knowledge is mainly focused on parasite diversity and phylogeny, with still large gaps to fill on malaria parasite ecology. Understanding what malaria infection means in terms of great ape health is also an important, but challenging avenue of research and has been subject to relatively few research efforts so far. This paper reviews current knowledge on African great ape malaria and identifies gaps and future research perspectives.

Beschreibung: In order to calibrate stem cell exploitation for cellular therapy in neurodegenerative diseases, fundamental and preclinical research in NHP (nonhuman primate) models is crucial. Indeed, it is consensually recognized that it is not possible to directly extrapolate results obtained in rodent models to human patients. A large diversity of neurological pathologies should benefit from cellular therapy based on neural differentiation of stem cells. In the context of this special issue of Primate Biology on NHP stem cells, we describe past and recent advances on cell replacement in the NHP model of Parkinson's disease (PD). From the different grafting procedures to the various cell types transplanted, we review here diverse approaches for cell-replacement therapy and their related therapeutic potential on behavior and function in the NHP model of PD.

Beschreibung: This study was undertaken to investigate the susceptibility of rhesus monkeys to the calpox virus, an orthopoxvirus (OPXV) of the Cowpox virus species (CPXV), which is uniformly lethal in common marmosets. Six rhesus monkeys were either intravenously (i.v.) or intranasally (i.n.) exposed to the virus. Monitoring of the macaques after viral exposure included physical examinations, the determination of viral load by real-time PCR and plaque assay, and the analysis of humoral responses. Two i.v. inoculated animals developed numerous classical pox lesions that started after inoculation at days 7 and 10. Both animals became viremic and seroconverted. They exhibited maximal numbers of lesions of approximately 50 and 140 by day 21. One animal completely recovered, while the other one suffered from a phlegmonous inflammation of a leg initially induced by a secondarily infected pox lesion and was euthanized for animal welfare reasons. In contrast to previous pathogenicity studies with the calpox virus in marmosets, none of the four animals inoculated intranasally with doses of the calpox virus exceeding those used in marmosets by orders of magnitude showed typical clinical symptoms. No viral DNA was detectable in the blood of those animals, but three animals seroconverted. In two of these three animals, infectious virus was sporadically isolated from saliva. This indicates that rhesus monkeys are less susceptible to calpox virus infection, which limits their use in further intervention studies with OPXV.