California Primate Research Center Research Articles

Why are infants so attractive to others? The form and function of infant handling in bonnet macaques

Female macaques and baboons are intensely interested in other females’ infants, but provide little direct care for them. The selective factors that shape this strong attraction to neonates may differ from those that shape alloparental care in other taxa. The attraction to neonates may have evolved because (1) it enhances young females’ acquisition of maternal skills, (2) it is a form of reproductive competition among females, or (3) it is a by-product of selection for appropriate maternal care. I studied patterns of infant handling in a large group of bonnet macaques,Macaca radiata, at the California Primate Research Center at the University of California, Davis. Infant handling was generally gentle and nonintrusive, although females sometimes tugged on infants. Females were more strongly attracted to infants than were males, regardless of their age. Adult females handled infants as often as subadult females did. Male and female infants were handled at equal rates, and rates of handling towards all infants declined sharply as infants matured. Infants were handled by related females at higher rates than by unrelated females, and at higher rates by higher-ranking females than by lower-ranking females. The data provide little support for the ‘learning to mother’ hypothesis, because older females were as interested in infants as were subadult females. Although mothers were reluctant to allow their infants to be handled, the data do not support the reproductive competition hypothesis because patterns of infant handling did not match patterns of harassment of infants. The data provide a better fit to the by-product hypothesis. Females were most strongly attracted to infants when maternal care was most critical for infant survival and females of all ages were strongly attracted to infants. Taken together, these data suggest that a strong attraction to infants is favoured by selection because females that are highly responsive to infants make good mothers.

Histologic localization of indocyanine green dye in aging primate and human ocular tissues with clinical angiographic correlation

Objective This study aimed to histologically localize indocyanine green (ICG) dye in the geriatric primate and human eye and to correlate these findings with clinical ICG angiography. Design The study design was a clinicopathologic correlation. Participants Six eyes of three geriatric monkeys ( Maccaca mulatta) with macular drusen, 19 to 29 years of age, housed at the California Primate Research Center and an enucleated human eye from a 66-year-old patient with choroidal melanoma were examined. Intervention All six monkey eyes and the human eye underwent clinical ICG angiography. Five monkey eyes were enucleated at varying intervals after intravenous ICG dye injection for histologic examination. One monkey eye was removed without prior ICG injection as an age-matched control. The human eye was enucleated after intravenous injection of ICG dye. Main outcome measures Infrared fluorescence microscopy of freeze-dried tissue sections was performed to detect ICG fluorescence. Histologic sections were stimulated with an 810-nm diode laser, and the fluorescence emitted was detected with a Hamamatsu infrared camera. The images were digitally recorded. The distribution of fluorescence on histologic examination was correlated with the fluorescence of the clinical ICG angiogram. Results Infrared fluorescence microscopy of monkey sections localized fluorescence within retinal and choroidal vessels early after injection of ICG dye. The ICG fluorescence was seen in the extravascular choroidal stroma within 10 minutes after injection. The stromal fluorescence persisted in sections obtained 50 minutes after injection of ICG. The retinal pigment epithelium (RPE)-Bruch’s membrane complex was brightly fluorescent in the middle- and latestage histologic sections. Drusen deposits were brightly fluorescent at all timepoints examined. Similar findings were observed in freeze-dried tissue sections of the human eye. The fluorescence detected on histologic sections correlated closely with the fluorescence of the clinical ICG angiograms for the same interval. Conclusions The ICG dye does not remain solely within the choroidal intravascular space but extravasates into the choroidal stroma and accumulates within the RPE. Extravascular ICG binds to drusen material. These findings will enhance the interpretation of clinical ICG angiography.

The Patterning of Intervention among Male Bonnet Macaques: Reciprocity, Revenge, and Loyalty

The Patterning of Intervention among Male Bonnet Macaques: Reciprocity, Revenge, and Loyalty

Calcium and zinc retention from protein hydrolysate formulas in suckling rhesus monkeys.

To determine calcium and zinc retention from infant formulas based on protein hydrolysates. Randomized, crossover. Newborn nursery at the California Primate Research Center, Davis. Suckling infant rhesus monkeys (N = 7), aged 6 weeks at the beginning of the study. Each infant received seven different formulas. Fasted infant monkeys were fed diets radiolabeled with calcium 47 and zinc 65. Retention was determined by counting whole body radioactivity immediately after dosing and 7 days after dosing. Retention of 47Ca was a mean (+/- SEM) of 79% +/- 4% from casein hydrolysate and 72% +/- 6% from the whey protein hydrolysate formula. Calcium 47 retention from hydrolysates based on whey protein/casein mixtures (a ratio of 60:40 or 50:50) was similar despite differences in protein sources and calcium content. Calcium 47 retention from two types of soy/collagen hydrolysate formula was found to be 68% +/- 6% and 59% +/- 4%, respectively, which is significantly lower than retention from casein hydrolysate. Considering the different calcium content of these formulas, total calcium retention from milk protein hydrolysates was higher than from soy/collagen products. Retention of 65Zn from milk protein hydrolysates ranged from 18% +/- 3% to 29% +/- 4% and was higher than that from soy/collagen formulas with a mean retention of 7% +/- 3% and 10% +/- 4%, respectively. Despite these differences in 65Zn retention, total zinc retention from all soy/collagen formulas was similar due to their higher zinc content. Calcium and zinc bioavailability was high from formulas based on milk protein hydrolysate, but was considerably lower from soy hydrolysates. Higher levels of calcium and zinc provided in soy hydrolysate formula compensated for the lower bioavailability and resulted in similar amounts of calcium and zinc retained.

Psychosocial factors and disease progression in simian AIDS

Infection of macaques by the simian immunodeficiency virus (SIV), like HIV infection in humans, results in a variable time course to clinical disease. Developmental studies of macaques have shown that psychosocial disruption, including social separations, can result in both immediate and long-term immunological consequences. Using colony records on a subset of rhesus macaques (Macaca mulatta) inoculated with SIV at the California Primate Research Center, Davis, California, USA, we constructed regression equations to determine whether the animals' psychosocial histories could explain any of the variability observed in measures of disease progression. After controlling for dosage, age at inoculation, sex, and previous inoculation history, psychosocial variables were found to be significantly associated with several indicators of disease, including latencies to display leukopenia and lymphopenia, weight loss, and survival. We believe these preliminary results suggest an important role for psychosocial processes in affecting disease progression in SIV infection in macaques.

Electron microscopy of simian immunodeficiency virus isolated from a sooty mangabey (Cercocebus Atys) in Liberia, West Africa

Simian immunodeficiency virus (SIV) is a Lentivirus that exhibits both morphological and genomic similarities to HIV. SIV has been isolated from sooty mangabeys in several primate colonies, and has been shown to be about 80% related to HTV-2. Since HIV-2 and sooty mangabeys are both indigenous to West Africa, isolation of a virus from sooty mangabeys in West Africa would be of great interest in determining the origins of these two viruses. We report here thin section transmission electron microscopy of a lentivirus from a pet sooty mangabey living in Liberia, West Africa.Peripheral blood mononuclear cells (PEMC) from a healthy pet sooty mangabey in Liberia were frozen in liquid nitrogen and shipped to the California Primate Research Center. The cells were thawed and stimulated for 72h with 0.5μg/ml Staphylococcal enterotoxin A in RPMI 1640 containing 10% fetal calf serum. 2×106PEMC were then co-cultivated with 2×106CEMxl74 cells and processed for EM.CEMxl74 cells co-cultivated with infected PBMC exhibited syncytial giant cells with patchy foamy cytoplasm (Fig 1). large numbers of virus particles were observed within these vacuoles (Fig 2).

Asymptomatic Infection of the Central Nervous System by the Macaque Immunosuppressive Type D Retrovirus, SRV-1

The aetiological agent of spontaneously occurring simian acquired immune deficiency syndrome (SAIDS) in rhesus monkeys (Macaca mulatta) at the California Primate Research Center is a type D retrovirus designated SAIDS retrovirus serotype 1 (SRV-1). SRV-1 DNA and RNA have previously been detected in the brains of rhesus monkeys with SAIDS in the absence of viral antigen or neuropathological lesions. In this study we further define the relationship between SRV-1 and the central nervous system (CNS) in rhesus monkeys by examining the CNS for infectious SRV-1, viral antigen and anti-SRV-1 antibodies. In addition, cerebrospinal fluid (CSF) was assayed for alterations in IgG and albumin levels, IgG/albumin ratios and cell count in comparison to uninfected control animals. No differences in CSF parameters were detected between infected and uninfected animals except for the presence of infectious SRV-1 which was isolated from the CSF from 13 out of 19 (68%) viraemic rhesus monkeys. The probable source of this virus was the choroid plexus, where approximately 1 in 1000 surface epithelial cells were found to contain viral antigen by immunohistochemistry. Antibodies against SRV-1 were not detected in the CSF even when present in the serum. Neither infectious virus nor viral antigen were found in the brain parenchyma of any animal examined. Thus infection of the CNS by SRV-1 appears to be subclinical without an intrathecal immune response. This may be related to the apparent restriction of productive infection in the CNS to cells of the choroid plexus.

Infant cross-fostering between Japanese (Macaca fuscata) and rhesus macaques (M. mulatta).

Cross-fostering of infant rhesus macaques between unrelated females has become a routine management strategy at the California Primate Research Center. In order to study the effect of environmental factors on vocal development, we extended this procedure to offspring exchange between two different macaque species living in small social groups. A total of four neonatal Japanese and rhesus monkeys were fostered onto mothers of the other species. Six attempts were required, for an overall success rate of 67%. However, two of the adoptions involved the same foster mother, and both rejections occurred with the same female. The cross-fostered individuals gained weight normally in the first year of life and did not require any hospital treatment. These results indicate that raising nonhuman primate infants with members of a different species can be a viable means of altering species-typical experience without sacrificing essential aspects of maternal care, socialization, and psychological well-being.

Reproductive synchrony in captive macaques.

Captive bonnet macaques housed at the California Primate Research Center reproduce seasonally. The chances of producing surviving infants were substantially reduced among females who conceived at the peak of the mating season compared with females whose conceptions were more isolated in time. Primiparous females and low ranking females were most consistently affected by the extent of reproductive synchrony. Behavioral data suggest that harassment of conceiving and pregnant females may have contributed to the correlation between the extent of reproductive synchrony and infant mortality as the levels of aggression toward females were highest during the months in which conceptions were most common.

Distribution of a macaque immunosuppressive type D retrovirus in neural, lymphoid, and salivary tissues.

Simian acquired immune deficiency syndrome (SAIDS) in rhesus macaques (Macaca mulatta) at the California Primate Research Center is caused by a type D retrovirus designated SAIDS retrovirus serotype 1 (SRV-1). This syndrome is characterized by profound immunosuppression and death associated with opportunistic infections. Neurologic signs and lesions have not been described as part of this syndrome. The distribution of SRV-1 in the salivary glands, lymph nodes, spleens, thymuses, and brains of eight virus-infected rhesus macaques was examined by immunohistochemistry. Electron microscopy, in situ RNA hybridization, and Southern blot hybridization were also performed on selected tissues to detect viral particles, RNA, and DNA, respectively. In seven of eight SRV-1-infected animals, the transmembrane envelope glycoprotein (gp20) of SRV-1 was present in three or more tissues, but never in the brain. In the remaining animal, no viral antigen was detected in any tissue. In this same group of animals, viral nucleic acid was detected in the lymph nodes of six of six animals by Southern blot hybridization, in the salivary glands of two of five animals by both Southern blot and in situ hybridizations, and, surprisingly, in the brains of three of three animals by Southern blot and of three of five animals by in situ hybridization, including the one animal in which viral gp20 was undetectable. None of these animals had neurologic signs or lesions. The detection of viral nucleic acid in the absence of viral antigen in the brain suggests latent SRV-1 infection of the central nervous system.

Oral lesions in rhesus monkeys associated with infection by simian AIDS retrovirus, serotype-I (SRV-1)

Simian acquired immunodeficiency syndrome (SAIDS) is a retrovirus-induced immunodeficiency disease that affects certain nonhuman primates and has many parallels to human AIDS. We examined 72 rhesus monkeys ( Macaca mulatta) exposed to SAIDS retrovirus serotype-1 (SRV-1) and 81 healthy control monkeys at the California Primate Research Center to determine the prevalence of oral lesions. At the time of examination, 69 of the 72 monkeys exposed to SRV-1 had serologic and/or virologic evidence of SRV-1 infection. None of the 81 control monkeys had any evidence of infection with SRV-1. Acute necrotizing ulcerative gingivitis (ANUG), oral yeast infections, and noma occurred in 10% ( p < 0.01), 4%, and 1%, respectively, of the study group of 72 animals but were found in none of the control animals. Thus, ANUG occurs rather frequently in rhesus monkeys with evidence of SRV-1 infection. The reproducible immunodeficiency that follows inoculation of SRV-1 in rhesus monkeys promises to be a useful model for studying the pathogenesis of ANUG associated with immunodeficiency.

Natural History of Endemic Type D Retrovirus Infection and Acquired Immune Deficiency Syndrome in Group-Housed Rhesus Monkeys&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;

A 2.5-year epidemiologic study of a breeding group of rhesus monkeys (Macaca mulatta), which is a focus of endemic simian acquired immunodeficiency syndrome (SAIDS), demonstrated a strong association between the occurrence of SAIDS and infection with a type D retrovirus, SAIDS retrovirus serotype 1 (SRV-1). Of 23 healthy "tracer" juvenile rhesus monkeys, 19 (83%) died with SAIDS within 9 months of introduction into the resident SAIDS-endemic population. In contrast, 21 healthy "sentinel" juvenile rhesus monkeys placed in the same outdoor enclosure but denied physical contact with the SAIDS-affected group by a 10-foot-wide "buffer zone" remained free of SRV-1, SRV-1 antibody, and disease for 2.5 years. The SAIDS-specific mortality rate was significantly higher in juveniles than in adults. In repeated serologic testing, the overall prevalence of SRV-1 antibody ranged from 68 to 85%. Antibody prevalence increased with age. Seroconversion was found to be a poor indicator of infection rate, as approximately 50% of virus-positive juvenile monkeys had no antibody detectable by enzyme-linked immunosorbent assay. Repeated viral isolations from all animals revealed 1) SRV-1 viremia with clinical SAIDS; 2) persistent viremia and viral shedding in apparently healthy animals; 3) transient viremia and clinical recovery; 4) intermittent viremia, suggesting activation of latent infections; and 5) viremia in a 1-day-old infant, suggesting transplacental transmission. The prevalence of SRV-1 antibody in SAIDS-free breeding groups of rhesus monkeys was 4%. The seroprevalence of antibodies against human T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus (HIV), and simian immunodeficiency virus (SIV; formerly STLV-III) was uniformly low or absent in both SAIDS-free and SAIDS-affected groups of rhesus monkeys, demonstrating that these retroviruses are not etiologically linked to SAIDS at the California Primate Research Center.

Infant cross‐fostering in rhesus monkeys (Macaca mulatta): A procedure for the long‐term management of captive populations

Because of the constraints of captivity, captive populations are generally closed to the introduction of unrelated individuals and may eventually experience inbreeding depression and its associated problems. As a means of increasing genetic diversity in established social gropus of rhesus monkeys at the California Primate Research Center, 36 infants were used as subjects in a cross-fostering experiment in which 27 infants (75%) were successfully integrated into non-natal groups by fostering them onto unrelated females. These results have important practical implications for maintaining self-sustaining populations of captive rhesus monkeys and may eventually be extended to other captive species. Cross-fostering infants between captive social populations may be an important means of minimizing the higher mortality and morbidity and reduced fertility effects associated with inbreeding depression. Furthermore, this procedure causes a minimum of social disruption and reduces the chances that older animals introduced into new groups will be traumatized.

Immune defects in simian acquired immunodeficiency syndrome

We recently reported a Simian Acquired Immunodeficiency Syndrome (SAIDS) in rhesus macaques at the California Primate Research Center. Here, we studied in vitro lymphocyte response to the mitogens Concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) with and without interleukin 2 (IL-2). Immunoglobulin (IgG and IgM) and complement (C3 and C4) concentrations were determined by radial immunodiffusion. T helper and T suppressor lymphocytes were identified with the monoclonal antibodies OKT4 and OKT8. Concentrations of IgG and IgM were significantly (p <.05) decreased. Complement component C3 did not change but C4 was increased. The absolute lymphocyte count decreased but the OKT4:OKT8 ratio was unchanged from controls. A decreased lymphocyte response to all mitogens occurred early and became more severely depressed near death. IL-2 caused a complete or partial restoration of the response to the mitogens CON A and PHA. Both the humoral and cell mediated immune responses are affected in SAIDS. The role of IL-2 in this immune defect must be studied further.

Factors associated with birth rate and live birth rate in multi-male breeding groups of rhesus monkeys.

Reproductive records of 284 female rhesus monkeys housed in six multimale corrals at the California Primate Research Center were examined for the birth seasons 1977-1982 to determine possible associations between the probability of birth or live birth and female age, parity, origin, parturition in the previous season, infant birth date, and infant birth date in previous season. Multiple logistic regression analysis was used to identify and quantitate the effects of factors on the probability of birth or live birth, while controlling for the possibly confounding effects of other factors in the model. Females who had infants early in the previous season were 2.5 times as likely to give birth as those who had infants late in the previous season. Females with two or three previous births were 2.1 times as likely to give birth, and those with four or five previous births were 6.7 times as likely to give birth as were females with no or one previous birth. Controlling for other factors (age, parity, and timing of birth in the previous season), corralborn females were 3.3 times as likely to give birth as either wild-caught or domestic-born monkeys not native to the corrals. Domestic-born females who were not corral natives were 0.3 times as likely to have live births as wild-caught females. Births late in the season were 1.8 times as likely to result in live infants as births early in the season.

Triadic interactions among Macaca radiata: Passports and buffers.

Male members of a group of captive Macaca radiata at the California Primate Research Center held and carried infants as they approached or were approached by higher-ranking males and as they were threatened by other males. Male infants between the ages of 25 and 84 weeks were involved in triadic interactions more frequently than were female infants of any age or male infants of other ages. That males were less likely to be harassed while huddling with or embracing infants suggested that infants provided an effective buffer against aggression.

Do these primates have AIDS?

Both a condition resembling acquired immunodeficiency syndrome (AIDS) in humans and an unusual number of certain malignant neoplasms have occurred spontaneously in two primate colonies on opposite coasts of the United States. While the relationship between what some are calling simian AIDS and the human disease is unknown, it's possible that a primate model for human AIDS soon may be available. The outbreaks occurred in several macaque monkey species at both the New England Primate Research Center in Southborough, Mass, and the California Primate Research Center at the University of California, Davis. The primary species affected were cyclopis monkeys (<i>Macaca cyclopis</i>) at the New England center and rhesus monkeys (<i>Macaca mulatta</i>) at the California center. Most of the monkeys were being raised for future research purposes. The investigators discounted any effects of treatments on those currently being used in research protocols. "In recent years it became apparent that there were

Do these primates have AIDS?

Both a condition resembling acquired immunodeficiency syndrome (AIDS) in humans and an unusual number of certain malignant neoplasms have occurred spontaneously in two primate colonies on opposite coasts of the United States. While the relationship between what some are calling simian AIDS and the human disease is unknown, it's possible that a primate model for human AIDS soon may be available. The outbreaks occurred in several macaque monkey species at both the New England Primate Research Center in Southborough, Mass, and the California Primate Research Center at the University of California, Davis. The primary species affected were cyclopis monkeys (Macaca cyclopis) at the New England center and rhesus monkeys (Macaca mulatta) at the California center. Most of the monkeys were being raised for future research purposes. The investigators discounted any effects of treatments on those currently being used in research protocols. In recent years it became apparent that there were

EPIDEMIC OF ACQUIRED IMMUNODEFICIENCY IN RHESUS MONKEYS

A syndrome closely resembling acquired immunodeficiency syndrome (AIDS) in man has been identified in a group of 64 rhesus monkeys ( Macaca mulatta) maintained outdoors at the California Primate Research Center. The syndrome is characterised by generalised lymphadenopathy, severe opportunistic infections including cytomegalovirus, chronic wasting, and high mortality. In 1 animal a multifocal cutaneous fibrosarcoma developed. This syndrome in monkeys may provide an animal model for human AIDS.

Brief report: Chromosomal analysis of perinatal death in Macaca mulatta and Macaca radiata.

Peripheral blood samples from 53 macaque perinatal deaths at the California Primate Research Center (CPRC) were cultured to produce chromosomes for analysis. Karyotypes were constructed for 26 successful cultures and revealed no apparent chromosomal anomalies. A genetic screening program at primate breeding facilities is important for estimating the frequency of chromosomal anomalies in macaques and for understanding the contribution of chromosomal anomalies to reproductive loss and congenital malformations in macaques.