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PubMed1990

Immunological studies of the basis for the apathogenicity of simian immunodeficiency virus from African green monkeys.

Potential reasons for the lack of pathogenicity of the simian immunodeficiency virus SIVagm in its natural host, the African green monkey (AGM, Cercopithecus aethiops), were investigated with respect to immunological mechanisms. The functional immune response of monkeys to infection was similar (though not identical) to that of humans to infection with human immunodeficiency virus type 1 (HIV-1). In the sera of infected animals, neutralizing antibodies were found to be low or absent, and in particular there was no neutralization of the various isolates by homologous sera. There was no detectable antibody/complement cytotoxicity, though AGM sera were able to initiate antibody-dependent cellular cytolysis of infected cells in the presence of healthy effector peripheral blood lymphocytes. As in the human/HIV system, macrophages from AGMs are readily infected by SIVagm. Two possibly important differences between the AGM/SIVagm system and the human/HIV system are (i) the low immune response of the AGMs to the core protein of SIVagm and (ii) the significantly lower inhibitory effect of SIVagm proteins on the proliferation of AGM lymphocytes.

Animals↗
PubMed1991

Resolution of the African hominoid trichotomy by use of a mitochondrial gene sequence.

Mitochondrial DNA sequences encoding the cytochrome oxidase subunit II gene have been determined for five primate species, siamang (Hylobates syndactylus), lowland gorilla (Gorilla gorilla), pygmy chimpanzee (Pan paniscus), crab-eating macaque (Macaca fascicularis), and green monkey (Cercopithecus aethiops), and compared with published sequences of other primate and nonprimate species. Comparisons of cytochrome oxidase subunit II gene sequences provide clear-cut evidence from the mitochondrial genome for the separation of the African ape trichotomy into two evolutionary lineages, one leading to gorillas and the other to humans and chimpanzees. Several different tree-building methods support this same phylogenetic tree topology. The comparisons also yield trees in which a substantial length separates the divergence point of gorillas from that of humans and chimpanzees, suggesting that the lineage most immediately ancestral to humans and chimpanzees may have been in existence for a relatively long time.

Animals↗
PubMed1995

The U3 promoter region of the acutely lethal simian immunodeficiency virus clone smmPBj1.9 confers related biological activity on the apathogenic clone agm3mc.

Infection with the acutely pathogenic molecular virus clone SIVsmmPBj1.9, cloned from isolate PBj14 of simian immunodeficiency virus (SIV) from sooty mangabey monkeys (Cercocebus atys), leads to acute viral and often lethal disease within days or weeks. SIVsmmPBj1.9 has the unique property of replicating in nonstimulated peripheral blood mononuclear cells from pig-tailed macaques. In contrast, molecular virus clone SIVagm3mc of SIV from African green monkeys (Cercopithecus aethiops), which is apathogenic in its natural host and in pig-tailed macaques, is unable to grow in nonstimulated peripheral blood cells. Chimeric proviruses were constructed by exchanging defined regions of SIVagm3mc against comparable regions of SIVsmmPBj1.9. Four of five hybrid viruses generated by transfection into the CD4-positive T-cell line C8166 replicated in T-cell lines permissive for SIVagm3mc replication and in stimulated peripheral blood cells from pig-tailed macaques and from African green monkeys. Three hybrid viruses displayed the distinct biological property of SIVsmmPBj14 to replicate in nonstimulated peripheral blood cells from pig-tailed macaques and from African green monkeys. Replication in nonstimulated peripheral blood cells was dependent on the presence of the U3 promoter region of SIVsmmPBj1.9 within the viral long terminal repeat.

Animals↗
PubMed1997

Vaccine effect using a live attenuated nef-deficient simian immunodeficiency virus of African green monkeys in the absence of detectable vaccine virus replication in vivo.

Immunization of adult macaques with live attenuated simian immunodeficiency viruses (SIVs) lacking the nef genes has been shown to protect against challenge with full-length pathogenic SIV. To test live attenuated virus vaccines for the first time in a natural host we have constructed a mutant SIV from African green monkeys (SIVagm) with a deletion of 125 bp in the nef gene (SIVagm3 delta nef). This mutant showed moderately delayed in vitro replication in the T cell line MOLT-4/8 and in primary peripheral blood mononuclear cells from African green monkeys (Cercopithecus aetiops) and pig-tailed macaques (Macaca nemestrina) compared with cloned wild-type SIVagm3. In contrast, in vivo replication of SIVagm3 delta nef in African green monkeys was severely impaired or undetectable and did not induce seroconversion. After challenge with wild-type SIVagm3 the SIVagm3 delta nef preinoculated African green monkeys showed a memory antibody response that declined after week 2. In three of four African green monkeys the cell-associated virus load and in two of four African green monkeys the plasma virus load was dramatically decreased after the challenge compared with naive control animals. The remaining animal showed no evidence of productive challenge virus replication. This study demonstrates that a strong vaccine effect or protection in the SIVagm/African green monkey system is possible using a live attenuated vaccine in the absence of a productive infection and corresponding humoral immune response.

Animals↗
PubMedDate not supplied

Effect of dietary plant and animal protein intake on sperm quality in monkeys.

This study was conducted to evaluate the influence of animal and plant protein diets on sperm quality indices over 120 days, using the vervet monkey (Cercopithecus aethiops), as a model. These experiments were divided into a 60-day period of high-protein consumption (+/-17% crude protein), followed by a 60-day term of sustainable protein intake (+/-9% crude protein). All the diets were designed to be similar, except for the source of dietary protein that the animals consumed. High-protein diets containing milk solids or maize + legumes had no significant effect on sperm quality parameters over the first 60 days. During the next 60 days of the investigation, sustainable plant and animal protein diets had differential effects on a number of sperm quality indices. When compared to the plant-based diet, the monkeys that were given the animal protein diet containing milk solids had lower sperm counts (p < .04), reduced sperm motility (p = .04), higher sperm midpiece abnormalities (p < .05), and a trend (p = .10) towards increased sperm head defects. These findings shed some light on the impact of variable dietary proteins on sperm quality, but should be followed by longer-term investigations around this important reproductive health issue.

Animals↗
PubMed1963

An electron microscope study of the development of SV40 virus.

Kidney cells, predominantly from Cercopithecus monkeys but also from baboons, were infected in vitro with the SV40 virus. The infectious cycle was studied with the electron microscope by means of thin sections of cells fixed from 3 hours up to 11 days after infection. The frequency of virus formation and various nuclear and cytoplasmic lesions in relation to the infection are described. The virus particles appear in the nucleus in close contact with the chromatin. In a small number of cells they have been observed as early as 10 to 12 hours after infection, but most often they appear 24 to 48 hours afterward. Their mean diameter is 33 mmicro. They have no membrane and are frequently arranged as crystal-like structures. In addition to the appearance of virus, one observes various lesions in the nucleoplasm and particularly in the nucleolus, which shows an early hypertrophy and produces unusual, dense condensations in contact with the nucleolonema. The importance of these nucleolar lesions and the relationship between the SV40 virus and the polyoma, common wart, and Shope papilloma viruses are discussed.

Cell Nucleolus↗
PubMed1964

INCOMPLETE SIMIAN PAPOVAVIRUS SV40. FORMATION OF NON-INFECTIOUS VIRAL ANTIGEN IN THE PRESENCE OF FLUOROURACIL.

A study was made of the effects of 5-fluorouracil (FU) and 5-fluorodeoxyuridine (FUDR) on the replication of the simian papovavirus SV40 in cercopithecus monkey kidney cells and on the production of virus antigen by these cells. Both drugs markedly suppressed the production of new infectious virus by SV40-infected cells. Synthesis of viral protein was also markedly suppressed by FUDR, but not by FU. In the presence of FU, infected cells produced large amounts of viral protein which were detected by the fluorescent antibody technique. The antigen was not distributed in a particulate fashion as in untreated cells. Diffuse virus antigen was observed in the nuclei of FU-treated cells, resembling the distribution of antigen near the end of the eclipse period in untreated, infected cultures. This stage of antigen production presumably preceded viral assembly. Virus particles with or without cores were rarely seen with the electron microscope in infected FU-treated cells, although large numbers of SV40 particles were readily visualized in untreated, infected cells. It appears that at least one antigenic protein of this papovavirus is synthesized abundantly in FU-treated cells, but is not assembled into virus shells in the presence of the inhibitor.

Animals↗
PubMed1999

Adenovirus-mediated transgene expression in nonhuman primate brain.

Transgene expression in the brain of St. Kitts green monkey, Cercopithecus aethiops sabeus, was studied following injection of a serotype 5 adenoviral vector deleted in E1 and E3. The vector harbored the transgene for Escherichia coli beta-galactosidase (beta-Gal) with the simian virus 40 (SV40) nuclear localization signal under control of the Rous sarcoma viral (RSV) long terminal repeat. Several titers ranging from 5 x 10(7) to 2 x 10(9) plaque-forming units (PFU) in volumes ranging from 5 to 250 microl were injected into the caudate nuclei of 18 monkeys. Monkeys were treated with dexamethasone for 9 days, beginning the day prior to surgery, and were sacrificed at 1 week or at 1, 2, or 3 months. At 1 week, beta-Gal was expressed in thousands of cells, including both neurons and astrocytes. In addition, some dopaminergic neurons in the substantia nigra expressed transgene, suggesting retrograde transport of the vector. At 1 month 162,000+/-68,000 (SEM) or 65,000+/-29,000 beta-Gal-expressing cells persisted in striatum injected with 6 x 10(8) PFU in 30 microl or 5 x 10(7) PFU in 5 microl, respectively. Transgene expression was also observed in one of two monkeys sacrificed at 2 months and in a single monkey sacrificed at 3 months. No transgene expression was observed at 1 month in striatum injected with a higher titer (2 x 10(9) PFU in 100 microl) or more dilute vector (5 x 10(7) PFU in 30 microl). Staining for the major histocompatibility complex II (MHC II) subtype DR showed intense staining in sites injected with a higher vector titer, in which no transgene persisted at 1 month, whereas low to moderate staining was present in sites with high transgene expression. These observations suggest that there is an optimal range of vector titers for obtaining persistent transgene expression from E1E3-deleted adenovirus in primate brain, above which host responses limit transgene stability.

Adenoviridae↗
PubMed1998

Simian T cell leukemia virus type I-induced malignant adult T cell leukemia-like disease in a naturally infected African green monkey: implication of CD8+ T cell leukemia.

Spontaneous T cell leukemia was found in an African green monkey (Cercopithecus aethiops, AGM) naturally infected with simian T cell leukemia virus type I (STLV-I). The hematological features and the evidence for monoclonal integration of provirus DNA in the leukemic cells revealed that the leukemia was an ATL-like disease. The expression of surface markers on the leukemic cells indicated that they were defined as an activated CD8+ T cell subset. Together with the finding that seven in vitro spontaneously STLV-I-transformed cell lines were CD4-CD8+, it is likely that CD8+ T cells are transformed by STLV-I in AGMs, in contrast with human ATL. Finally, we assessed characteristics of the CD8 chains on these transformed cells. The result indicated that the leukemic cells expressed only the alpha chains but not the beta chains. However, in the case of in vitro-transformed cell lines the expression pattern of the CD8 chains varied in individual monkeys. Thus, STLV-I may preferentially transform CD8+ (both alphaalpha+ and alphabeta+) T cells in AGMs.

Adult↗
PubMed1977

Polymorphonuclear neutrophilic leukocytes in protein deficiency.

The number of white blood cells and of polymorphonuclear leukocytes remained unchanged in vervet monkeys (Cercopithecus aethiops) receiving a "O" protein diet. The motility of the polymorphonuclear leukocytes and their phagocytic and killing indices with and without leukokinin stimulation decreased in protein-depleted animals. Acid cathepsin decreased, DNA relatively increased, and peroxidase, alkaline phosphatase, acid phenylphosphatase, and lysozyme reached higher levels in the polymorphonuclear leukocytes of animals on a "O" protein diet.

Animals↗
PubMed1979

The effect of oral pancreatic enzymes on the intestinal flora of protein-deficient vervet monkeys challenged with Vibrio cholerae.

Jejunal bacterial flora in 11 protein deficient vervet monkeys (Cercopithecus aethiops) and four controls was studied. These were the same animals from an investigation previously reported in which it was shown that pancreatic extract modified the course of cholera infection in protein-deficient monkeys. The present study reports in addition that these animals the fluid in the upper jejunum contained significantly increased numbers of bacteria including Enterobacteriaceae compared to its predietary state and to that of the controls. After challenge to these animals with Vibrio cholerae, the jejunal bacterial flora in the protein-deficient animals given placebo remained unchanged, whereas pancreatic extract-treated animals showed a quantitative and qualitative recovery of their jejunal bacterial flora. Pancreatic extract hastened the return of altered intestinal flora to predietary levels.

Animals↗
PubMed1992

Psyllium husk. I: Effect on plasma lipoproteins, cholesterol metabolism, and atherosclerosis in African green monkeys.

Psyllium's effects on plasma and lipoprotein cholesterol concentrations, cholesterol metabolism, and diet-induced atherosclerosis were studied in adult male African green monkeys (Cercopithecus aethiops). Animals were fed for 3.5 y one of three experimental diets: low-cholesterol cellulose (LCC), high-cholesterol cellulose (HCC), or high-cholesterol psyllium (HCP). The LCC and HCP groups had significantly (P less than 0.05) lower plasma cholesterol concentrations (39% lower) at 1 mo than did the HCC group. These responses persisted throughout the study. Plasma cholesterol changes were due to a reduction in intermediate-density and low-density lipoproteins; very-low and high-density-lipoprotein concentrations were similar among groups. Aortic atherosclerosis, evaluated as percent sudanophilia at 3.5 y, was lowest in the LCC group, intermediate in the HCP group, and highest in the HCC group. Cholesterol absorption, neutral steroid and fat excretion, HMGCoA reductase activity (in intestine and liver), and body weight were unrelated to psyllium's hypocholesterolemic effects.

Animals↗
PubMed1989

Effect of prolonged infusion of ANF in normotensive and hypertensive monkeys.

It is now recognized that bolus and short-term infusions of atrial natriuretic factor (ANF) into different species lead to a slight and transient decrease of blood pressure, while prolonged infusions cause a significant blood pressure reduction in hypertensive but not in normotensive rats. The present study was designed to evaluate the effects of prolonged ANF infusions on blood pressure and humoral parameters in normotensive and hypertensive African green monkeys (Cercopithecus aethiops). Human-ANF infusions (100 ng/kg.hr) in conscious, normotensive vervets for a period of 48 hours evoked highly significant decreases of blood pressure (from 124/65 to 104/53 mm Hg), plasma renin activity, aldosterone, and hematocrit. This fall in blood pressure was not accompanied by an increase of plasma cGMP levels at the end of the infusion. Forty-eight hours after the infusion was terminated, the decrease in blood pressure was still significant (97/46 mm Hg), as was the drop in aldosterone. In hypertensive monkeys, systolic blood pressure declined from 175 +/- 8 to 130 +/- 8 mm Hg, while diastolic pressure fell from 117 +/- 10 to 88 +/- 4 mm Hg. These data demonstrate that the chronic infusion of ANF in both normotensive and hypertensive vervets has more profound effects than does acute bolus administration, effects that persist for a prolonged period of time after discontinuation of the infusion.

Animals↗
PubMed1990

Cognitive and motor deficits in the acquisition of an object retrieval/detour task in MPTP-treated monkeys.

To assess functional changes following treatment with 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) in monkeys, we studied a task that reveals sensitivity to dopamine deficits under various conditions. The task required retrieval of a banana slice from a transparent box that is open on one side and fastened to a tray. Successful performance required the subject to suppress a tendency to reach directly at the reward while (1) orientation of the open side, (2) position on the tray, and (3) position of the banana in the box were manipulated in order to vary the cognitive and motor difficulty of the trial. African green monkeys (Cercopithecus aethiops sabaeus) were treated with MPTP (1.5-1.6 mg/kg cumulative dose over 4-5 days). A control group was sham treated (n = 12). MPTP-treated subjects either became severely symptomatic, showing motor impairments that prevented them from performing, or showed no gross motor impairment (n = 6) in spite of major depletions in dopamine concentrations. MPTP-treated subjects showed impaired acquisition of the task when tested 8-12 months later. They made more errors during the sessions, specifically on the trials that were related to cognitive complexity, such as attempting to reach directly towards the reward through the transparent side of the box (a barrier reach), instead of reaching around it (detour) into the open side, as well as other awkward, perseverative or delayed reaches. MPTP appears to cause both cognitive and motor deficits in the acquisition of this task 8-12 months after treatment, even in the group of monkeys which never showed gross motor deficits.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMedDate not supplied

Mycobacterium simiae and related mycobacteria.

Fifty mycobacterial strains were isolated from freshly imported tuberculin-negative Macacus rhesus and Cercopithecus ethiops monkeys. Of these strains, 14 were identified as Mycobacterium simiae and 4, as Mycobacterium asiaticum. These two species are slow growing with a delayed photochromogenicity. M. Simiae is niacin-positive. Both species are resistant to the antituberculous chemotherapeutic compounds streptomycin, isoniazid, p-aminosalicylate, and rifampin but are sensitive to cycloserine. The two species are virulent for white mice. Infection is contagious; 25% of noninfected cage mates become infected during 12--60 days of exposure to infected animals. Intrauterine transmission of infection also occurs. Utilizing the gel-precipitation method, we have observed up to 16 antigens in each species. Four to six antigens are shared with Mycobacterium tuberculosis. Mycobacterium species strain 52 is antigenically distinct. The 14 strains of M. simiae belong to two serotypes. Mycobacterium habana belongs to M. simiae serotype 1.

Animals↗
PubMed1983

In vivo antiviral activity of recombinant type alpha interferon A in monkeys with infections due to simian varicella virus.

Recombinant type alpha interferon A (rIFN-alpha-A) administered to African green monkeys (Cercopithecus aethiops) intramuscularly in a dose of 3 X 10(6) units/kg of body weight resulted in substantial blood levels of interferon. Peak levels of greater than 1,000 units/ml of serum appeared at 1 and 2 hr after inoculation and interferon was detectable for as long as 12 hr after inoculation. Injection of rIFN-alpha-A at a dose of 10(6) units/kg twice daily for eight days effectively inhibited simian varicella virus infection of the African green monkey. Antiviral activity was demonstrated in monkeys with prophylactic treatment begun 4 hr prior to virus inoculation or with therapeutic treatment deferred until 44 hr after virus inoculation. No adverse effects of treatment were observed.

Animals↗
PubMed1992

Pathogenic potential of filoviruses: role of geographic origin of primate host and virus strain.

African filoviruses have caused outbreaks of fulminating hemorrhagic fever among humans. In 1989, related filoviruses were isolated from cynomolgus monkeys imported into the United States from the Philippines. The pathogenic potential of these new filoviruses was compared in 16 Asian monkeys (Macaca fascicularis-cynomolgus) and 16 African monkeys (Cercopithecus aethiops-African green) using African filoviruses from Zaire (Ebola virus) and Sudan or Asian filoviruses (Reston and Pennsylvania). African filovirus infections resulted in earlier death (P = .005), had a shorter duration of disease and median incubation period (3-4 vs. 7 days), and had earlier peak viremia (5-7 vs. 7-9 days). African green monkeys showed significantly higher survival than cynomolgus monkeys (P less than .01), and some were asymptomatic as have been humans accidentally infected with Asian filovirus. Rechallenge experiments showed that protection in survivors of filovirus infections against fatal challenge with Ebola (Zaire) virus is unpredictable. The minimal clinical disease observed in humans infected with the Reston strain is consistent with host- and virus-dependent pathogenicity.

Africa↗