Novel Endogenous Type C Retrovirus in Baboons: Complete Sequence, Providing Evidence for Baboon Endogenous Virus gag-pol Ancestry

A complete endogenous type C viral genome has been isolated from a baboon genomic library. The provirus, Papio cynocephalus endogenous retrovirus (PcEV), is 8,572 nucleotides long, and 38 to 59 proviral copies per baboon genome are found. The PcEV provirus possesses the typical simple retroviral gene organization, including two long terminal repeats and genes encoding gag, pol, and env proteins. The open reading frames for gag-pol and env are complete but have premature stop codons or frameshift mutations. The primer binding site of PcEV is complementary to tRNAGly. The gag and pol genes of PcEV are closely related to those of the baboon endogenous virus (BaEV). The env coding region of PcEV is related to the env genes of type C retroviruses. This suggests that PcEV is one of the ancestors of BaEV contributing the type C gag-pol genome fragment to the type C/D recombinant virus BaEV. Earlier it was shown that another endogenous type D virus (simian endogenous retrovirus) provided the env gene for BaEV (A. C. van der Kuyl et al., J. Virol. 71:3666-3676, 1997).     

Expression of baboon endogenous virus in exogenously infected baboon cells.

Strains of low-passage, fetal diploid, baboon (Papio cynocephalus) fibroblasts were susceptible to exogenous infection with three independent isolates of baboon endogenous virus, as measured by an immunofluorescence assay specific for viral p28. Infectivity of the M7 strain of baboon endogenous virus for baboon cells of fetal skin muscle origin was equivalent to that for human and dog cells in that similar, linear, single-hit titration patterns were obtained. The assay for supernatant RNA-dependent DNA polymerase, however, showed that baboon cells produced only low levels of virus after infection compared with the production by heterologous cells. The results showed that baboon endogenous virus was capable of penetrating baboon cells and that viral genes were expressed in infected cells. Replication of complete infectious virus was restricted, however, indicating that in this primate system homologous cells differentially regulated the expression of viral genes.     

The Ap-Bp blood groups of baboons

Four isoimmunized baboons each produced isoantibodies defining a number of blood factors of baboon blood of which two, A^p and B^p, have been most intensively studied. The two blood factors determine the A^P-B^P blood group system which, judging from its serological behavior, may be the baboon analogue of the human M-N system and the chimpanzee V-A-B system. Tests for A^P-B^P types of 592 baboons showed striking differences in the distributions of the four types among the four sub-species, Papio cynocephalus, Papio anubis, Papio ursinus (South Africa) and Papio papio (Senegal). The baboon A^P-B^P types could also be demonstrated by tests on the red cells of geladas (Theropithecus gelada). If one assumes inheritance by multiple allelic genes, then the existence of only a single gene O^p need be invoked for Papio ursinus, three alleles O^p, A^p and B^p for Papio cynocephalus and Papio anubis, but four alleles for Papio papio including an allele, very frequent in that subspecies, which determines an agglutinogen having both blood factors A^p and B^p.     

A naturally occurring epizootic of simian agent 8 in the baboon

An epizootic of genital lesions was observed on baboons (four Papio sub-species) housed in two different outdoor breeding corrals. Serological analysis revealed strong prevalence of antibodies to Simian Agent 8 (SA8). This herpesvirus was subsequently recovered from skin lesions and identified by restriction endonuclease digestion of infected cell DNA. Observations of lesion type, frequency and location were suggestive of venereal transmission. The remarkable similarity between infection resulting from SA8 in baboons and herpes simplex virus in man suggests that the baboon is an excellent model in which to study genital herpes virus transmission and infection.     

Etiological aspects of leukemias in primates including man

Attempts have been made to induce viral leukemia in monkeys (Papio hamadryas and Macaca arctoides) by inoculating them with blood from humans with different types of leukemias. In hamadryas baboons, the disease spread horizontally. By today 218 P. hamadryas and 5 M. arctoides monkeys had died of malignant lymphoma. The following viruses have been isolated from sick monkeys: lymphotropic baboon herpes virus (HVP), endogenous baboon C type viruses--xenotropic (BILN), and ecotropic (EVPG). C type oncovirus called "plasmic", which differs immunologically from the endogenous one, was also detected in the blood of sick animals. Altogether 165 sera from baboons, different species of macacas and chimpanzee were examined by the immunofluorescent technique for antibodies to HTLV virus isolated recently from sick humans with T cell leukemia/lymphoma. Antibodies to HTLV virus were detected only in monkeys (P. hamadryas and M. arctoides) with malignant lymphomas or in those which had been in close contact with them. Possible origin of simian HTLV-like virus is discussed. It originates either from leukemic patients or there is a family of primate HTLV like viruses related to the occurrence of leukemia.     

Systematic reconsideration and a revision of the nomenclature of Kenya baboons

Two populations of baboons in Kenya, often given different specific names, Papio doguera and Papio cynocephalus, were the subject of this investigation. We conducted a field study to determine if these two populations are the same or two different species. We located a zone of contact between the two putative species in the area of Simba Springs and Ithumba Hill. The population in this area was found to represent intergradation on the basis of field observations and detailed metric observations of the morphology. The morphology of this population appears to be intermediate between that of the two populations: the olive baboon, labeled Papio doguera, and the yellow baboon, labeled Papio cynocephalus. We confirmed the findings by statistical analyses of osteometric data. Since the specific separation of the two taxa studied in this investigation is invalid, both are placed in the prior nomen, Papio cynocephalus (Linnaeus, 1766) separating them on the subspecific level, P. c. doguera and P. c. cynocephalus.     

Class I MHC expression in the yellow baboon

MHC class I molecules play a crucial role in the immune response to pathogens and vaccines and in self/non-self recognition. Therefore, characterization of MHC class I gene expression of Papio subspecies is a prerequisite for studies of immunology and transplantation in the baboon (papio hamadryas). To elucidate MHC class I expression and variation within Papio subspecies and to further investigate the evolution of A and B loci in Old World primates, we have characterized the expressed class I repertoire of the yellow baboon (Papio hamadryas cynocephalus) by cDNA library screening. A total of nine distinct MHC class I cDNAs were isolated from a spleen cDNA library. The four A alleles and four B alleles obtained represent four distinct loci indicating that a duplication of the A and B loci has taken place in the lineage leading to these Old World primates. No HLA--C homologue/orthologue was found. In addition a single, nonclassical homologue of HLA--E was characterized. Examination of nucleotide and extrapolated protein sequences indicates that alleles at the two B loci are much more diversified than the alleles at the A loci. One of the A loci in particular appears to display very limited polymorphism in both Papio hamadryas cynocephalus and Papio hamadryas anubis subspecies. The failure to detect a homologue of HLA--C in the baboon provides additional evidence for the more recent origin of this locus in the pongidae and hominidae: Further comparative analysis with MHC sequences among the primate species reveals specific patterns of divergence and conservation within class I molecules of the yellow baboon.     

Baboon endogenous virus genome. I. Restriction enzyme map of the unintegrated DNA genome of a primate retrovirus

A detailed restriction map was deduced for the genome of an endogenous retrovirus of a higher primate, that of baboon. The cleavage sites for 12 restriction enzymes were mapped. The unintegrated linear viral DNA intermediate that is produced by infection of permissive cells with baboon endogenous virus was isolated. Hybridization with a strong-stop complementary DNA probe demonstrated presence of a terminal repetition in the linear viral DNA. The positions of restriction sites for two particular enzymes, SmaI and XhoI, near each end were consistent with this result and indicated that the length of the repetition is 0.55 +/- 0.01 kilobase. The linear viral DNA had a unique restriction map indicating that it is not a set of random circular permutations of the RNA genome. From hybridization with a 3'-specific probe, the DNA restriction map was aligned relative to the 5'-to-3' orientation of the viral RNA. We observed a minor heterogeneity in a BamHI recognition site 1.95 kilobases from the right end of the linear map.     

Infection of nonhuman primate cells by pig endogenous retrovirus

The ongoing shortage of human donor organs for transplantation has catalyzed new interest in the application of pig organs (xenotransplantation). One of the biggest concerns about the transplantation of porcine grafts into humans is the transmission of pig endogenous retroviruses (PERV) to the recipients or even to other members of the community. Although nonhuman primate models are excellently suited to mimic clinical xenotransplantation settings, their value for risk assessment of PERV transmission at xenotransplantation is questionable since all of the primate cell lines tested so far have been found to be nonpermissive for PERV infection. Here we demonstrate that human, gorilla, and Papio hamadryas primary skin fibroblasts and also baboon B-cell lines are permissive for PERV infection. This suggests that a reevaluation of the suitability of the baboon model for risk assessment in xenotransplantation is critical at this point.     

The breeding and utilization of baboons for biomedical research.

The baboon (Papio cynocephalus) has been used extensively for biomedical research at the Southwest Foundation for Research and Education (SFRE) since 1958. This animal model has adapted well to captivity, has reproduced efficiently, and has proved to be very useful in many areas of medical research. Reproductive data from the SFRE baboon colony, the establishment of a breeding colony from imported animals, the present use of baboons as research models, and the predicted availability and use of these animals were discussed.     

Comparison of blood flow parameters measured by Doppler ultrasound and radionuclide techniques in the baboon (Papio ursinus)

Ascending aortic blood velocity was measured in the baboon (Papio ursinus) by using continuous wave Doppler ultrasound. The blood flow parameters thus obtained were compared to those by the standardized radionuclide technique. It appears that, due to the anatomical position of the ascending aorta and brachiocephalic trunks in relation to the ultrasound beam, Doppler ultrasound does not provide an accurate method of measuring aortic blood velocity in the baboon, which could be the reason for the poor correlation of the results from the two techniques.     

Changes in the gamma chain heterogeneity of hemoglobin F of the baboon (Papio cynocephalus) postnatally and after partial switching to hemoglobin F production by various stimuli

The postnatal switch from hemoglobin (Hb) F to Hb A in the baboon (Papio cynocephalus) occurs somewhat more rapidly than in humans. Minor components which are related to Hb F and Hb A are also present and show reciprocal rise and fall. The baboon produces two types of gamma chain presumably from nonallelic genes. These have either an isoleucyl (I gamma) or a valyl (V gamma) residue in position 75. As in the human case with G gamma and A gamma chains, the ratio I gamma to V gamma chains changes during the postnatal switch. Production of Hb F in the baboon may be stimulated by phenylhydrazine or more effectively by 5-azacytidine. With phenylhydrazine, the ratio of I gamma to V gamma chains in the Hb F is the same as in the traces of Hb F in the juvenile or adult baboon. However, with 5-azacytidine, at least some of the Hb F that is produced probably has been synthesized with an I gamma to V gamma ratio that is present prenatally and in the newborn baboon.     

Discovery of a New Endogenous Type C Retrovirus (FcEV) in Cats: Evidence for RD-114 Being an FcEVGag-Pol/Baboon Endogenous Virus BaEVEnv Recombinant

Analysis of a cat genomic DNA library showed that cats harbor a previously unrecognized endogenous type C retrovirus, whose env gene has homology to the murine Fv-4 resistance gene. This unique retrovirus, designated FcEV (Felis catus endogenous retrovirus), has a type C pol gene, closely related to the primate Papio cynocephalus endogenous virus (PcEV) pol, not overlapping the env gene, unlike in other type C retroviruses, and is presumably present in a higher copy number than RD-114. Phylogenetic analysis of FcEV and RD-114 fragments amplified from cat species and comparison with baboon endogenous virus (BaEV) fragments from monkeys suggested that RD-114 does not represent the cat strain of BaEV but is actually a new recombinant between FcEV type C genes and the env gene of BaEV. Although BaEV did appear to have infected an ancestor of the domestic cat lineage, it was a de novo recombinant that made its way into the cat germ line.     

The isolation of herpesvirus from trigeminal ganglia of normal baboons (Papio cynocephalus).

A herpesvirus was isolated from the trigeminal ganglia of three of six normal baboons (Papio cynocephalus). This virus possessed the virologic characteristics of SA8, A herpesvirus known to be indigenous to the baboon.     

A 4-year summary of the nonsurgical recovery of baboon embryos: A report on 498 eggs

A nonsurgical embryo recovery procedure, developed to allow the economical acquisition of cleavage stage baboon embryos, has been successfully used for 4 years. With this technique, 498 eggs have been recovered from 979 uterine flushes (50.9%) on 71 baboons. Of 467 eggs recovered from mated baboons, 290 (62.1%) were fertilized. Papio anubis females provided a higher percentage of fertilized eggs (75.3%) than did Papio hamadryas (47.8%) or Papio cynocephalus (44.3%) females following exposure to males during estrus, although sexual preference may be responsible for the reduced fertilization rate in the P. cynocephalus females. Recovery rates from individual baboons ranged from 0% (n = 11) to between 66% and 93% for ten baboons from each of which 12–33 eggs have been recovered. Fertilized eggs were at the two-cell (n = 23) to blastocyst (n = 53) stage at recovery 1–6 days postdeturgescence (PD) of the sex skin, with morulae (n = 84) being the most frequent cell stage recovered (30%). The optimum time for performing the procedure was the third day PD, when 113 (40%) embryos were recovered. The abilities of baboons to become pregnant and to provide fertilized embryos were significantly related (P < 0.005), allowing the embryo recovery technique to be used as a screening procedure for evaluating baboon fertility.     

Does space in the jaw influence the timing of molar crown initiation? A model using baboons (Papio anubis) and great apes (Pan troglodytes, Pan paniscus)

Radiographic and histological studies of baboon (Papio hamadryas, P. anubis) and chimpanzee (Pan troglodytes) permanent tooth development have found that periods of molar crown mineralization overlap markedly in chimpanzees but are staggered in baboons. Here we test the hypothesis that these intertaxon differences in molar initiation are primarily due to the space available in the mandibles of each species for these teeth. This study includes radiographic, linear measurement, and three-dimensional (3D) coordinate landmark data taken from baboon (Papio anubis n=51) and great ape (Pan paniscus n=43, P. troglodytes n=60) mandibles and permanent molars across a broad developmental range for each taxon. Unexpectedly, 3D multivariate statistical shape analysis of the molar crypt, crown, and root data shows that all three species trajectories of molar row shape change are indistinguishable from each other. Qualitative analysis of these 3D data reveals subtle and inconclusive intergeneric differences in the space maintained between adjacent molars during growth. The space distal to each newly initiated molar is slightly greater in the baboon. Bivariate analyses comparing molar row and mandibular corpus proportions in Papio and Pan fail to show clear or consistent taxonomic differences in the ratio of space afforded developing molars in the alveolar bone. Thus, there is a poor correlation between mandibular proportion and both intermolar spacing and 3D molar development pattern. Contrary to earlier studies, these results suggest that pattern of molar crown initiation and temporal overlap of adjacent mineralizing crowns is not significantly different between Papio and Pan. This may be due in part to the inclusion here of not only 3D molar crown data but also 3D molar crypt data. This study strongly refutes the hypothesis that space available in the mandible directly underlies different times of permanent molar crown initiation between Papio and Pan.     

Distribution of distinct arachidonoyl-specific and non-specific isoenzymes of diacylglycerol kinase in baboon (Papio cynocephalus) tissues.

We investigated the diacyglycerol kinase species present in several baboon tissues using the substrates sn-1-stearoyl-2-arachidonoyl diacylglycerol and sn-1,2-didecanoyl diacylglycerol. Chromatography of octyl glucoside extracts of the baboon (Papio cynocephalus papio) tissues on hydroxyapatite columns revealed the presence of three diacylglycerol kinase species with different substrate preferences. One species markedly 'preferred' the substrate sn-1-stearoyl-2-arachidonoylglycerol, the two other species preferred sn-1,2-didecanoylglycerol. Measurement of the activity of the baboon brain diacylglycerol kinases toward diacylglycerols with a range of different fatty acid chains revealed a strict preference of the arachidonoyl diacylglycerol kinase for sn-1-acyl-2-arachidonoyl diacylglycerol, whereas the other enzymes showed no preference toward several long-chain-fatty-acid-containing diacylglycerols. The arachidonoyl diacylglycerol kinase was particularly abundant in brain and testis, whereas liver was practically devoid of this enzyme. The arachidonoyl diacylglycerol kinase from baboon brain was found to be predominantly associated with the particulate fraction and exhibited an apparent molecular mass of 130 kDa.     

Intestinal Protozoa of the Baboon Papio doguera Pucheran, 1856

SYNOPSIS. Broad scope investigations have allowed a study of the intestinal parasitic protozoa of the Kenya baboon Papio doguera in its natural habitat as well as an opportunity to follow the intestinal protozoan populations in these primates held in captivity. Samplings indicate that the amoebae found in the baboon are essentially the same as those which commonly occur in man. Balantidium coli is frequent in wild baboons but is self-limiting in animals after a few weeks in captivity. The flagellates Chilomastix mesnili and Giardia lamblia were detected in captive but not in wild baboons; the presence of the latter constitutes a new record for Papio doguera.     

Immigration of aPapio anubis male into a group ofPapio cynocephalus baboons and

The 1982 observation of the immigration of an adult male olive baboon, Papio anubis,into a group of yellow baboons, Papio cynocephalus,in Amboseli National Park, Kenya, constitutes the first confirmed report of interbreeding between the two species within the Amboseli baboon population. We document the social aspects of the immigration and describe subsequent sightings of anubisbaboons in Amboseli that confirm the existence of a previously unrecognized hybrid zone in Kenya.