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Characterization of a human gene conferring sensitivity to infection by gibbon ape leukemia virus.

Gibbon ape leukemia virus (GALV) enters cells following interaction with a specific receptor protein. We have isolated human complementary DNAs (cDNAs) encoding a protein which, when expressed in normally uninfectable mouse NIH3T3 cells, confers on these cells specific sensitivity to infection by GALV. This was done by transfection into mouse cells of human DNA and selection of putative receptor gene transfectants using infection with a retrovirus carrying a drug resistance gene. Transfected genomic sequences were then cloned through their association with repetitive DNA, and these were used to isolate cDNA clones. The predicted 679-amino acid sequence encoded in these cDNAs is characteristic of an integral membrane protein in that multiple potential transmembrane domains are present. Searches of DNA and protein data banks failed to reveal homologies to other known sequences. It thus appears that the sequence isolated is novel and represents the human receptor for GALV. As expected from the wide host range of the virus, closely related homologues of the gene were found in several other vertebrate species tested.

Amino Acid Sequence↗

Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells.

The study of the expression of alpha-galactosyl epitopes on various mammalian cells is of particular interest, since as much as 1% of circulating IgG antibodies in humans interact with this carbohydrate residue. This natural antibody, designated "anti-Gal," was previously found to bind to terminal Gal alpha 1----3Gal beta 1----4GlcNAc-R on biochemically defined glycolipids (Galili, U., Macher, B. A., Buehler, J., and Shohet, S. B. (1985) J. Exp. Med. 162, 573-582; Galili, U., Buehler, J., Shohet, S. B., and Macher, B. A. (1987) J. Exp. Med. 165, 693-704). The expression of anti-Gal binding epitopes on nucleated cells from various mammalian species was studied by immunostaining with this antibody. The binding of anti-Gal to various cells was correlated with the binding of the lectin Bandeiraea (Griffonia) simplicifolia IB4 (BS lectin). The BS lectin also interacts with alpha-galactosyl residues and particularly with high affinity with Gal alpha 1----3Gal beta 1----4GlcNAc residues. We observed a striking evolutionary pattern in the expression of these epitopes on mammalian nucleated cells. Fibroblasts, epithelial cells, endothelial cells, smooth muscle cells, and lymphoid cells of nonprimate mammals, prosimians, and New World monkeys readily bound both anti-Gal and BS lectin. However, no such binding was detectable on cells of Old World monkeys, apes, and humans. Measurment of the binding of radiolabeled BS lectin to the various nucleated cells suggests that cells binding anti-Gal express 10(6) to 3.5 x 10(7) alpha-galactosyl epitopes, most of which, based on the anti-Gal specificity, seem to have the structure of Gal alpha 1----3Gal beta 1----4GlcNAc-R. The absence of these epitopes from human cells results from diminished activity of the enzyme alpha 1----3 galactosyltransferase, which catalyzes the following reaction. Gal beta 1----4GlcNAc-R + UDP-Gal(alpha 1----3-galactosyltransferase)----Gal alpha 1----3Gal beta 1----4GlcNAc-R + UDP This enzyme, which participates in the glycosylation of cell membrane glycoconjugates in nonprimate mammals, prosimians, and New World monkeys, appears to have been suppressed in Old World primates as a result of evolutionary events which occurred 20-30 million years ago. It is argued that an anomalous activity of this enzyme in man may result in initiation of autoimmune diseases because of the de novo expression of Gal alpha 1----3Gal beta 1----4GlcNAc-R epitopes recognized by anti-Gal.

ABO Blood-Group System↗

The chemical restraint of apes and monkeys by means of phencyclidine or ketamine.

The anesthetic effects of two drugs, namely, Phencyclidine and Ketamine, used alone or in combination with atropine, were compared during clinical and experimental procedures on different primate species ranging from gorillas, orangutans, white-faced and dwarf chimpanzees, baboons, cercopithecus monkeys to new--world monkeys. It is concluded that both these anesthetics are very good and safe drugs for restraint and anesthesia. Ketamine appeared to be superior to Phencyclidine for use among apes and monkeys in so far as it is shorter acting, has wider safety margin and shorter recovery time, provides better muscle relaxation and is practically without side effects. But Phencyclidine has definite advantage in so far as it is needed is smaller quantity to produce comparable effect of anesthesia.

Animals↗

[Viral hepatitis A and B in anthropoid apes of the Moscow Zoo].

The rate of occurrence of hepatitis A and B virus specific markers in anthropoid apes of the Moscow Zoo (3 chimpanzees, 3 gorillas, 8 orang-outangs) was studied. Long-term persistence of HBs-antigen in orang-outang accompanied by the presence of HBe-antigen and anti-HBs was demonstrated. The presence of anti-HBs in gorillas and orang-outangs was recorded. Antibodies to hepatitis A virus were found in all the animal species examined. Cases of acute virus hepatitis A in orang-outangs are described contracted from the personnel handling the animals and suffering from this type of hepatitis. Morphological features of the course of hepatitis A in the presence of HBs-antigen carrier state are described. The possibility of active immunization of susceptible animals and the personnel of the zoo against viral hepatitides is discussed.

Animals↗

Studies on the specificity of human antibodies reacting with GP70 and P15 antigens of baboon endogenous (BaEV) and gibbon ape leukaemia (GaLV) viruses.

Antibodies reacting with gp70 and p15 antigens of baboon endogenous virus (BaEV) and gibbon ape leukaemia virus (GaLV) were detected by radioimmunoprecipitation (RIP) in blood plasma samples of patients with chronic granulocytic leukaemia, acute myeloid leukaemia and with potentially preleukaemic haematological disorders. Anti-gp70 antibodies were found more frequently than anti-p15 antibodies. Digestion of the carbohydrate part of gp70 antigens by glycosidase treatment abrogated the precipitation mediated by IgM antibodies, whereas that mediated by IgG antibodies was not markedly affected. Data suggest that antibodies detected in human plasma samples may have oncovirus specificity, but in considerable part of cases they can be of heterophil nature.

Animals↗

Restricted expression of retrovirus nucleic acids and proteins in primate type C virus (gibbon ape leukemia virus-simian sarcoma virus)-initiated human B-lymphoblast cultures.

Fresh human B-lymphoblasts established in culture following exposure of adult peripheral blood leukocytes to type C retroviruses of the simian sarcoma virus/simian sarcoma-associated virus-gibbon ape leukemia virus group were analyzed in detail for the presence of the infecting virus. Viral expression ranged from production of low levels of intact virus in a few cultures to the presence of viral RNA and protein in the absence of detectable of levels of complete virus in the majority of the cultures. In situ molecular hybridization assays using 3H-labeled complementary DNA and indirect immunofluorescence assays using antibody to purified viral protein indicated that the expression of viral RNA and proteins are preferentially expressed in only a fraction of the cells in some cultures. If expression of the infecting viral sequences is necessary for the sustained growth of these cells, then those cells detectably synthesizing viral RNA and proteins may be influencing the growth of the remaining virus-negative cells. The lack of virus production in cultures synthesizing viral RNA and protein indicate that these human B-lymphocytes restrict the life cycle of these viruses at some step(s) after transcription of viral RNA or translation of viral protein.

B-Lymphocytes↗

Antistreptococcal antibodies, rheumatoid factors and haptoglobin in apes and monkeys.

Sera of 157 baboons (Papio hamadryas and P. anubis) 21 chimpanzees (Pan troglodytes) five orang utans (Pongo pygmaeus) three mountain gorillas (Gorilla gorilla beringei) and three gibbons (Hylobates lar lar) were examined for the content of antistreptolysin O, antidesoxyribonuclease B, for the presence of rheumatoid factors as well as for the level and type of haptoglobin. The mean antistreptolysin O titer (AST) in baboons was 106 ASU +/- 18 in dextransulfate absorbed sera ("real" AST) and 182 ASU +/- 34 in non-absorbed sera. The mean decrease after absorption was 20% (i.e., 20% inhibitor + 80% antistreptolysin O), a value that is lower than previously found in rhesus monkeys (55%) or in man (40%). Raised values of anti-DNase B were found in two baboons only, and none of the sera of that species displayed presence of rheumatoid factors. In chimpanzees, the mean AST was 68 +/- 29 in absorbed and 87 ASU +/- 57 in non-absorbed sera. Anti-DNase B was raised in three animals, and in two cases the increase was correlated with raised AST. Of 19 chimpanzee sera examined, 13 were found to contain antigammaglobulins ("rheumatoid factors") the titers of which reached 1:64 or more. All primate sera tested so far showed haptoglobin type 1-1 or Hp 1-1-like patterns. The haptoglobin level in chimpanzees and baboons was comparable to that established in man; in rhesus monkey, on the other hand, much lower values (40-62 mg/100 ml) or ahaptoglobinemia were observed. The sera of all monkeys and apes tested so far showed a very low (undiluted, or up to 1:10 titer at most) agglutinating activity against T4-antigen-carrying streptococci. This is in agreement with our observations made previously which indicated that human or animal sera of haptoglobin type 1-1 agglutinated streptococci to a much lower degree than type Hp 2-2 or type Hp 2-1 sera.

Animals↗

Chromosomal evolution of the great apes and man.

A study of all the chromosomal changes that have occurred during evolution of the great apes and man gives an indication of the phylogeny of these species. Their karyotypes differ from one another by a dozen chromosomal changes. The karyotype of their ancestor was very similar to that of living orangutans. Reconstruction of the sequence of the chromosomal changes indicates that, after the isolation of the orang-utan, a common ancestral population existed for the other species. Then, each branch leading to the living genera was independently isolated. The karyotype of the chimpanzee is an intermediary stage between that of man and the gorilla for some chromosomes. The human karyotype is less differentiated than that of the chimpanzee or the gorilla.

Animals↗

Infectious diseases of the great apes of Africa.

The chimpanzee is the most extensively used ape in biomedical research. Its phylogenetic relationship to man has made it one of the most desirable of research animals. However, because of this closeness to man, the chimpanzee is highly susceptible to human (and other primate) infectious agents, particularly viruses. This susceptibility makes the chimpanzee the only known available test system for aetiological studies on such diseases as hepatitis, neurological diseases of suspected viral origin, etc. Very few infectious disease data are available on the gorilla. What is known suggests a parallelism with the chimpanzee and man. Serological data, however, strongly suggest that subclinical infection without overt disease occurs following contact with human and other animal infectious agents. The need for studies of infectious diseases in the wild is stressed. The susceptibility of these species to human disease incitants emphasizes the need for rigid precautions to avoid exposure and to maintain healthy animals.

Animals↗

Chromosomes and spermatozoa of the African great apes.

We have analysed the chromosome constitution of 8 chimpanzees (Pan troglodytes), 3 pygmy chimpanzees (Pan paniscus), and 16 gorillas (Gorilla gorilla). In the chimpanzees, the frequency of brilliant Q-band polymorphisms accounted for 8.85 regions per individual, and in the gorilla 14.9, whereas in man it was only 2.9-4.6. Variation in the amount of constitutive heterochromatin was also observed, and the gorilla appeared to be the most variable of all. A detailed analysis of the spermatozoa of the African apes showed that the gorilla produced pleiomorphic spermatozoa. As the animals under investigation were phenotypically normal, of proven fertility, and were kept in unheated cages, it is probable that gorillas, like human males, normally exhibit pleiomorphic spermatozoa. This makes it unlikely that clothing-induced hyperthermia could account for pleiomorphic spermatozoa in man. The modal cell types in the ejaculates of men and gorillas were also morphologically identical. The less frequent cell types defined as morphologically abnormal spermatozoa were also very similar and occurred in similar proportions. It is therefore impossible to distinguish between man and the gorilla by a simple examination of the ejaculate, although it is possible to distinguish between man and the chimpanzees or between the gorilla and the chimpanzees. Both species of chimpanzee produced identical spermatozoa. With quinacrine fluorescence, F-bodies were observed in the sperm head of the chimpanzees and the gorilla. In the chimpanzee and the pygmy chimpanzee, F-bodies correspond to brilliant autosomal regions, whereas in the gorilla they probably correspond both the the autosomes and the Y chromosome. There was no consistently visible F-body in the sperm head of the chimpanzee or the gorilla; in the pygmy chimpanzee, one fluorescent region appeared, and it probably corresponded to a brilliant region in autosomal pair No. 23.

Animals↗

Perinatal listeric septicemia in a Celebese black ape.

Perinatal listeric septicemia was diagnosed in a still-born Celebese black ape (Macaca niger). The disease was characterized by prominent focal hepatic necrosis and a diffuse, acute, fibrinopurulent placentitis. Small, gram-positive rods were demonstrable in sections of the placenta and in the liver and lungs of the fetus. Listeria monocytogenes 1A was isolated from the liver of the fetus.

Animals↗

Ovarian carcinoma with transcelomic metastasis in a Barbary ape.

An ovarian carcinoma, unique among those recorded from nonhuman primates inasmuch as it contained psammoma bodies and ciliated epithelium, was found in a Barbary ape. The tumor was characterized by transcelomic metastasis, a feature common to ovarian and uterine tube malignancies of women.

Abdomen↗

Regulation of interleukin-2 and interleukin-4 receptor expression in human and ape lymphoid cell lines.

In this study, we have analyzed the expression and regulation of receptors for IL-2 (alpha and beta chains) and IL-4 in four lymphoid cell lines established from leukemic cells. The gibbon ape cell line MLA 144 was the only one to express constitutively the IL-2R beta chain and IL-4R, whereas the NK-like YT cells express only IL-2R beta. The two other cell lines in this study, PEER and HSB2, are derived from T lymphocytes, and express neither IL-4R, IL-2R beta, nor IL-2R alpha unless stimulated. We report here that those receptors that are constitutively expressed, i.e., IL-2R beta on YT cells and IL-2R beta or IL-4R on MLA cells, are down-regulated by stimulation with PHA + PMA. In contrast, RNase protection experiments showed that PHA + PMA stimulation of T cell lines induces mRNA for all three receptors in PEER cells, and only IL-2R alpha and IL-4R in HSB-2. Thus each of these three receptors is subjected to a different regulation, which in addition varies depending on the lineage (or differentiation stage) of the cells. This was further supported by the finding that IL-1 alpha or TNF-alpha regulates these receptors differently. These two cytokines have no effect on IL-2R beta and IL-4R in MLA and YT, but induce IL-2R alpha in YT. In contrast, they do not induce either chains of the IL-2R in the T cell lines PEER or HSB-2, but TNF induces IL-4R mRNA in HSB2 cells, and IL-1 does so in both cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[The forms of cognitive activity in monkeys and apes].

Cognitive functions were compared in three species of primates (Cebus apella, Macaca mulatta, Pan troglodytes). Under identical conditions, studies have been made on the ability of identify two-dimensional natural images corresponding to three-dimensional objects basing on a modified "sample-to-sample" method. It was shown that monkeys learned to solve these tasks via multilevel combination of visual pictures with voluminous objects, being able to translate the principle elaborated from one set of stimuli to another. Apes exhibit the ability of direct translation of two-dimensional objects to three-dimensional ones using former experience in solving new tests of various complexity.

Animals↗

Zinc toxicosis in a Celebes ape (Macaca nigra) following ingestion of pennies.

An adult Celebes ape (Macaca nigra) was presented for a routine yearly evaluation. Abdominal radiographs revealed four radiodense metallic foreign objects resembling coins within the gastrointestinal tract. Hematologic abnormalities included a mild nonregenerative anemia and a mild leukocytosis, and the biochemical profile reflected renal dysfunction. Serum zinc levels were elevated. The animal was denied food for 24 hr in preparation for the endoscopic removal of the foreign objects. During this period, two partially eroded pennies were passed in the feces. Endoscopy was temporarily postponed, and the animal was offered food. Two days later a third penny was passed. When the fourth coin did not pass within the next 2 days, the animal was once again denied food, and the fourth coin was passed within 24 hr. Because of the temporal association between the fasting cycles and the passage of the coins, a causal relationship is suggested. Following the passage of all coins, serum zinc levels decreased, and hematologic and serum biochemical abnormalities improved. Six months later, all abnormalities had resolved.

Animals↗