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At least 19 recordsLinked to original sources
PubMed1989

Intestinal trichomonads (Tritrichomonas mobilensis) in the natural host Saimiri sciureus and Saimiri boliviensis.

A retrospective study of cecal and colonic tissues from 28 squirrel monkeys (Saimiri sciureus and Saimiri boliviensis) demonstrated enteric trichomonads within luminal crypts. Twenty-one of 28 (75%) had trichomonads in the mucosal epithelium either in cup-like depressions or intraepithelial vacuoles. Organisms were also beneath the superficial luminal mucosal epithelium and between the basement membrane and crypt epithelial cells. Immunoperoxidase staining also identified organisms within the lamina propria and submucosa. Additional histologic changes included mucosal ulceration, multifocal cryptitis, and focal epithelial necrosis. Most areas containing trichomonads did not have an associated inflammatory response.

Animals↗
PubMed1988

Elevation in plasma glucagon levels in response to stress in squirrel monkeys: comparisons of two subspecies (Saimiri sciureus boliviensis and Saimiri sciureus sciureus).

Bolivian (Bo) and Brazilian (Br) squirrel monkeys (SMs) were captured and restrained to determine patterns of glucagon and glucose response. In both subspecies, plasma glucagon and glucose levels rose rapidly in response to restraint procedures; glucagon levels in BrSMs and glucose levels in both subspecies returned to basal values in 15 minutes. The magnitude of the glucagon and glucose responses differed significantly between BoSMs and BrSMs.

Animals↗
PubMed1975

Spontaneous Herpesvirus saimiri lymphoma in owl monkeys.

Three examples of spontaneous malignant lymphoma were observed in owl monkeys 23, 81, and 183 days after arrival in our laboratories. The pathological features of the disease were analogous to experimentally induced Herpesvirus saimiri lymphoma. H. saimiri was recovered from 2 animals (it was not attempted from one case) and one isolate was shown to reproduce characteristic H. saimiri malignant lymphoma. Each monkey originated in Peru in contrast to our usual source of owl monkeys which originate in Barranquilla, Colombia. Samples collected from owl monkeys in Peru did not reveal antibodies to H. saimiri nor were virus isolated from cocultured leukocytes. Squirrel monkeys in the same geographical location all carried H. saimiri. The observations indicate that H. saimiri lymphoma can occur as a spontaneous disease and that the virus can cross the same taxonomic lines in nature as in the laboratory.

Animals↗
PubMed1976

Studies of cultured lymphocytes of the owl monkey (Aotus trivirgatus) infected with Herpesvirus saimiri.

The lymphocytes of five owl monkeys (Aotus trivirgatus) infected with Herpesvirus saimiri and three control monkeys were studied. Lymphocytes were separated on Ficoll-Hypaque gradients, incubated in suspension cultures, and prepared for electron microscopic and immunofluorescent study at 24, 48, and 72 hours after the beginning of culture. Buffy coats of whole blood obtained immediately after bleeding were also prepared for study. At the time of the study, four of the five infected monkeys had died with malignant lymphoma and lymphocytic leukemia. Herpesvirus saimiri virions were demonstrated by electron microscopy and H saimiri antigens by immunofluorescence in 1-20% of the lymphocytes from infected monkey in two of five cultures at 24 hours after culture, four of five at 48 hours after culture, and all of five at 72 hours after culture. There was good agreement between the electron microscopic and the immunofluorescent data. None of the control monkey cultures and none of the buffy coat preparations contained H saimiri virions or antigens. By electron microscopy, the great majority of the virus particles were nucleocapsids within the nuclei of lymphocytes. Enveloped virions were seldom observed. There was some evidence to suggest that the higher the percentage of lymphocyte containing H saimiri, the poorer the prognosis for the monkey. Herpesvirus saimiri was isolated from all five infected monkeys by co-cultivation of lymphocytes with Vero cells. Control lymphocyte co-cultivations were negative.

Animals↗
PubMed1990

Functional characterization of the antibody-mediated protection against blood stages of Plasmodium falciparum in the monkey Saimiri sciureus.

The squirrel monkey Saimiri sciureus is one of the World Health Organization recommended experimental models of Plasmodium falciparum blood stage infection. Anti-malaria antibodies developed by this host after a drug-controlled infection play an important part in the acquired protection against the P. falciparum blood stages. Furthermore, the use of two anti-Saimiri immunoglobulin (Ig) monoclonal antibodies (mAb) has permitted the differentiation between protective (mAb 3A2/G6) and non-protective (mAb 3E4/H8) antibodies, as shown by transfer experiments to recipient monkeys infected with blood stage parasites. In the present study we have established that protection conferred by the 3A2/G6+ protective Ig preparation is strictly associated with an in vitro opsonic activity. Such an opsonic activity is not detectable in the 3E4/H8+ non-protective Ig population. In addition, results indicate that the 3E4/H8+ non-protective Ig population competes with protective opsonic 3A2/G6+ Ig antibodies when co-incubated with parasitized red blood cells. Thus, it follows that protection can be directly correlated to the quantitative and qualitative fluctuation of the two Ig populations. When challenged with 1 x 10(8) P. falciparum-infected Saimiri red blood cells parasitemia occurred in 5 out of 12 Saimiri who were lacking detectable 3A2/G6+ opsonic antibodies in their sera. By employing antibodies against the human Fc receptor for IgG (Fc gamma R) in an in vitro phagocytic assay, we have been able to show that the principal receptor is Fc gamma RIII. Finally, we also show that in contrast to the situation in man, this receptor is present on circulating monocytes. These findings could lead to a different strategy in designing malaria vaccine candidates and also allow the possibility of predicting the outcome of immunization trials in Saimiri monkeys.

Animals↗
PubMed1975

Experimental horizontal transmission of Herpesvirus saimiri from squirrel monkeys to an owl monkey.

Herpesvirus saimiri was naturally transmitted from squirrel monkeys excreting the virus to one of two owl monkeys housed in the same cage. The owl monkey became infected approximately three months after contact was initiated. H. saimiri was consistently isolated from the peripheral lymphocytes until this animal died eight months later. During this period the owl monkey developed specific antibody to H. saimiri to a maximal neutralization index of 5.5 logs. The other monkey remained uninfected for an ovservation period of one year. The documentation of this horizontal transmission of H. saimiri infection from squirrel monkeys to an owl monkey suggests that owl monkeys developing spontaneous malignant lymphomas associated with H. saimiri infection may also have acquired the infection in this manner.

Animals↗
PubMed1992

Mechanisms of protective immunity against asexual blood stages of Plasmodium falciparum in the experimental host Saimiri.

In the Saimiri monkey, an experimental host for human malaria, acquired protection against Plasmodium falciparum blood stages depends on the IgG antibody populations developed. In vivo protective anti-falciparum activity of IgG antibodies is correlated with the in vitro opsonizing activity promoting phagocytosis of parasitized red blood cells. In contrast, non protective antibodies inhibit this mechanism by competing at the target level. A similar phenomenon can be observed in human infection. Anti-cytoadherent and anti-rosette antibodies developed by Saimiri and humans prevent the development of physiopathological events like cerebral malaria which can also occur in this experimental host. Furthermore, transfer to protective human anti-falciparum IgG antibodies into infected Saimiri monkeys exerts an anti parasite activity as efficient as that observed when it is transferred into acute falciparum malaria patients, making the Saimiri an even more attractive host. Studies on the role of immunocompetent cells in the protective immune response are still in their infancy, however the existence of a restricted polymorphism of MHC II class molecules in the Saimiri confers additional theoretical and practical importance to this model.

Animals↗
PubMed1992

Platelet kinetics and other hematological profiles in experimental Plasmodium falciparum infection: a comparative study between Saimiri and Aotus monkeys.

Levels of platelets and other hematological values were monitored in 21 Saimiri and 12 Aotus monkeys over a period of three weeks post-infection with monkey-adapted Indochina CDC-1 strain of Plasmodium falciparum. In both Saimiri sciureus boliviensis and Aotus nancymai karyotype-1 monkeys the severest thrombocytopenia was observed at 14 days post-infection coinciding with peak parasitemia, neutropenia, lymphocytosis, and anemia associated with severe hemoglobinemia and elevated fibrinogen degeneration products(FDP's). MCH and MCV profiles in Aotus monkeys decreased with ascending parasitemia. In contrast, these parameters in Saimiri were characterized by a significant compensatory increase correlating with parasitemia. In general, thrombocytopenia was one of the earliest clinical manifestations of the infection with the platelets returning to normal levels shortly after peak parasitemia at 14 days. Platelet kinetics had a strong correlation with hematologic and parasitologic values in the Aotus model. No consistent associations were observed between platelet kinetics and other parameters in the Saimiri model. These data indicate that the Aotus model for malaria is more predictable than the Saimiri. Further, platelet turnover rates and recovery provide a useful prognostic parameter during malaria infection. The results are discussed in relation to the value of the two species of monkeys as models for the pathogenesis of human malaria.

Animals↗
PubMed1985

A transcription enhancer in the Herpesvirus saimiri genome.

Herpesvirus saimiri, an oncogenic agent of New World primates, has a linear double-stranded DNA genome of approximately 155 kb. To test its genome for the presence of a transcription enhancer, we have mixed randomly fragmented H. saimiri DNA with non-infectious, linear SV40 DNA lacking the 72-bp repeat enhancer region (the so-called SV40 enhancer trap) and co-transfected this DNA mixture into monkey CV-1 cells. Viable SV40-like viruses were generated by intracellular ligation/repair processes with short H. saimiri DNA fragments. One recombinant, SVHS-2, had integrated a 377-bp enhancer segment from the righthand region of the H. saimiri genome, 7 kb upstream of DNA sequences encoding an immediate-early mRNA. This enhancer sequence is contained within the non-repetitive portions of the viral genome known to be preserved episomally in all lymphoid tumor cell lines. Further recombinant viruses (SVHS-14, SVHS-7, and SVHS-8) essentially contain subsets of the 377-bp insert. Unlike in the previous enhancer trap experiments, where heterologous enhancers were incorporated without any sequence alterations, SVHS-14 and SVHS-7 have suffered short internal deletions of a very similar segment of the H. saimiri insert. This renders the enhancer more active, implying that the deleted segment, while it may have a role in the herpesvirus infection cycle, exerts a negative effect within the isolated enhancer.

Antigens, Viral, Tumor↗
PubMed1977

Episomal viral DNA in a Herpesvirus saimiri-transformed lymphoid cell line.

The lymphoid cell line #1670 has been derived from the infiltrated spleen of a tumor-bearing marmoset monkey infected with Herpesvirus saimiri. The cells contain both types of H. saimiri DNA, unique light (L-) DNA (36% cytosine plus guanine) and repetitive heavy (H-) DNA (71% cytosine plus guanine), without producing infectious virus. Viral DNA was found to persist in these cells as nonintegrated circular DNA molecules. Closed circular superhelical viral DNA molecules were isolated by three subsequent centrifugation steps: (i) isopycnic centrifugation in CsCl, (ii) sedimentation through glycerol gradients, and (iii) equilibrium centrifugation in CsCl-ethidium bromide. The isolated circles had a molecular weight of 131.5 +/- 3.6 x 10(6). This is significantly higher than the molecular weight of linear DNA molecules isolated from purified H. saimiri virions (about 100 x 10(6)). Partial denaturation mapping of circular molecules from #1670 lymphoid cells showed uniform arrangement of H- and L-DNA sequences in all circles. All denatured molecules contained two L-DNA regions (molecular weights of 54.0 +/- 1.8 x 10(6) and 31.5 +/- 1.3 x 10(6)) and two H-DNA regions (molecular weight of 25.6 +/- 1.9 x 10(6) and 20.0 +/- 0.8 x 10(6)) of constant length. Maps of both L-regions suggested that the sequences of the shorter L-DNA region were a subset of those of the longer region. The sequences of both L-regions had the same orientation. Circular molecules from H. saimiri-transformed lymphoid cell line #1670 appeared to represent defective genomes, containing only 75% of the genetic information present in L-DNA of H. saimiri virions.

Animals↗
PubMed1986

Nononcogenic deletion mutants of herpesvirus saimiri are defective for in vitro immortalization.

Herpesvirus saimiri L-DNA sequences between 0.0 and 4.0 map units (4.5 kilobase pairs) are required for oncogenicity; these sequences are not required for replication of the virus. To investigate the basis for the lack of oncogenicity of mutants with deletions in this region and to study the function of this region, we developed a reliable system for in vitro immortalization by herpesvirus saimiri. In contrast to peripheral blood lymphocytes from cotton-top tamarins (Saguinus oedipus) and owl monkeys (Aotus sp.), infection of peripheral blood lymphocytes from common marmosets (Callithrix jacchus) in vitro with herpesvirus saimiri consistently yielded continuously growing lymphoblastoid cell lines. Such cell lines were established using strains of herpesvirus saimiri from group A and group non-A, non-B; however, repeated attempts to immortalize common marmoset peripheral blood lymphocytes using strains from group B were not successful. Common marmoset cell lines immortalized by herpesvirus saimiri were T12+, T8+, T4-, and B1-, indicating that they were derived from suppressor/cytotoxic T lymphocytes. Cell lines could not be established using the nononcogenic mutants 11att and S4, both of which were derived from the group A strain 11 virus. Strain 11att has a spontaneous deletion and S4 has a constructed deletion in the 0.0 to 4.0 map unit region. Constructed strains which had these deleted sequences restored did immortalize common marmoset peripheral blood lymphocytes. Thus, the nononcogenic deletion mutants are defective for immortalization. This system should facilitate attempts to define the sequences responsible for immortalization and to determine their function.

Animals↗
PubMed1986

Organization of the thymidylate synthase gene of herpesvirus saimiri.

Herpesvirus saimiri codes, unlike most other herpesviruses, for a thymidylate synthase (TS). The TS gene of herpesvirus saimiri is unusual in structure and regulation of expression. It is transcribed into a nonspliced mRNA of 2,190 nucleotides. The single open reading frame of the viral TS gene, instructing a polypeptide of 33.5 kilodaltons, has extensive sequence homology with the corresponding TS coding sequences of human cells and of various procaryotes; the putative polypeptide derived from the nucleotide sequence of the herpesvirus saimiri TS gene is 70% identical with the human enzyme. The untranslated regions of the herpesvirus saimiri TS gene do not share homology with the other characterized eucaryotic or bacterial TS genes. The 5' untranslated sequence has 22 ATG triplets shortly followed by stop codons. The herpesvirus saimiri TS gene, which may be weakly transcribed during immediate early and early times of virus replication, is maximally expressed at the late phase. Various parameters suggest that the TS gene has been acquired in virus evolution by an ancestral herpesvirus from the cellular genome.

Amino Acid Sequence↗
PubMed1987

In vitro immortalization of marmoset cells with three subgroups of herpesvirus saimiri.

Sequences within the rightmost 7 kilobases of the unique L DNA of herpesvirus saimiri are required for oncogenicity of the virus. The same DNA region has been found to be highly variable among different strains of herpesvirus saimiri. On the basis of this variability, herpesvirus saimiri strains were classified into groups A, B, and non-A, non-B. Herpesvirus saimiri strains representing the three groups were used successfully for in vitro immortalization of phytohemagglutinin-activated, interleukin 2 (IL-2)-expanded peripheral blood lymphocytes of common marmosets (Callithrix jacchus). Peripheral blood leukocytes could be immortalized from only a subset of common marmosets (5 of 13). All of the immortalized cell lines contained covalently closed circular viral DNA molecules and initially showed a low level of virus production. Cells immortalized by group A and group non-A, non-B strains did not require IL-2 in the medium. However, the only group B immortalized cell line, 473-SMHI, did not grow well in the absence of IL-2. The different characteristics of cell lines immortalized by herpesvirus saimiri strains belonging to different groups may help to elucidate some functions coded by the highly variable DNA region which is involved in the oncogenic process.

Animals↗
PubMed1992

Primary structure of the herpesvirus saimiri genome.

This report describes the complete nucleotide sequence of the genome of herpesvirus saimiri, the prototype of gammaherpesvirus subgroup 2 (rhadinoviruses). The unique low-G + C-content DNA region has 112,930 bp with an average base composition of 34.5% G + C and is flanked by about 35 noncoding high-G + C-content DNA repeats of 1,444 bp (70.8% G + C) in tandem orientation. We identified 76 major open reading frames and a set of seven U-RNA genes for a total of 83 potential genes. The genes are closely arranged, with only a few regions of sizable noncoding sequences. For 60 of the predicted proteins, homologous sequences are found in other herpesviruses. Genes conserved between herpesvirus saimiri and Epstein-Barr virus (gammaherpesvirus subgroup 1) show that their genomes are generally collinear, although conserved gene blocks are separated by unique genes that appear to determine the particular phenotype of these viruses. Several deduced protein sequences of herpesvirus saimiri without counterparts in most of the other sequenced herpesviruses exhibited significant homology with cellular proteins of known function. These include thymidylate synthase, dihydrofolate reductase, complement control proteins, the cell surface antigen CD59, cyclins, and G protein-coupled receptors. Searching for functional protein motifs revealed that the virus may encode a cytosine-specific methylase and a tyrosine-specific protein kinase. Several herpesvirus saimiri genes are potential candidates to cooperate with the gene for saimiri transformation-associated protein of subgroup A (STP-A) in T-lymphocyte growth stimulation.

Amino Acid Sequence↗
PubMed1991

Identification of transforming genes of subgroup A and C strains of Herpesvirus saimiri.

Herpesvirus saimiri is an oncogenic herpesvirus that induces rapidly progressing lymphomas in New World primates. Using retrovirus vectors for gene transfer, specific open reading frames of H. saimiri were tested for their ability to transform rodent cells in culture. One open reading frame, designated STP-C488 (for saimiri-transformation-associated protein of the subgroup C strain 488), phenotypically transformed Rat-1 cells, resulting in formation of foci, growth at reduced serum concentration, and growth to higher cell densities. Cells transformed by STP-C488 formed invasive tumors in nude mice. The STP-A11 reading frame of strain 11 (subgroup A) was much less potent in its transforming ability than STP-C488. These results demonstrate the oncogene nature of these two open reading frames and provide a means for studying their transforming functions independent of the rest of the H. saimiri genome.

Animals↗
PubMed1991

Persistence of selectable herpesvirus saimiri in various human haematopoietic and epithelial cell lines.

Herpesvirus (h.) saimiri, an infectious agent of squirrel monkeys, is capable of persisting in T lymphocytes of various primate species. It has been used as a vector for the functional analysis of regulatory genes in primary human T lymphocytes. As it is not yet known whether other cell types are capable of supporting viral persistence, various human cell lines were investigated using selectable h. saimiri recombinants. The lines chosen represent cells from the epithelium and connective tissue as well as from all haematopoietic lineages, i.e. cells of B and T lymphoid origin as well as myeloid-, fibroblast- and carcinoma-derived cultures converted to Geneticin or hygromycin B resistance, and harbouring episomal DNA of the selectable recombinants. The Burkitt's lymphoma-derived cell line Raji also contained simultaneously persisting episomes of the Epstein-Barr virus. Most of the cell cultures except a pancreatic carcinoma line and foreskin fibroblasts did not produce infectious virus. These observations show that a herpesvirus genome can persist episomally in a broad range of cultured cell types. The variety of infectable cell types and species suggests the presence of a widely distributed and well conserved virus receptor for h. saimiri. Thus the h. saimiri genome could be applied more generally as a vector.

Blotting, Northern↗
PubMed1978

Herpesvirus ateles DNA and its homology with Herpesvirus saimiri nucleic acid.

Analysis of the structural organization of Herpesvirus ateles DNA shows that two types of viral DNA molecules are encapsidated in virions: (i) M-genomes, which contain 74% light sequences (L-DNA, 38% guanine plus cytosine) and 26% highly repetitive heavy sequences (H-DNA, 75% guanine plus cytosine), and (ii) defective H-genomes, which consist exclusively of repetitive H-DNA. The structure of M-genomes from H. ateles consists of an L-DNA region of about 70 x 10(6) daltons inserted between H-DNA termini of variable length. M-genomes with a shorter H-DNA region at one end of the molecule have a long stretch of H-DNA at the other end, resulting in a total molecular weight of 89.8 +/- 8.5 x 10(6). Thus it resembles the structure of M-genomes of H. saimiri. H-DNA of the two independent H. ateles isolates, strains 810 and 73, reveals different patterns after cleavage with restriction endonuclease Sma I. H-DNA of H. ateles 810 appears to consist of identical tandem repeat units with a molecular weight of 1,035,000; the H-DNA repeat unit of strain 73 is shorter (930,000 molecular weight). Corresponding DNA sequences of the two H. ateles strains (810 and 73) are completely homologous in cross-hybridizations. However, a discrete nucleotide sequence divergence between these virus strains is detected by measuring melting temperatures (T(m)) of DNA hybrid molecules. Some homology exists between H. ateles and H. saimiri DNA. Hybridization of L-DNA from H. ateles with L-DNA from H. saimiri shows about a 35% homology between the respective L-DNA sequences; the resulting heteroduplex molecules show a decrease of T(m) by 13.5 degrees C, corresponding to about a 9% mismatching in cross-hybridizing parts of L-regions. Very little homology is found between H-DNA of H. ateles and H. saimiri.

Base Sequence↗
PubMed1990

trans activation of the thymidylate synthase promoter of herpesvirus saimiri.

Herpesvirus saimiri has been shown to possess a thymidylate synthase (TS) gene that is unusual in its transcriptional regulation. Although TS is believed to be required for viral DNA synthesis, the TS-specific 2.5-kb mRNA was found most abundantly during the late phases of asynchronous virus replication in permissive cultures. To study the kinetics of gene activation, the TS promoter and regulatory sequences were cloned upstream of the chloramphenicol acetyltransferase (CAT) gene. No CAT expression or transcripts were found after transfection of fusion genes into permissive owl monkey kidney (OMK) cells. However, the promoter was strongly activated when CAT plasmids were cotransfected with intact herpesvirus saimiri virion DNA or were transferred to OMK cells that were lytically infected with herpesvirus saimiri or a related herpesvirus, herpesvirus ateles. CAT was expressed at reduced levels in cultures when viral DNA replication was inhibited by phosphonoacetic acid; this indicates that the gene is activated during the delayed-early phase. However, the highest amounts of mRNA were present in the late period of replication. Deletion analyses localized essential response elements for trans activation in the promoter upstream region between nucleotides -311 and -56; they consisted of related tandem repeats and perfect palindromes. A sequence with two overlapping palindromes of 16 and 18 bp was found to be a major target for activation of the herpesvirus saimiri TS promoter. These palindromes did not have any significant homologies with known sequences of herpesviruses or cellular DNA; the 18-bp palindrome had, however, a certain structural similarity with a conserved sequence of the E2-responsive cis sequence that is required for transcription regulation of early papillomavirus genes.

Animals↗