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At least 1,387 records · Page 77Linked to original sources
PubMed1996

Endogenous D-type (HERV-K) related sequences are packaged into retroviral particles in the placenta and possess open reading frames for reverse transcriptase.

All primates studied to date produce retroviral-like particles in their placentae. We have purified these particles from two primate species, one Old World (human) and one New World (marmoset), and have identified the retroviral sequences which are packaged into these particles. Three families of sequences have been detected in these particles in human, all of which have the highest homology to B- and D-type retroviruses and to the human endogenous retrovirus HERV-K10. Previous studies have reported that the New World monkeys do not possess sequences with homology to HERV-K10. We have identified a new family of low-copy-number sequences which are present in New World monkeys and which possess 70% homology to the HERV-K family. Particles from both species possess reverse transcriptase activity and we have found that some of these retroviral particles package sequences which encode long open reading frames in pol, as revealed by expression cloning in Escherichia coli. These open reading frames could encode the reverse transcriptase enzyme activity found in the particles.

Animals↗
PubMed1997

Comparative analyses of LTRs of the ERV-H family of primate-specific retrovirus-like elements isolated from marmoset, African green monkey, and man.

We have isolated 8 different long terminal repeat (LTR) sequences of the ERV-H family of endogenous retrovirus-like elements from human chromosome 18, 9 from African green monkey, and 28 from marmoset. Human ERV-H LTRs have been divided into three types designated Type I, Type Ia, and Type II. Comparative analyses of the 45 isolated LTRs and 60 human ERV-H LTRs enabled a further subdivision into 13 subtypes. Type I elements were widely distributed in all three species. Their average evolutionary age (40 MYr), estimated by a consensus sequence approach, suggests that they first expanded in the genomes at the time New- and Old World monkeys diverged. The occurence of some very old Type I sequences indicate that ERV-H elements may have integrated even before prosimians and primates diverged. Type Ia and - II elements were found in both monkey species. Promoter active Type I and Type Ia LTRs were found while Type II LTRs were inactive. Promoter active Type I LTRs generally contained a functional GC/GT box immediately 3' to the TATA box, providing strong binding of Sp1 family proteins, while the highly promoter active Type Ia element H6 contained synergistically acting Sp1 binding sites located in the U3 enhancer region.

Animals↗
PubMed1997

Early detection of the lytic LMP-1 protein in EBV-infected B-cells suggests its presence in the virion.

The Epstein-Barr virus (EBV)-positive B958 cell line expresses two related membrane proteins encoded by BNLF-1 open reading frames. One protein (LMP-1) has been shown to be essential for the growth transforming properties of EBV. The second protein (the lytic LMP-1) is an amino-terminally truncated form of LMP-1 whose expression is associated with induction of EBV's lytic cycle. We have investigated the expression of full-length and lytic forms of LMP-1 immediately after infection of the EBV-negative, B-lymphoma cell line BJAB. Only the lytic LMP-1 protein is present in BJAB cells early (within minutes following addition of virus) after infection with virus derived from either uninduced or tetradecanoyl phorbol acetate and sodium butyrate-induced B958 cells. Lytic LMP-1 protein levels begin to decline by 48 hr after infection, whereas levels of full-length LMP-1 increase between 24 and 48 hr after infection and then remain constant. The presence of the lytic LMP-1 protein in infected cells is independent of both protein synthesis and virus internalization. We also find the lytic LMP-1 protein in BJAB cells early after infection (within 3 hr of addition of virus) with the HH514 strain of EBV, and HH514 cells treated with tetradecanoyl phorbol acetate and sodium butyrate, express high levels of both the lytic LMP-1 and full-length LMP-1 proteins. The lytic LMP-1 protein is enriched in purified virion preparations, and immunoelectron microscopic analysis indicates that EBV virions can be specifically labeled with anti-LMP-1 antisera. Together, these results are consistent with a model in which the lytic LMP-1 protein is present in the EBV virion and is carried into the B-cell upon infection and suggest a role for this protein in early infection events and/or in EBV's lytic cycle.

Animals↗
PubMed1997

Epstein-Barr virus induces GM-CSF synthesis by monocytes: effect on EBV-induced IL-1 and IL-1 receptor antagonist production in neutrophils.

Neutrophils play an important role in the control of viral infections by releasing a variety of potent agents. We previously demonstrated that Epstein-Barr virus (EBV) binds to human neutrophils and stimulates cytokine synthesis including interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1Ra). Since neutrophil functions are known to be modulated by the priming effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), we therefore investigated the cellular source of GM-CSF synthesis following treatment of leukocytes with EBV and the effect of GM-CSF on the production of IL-1, IL-1Ra, and superoxide by EBV-treated neutrophils. In enriched-cell populations, only monocytes were found to produce GM-CSF in response to EBV, which was maximal after 12 h of incubation. The results obtained with UV-irradiated particles or EBV neutralized with monoclonal antibody 72A1 suggest that contact between the cell and the gp350 of the viral envelope is sufficient to induce the release of GM-CSF. On the other hand, GM-CSF differentially upregulated EBV-induced IL-1 and IL-1Ra production by neutrophils. Pretreatment of neutrophils with GM-CSF prior to EBV activation synergistically enhanced the production of IL-1 alpha and IL-1 beta, but only marginally affected IL-1Ra synthesis. In addition, GM-CSF was also found to synergistically enhance the superoxide production by neutrophils in response to EBV. Molecular analysis showed that GM-CSF did not alter the IL-1 beta and IL-1Ra mRNA synthesis induced by EBV, suggesting that GM-CSF could act at a posttranslational level. Local production of GM-CSF by monocytes in tissues invaded by EBV could serve to potentiate the host defense mechanisms directed toward the destruction of the infectious virus.

Animals↗
PubMed1999

Nitric oxide down-regulates Epstein-Barr virus reactivation in epithelial cell lines.

Nitric oxide (NO), a mediator of biological functions, has an antimicrobial activity against a variety of pathogens including viruses. In this study, we found that a constitutive, low level of inducible NO synthase (iNOS) mRNA was expressed in the EBV-infected gastric tissue-derived GT38 and GT39 cell lines, by analysis with the reverse transcription-polymerase chain reaction (RT-PCR) and Southern blotting. Treatment of these cells with a specific NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA), induced the immediate-early, EBV transactivator gene BZLF1 protein ZEBRA, suggesting a significant increase in EBV reactivation by L-NMMA. Northern blotting demonstrated that BZLF1 and BRLF1 transcripts were also induced by 12-O-tetradecanoylphorbol-13 acetate (TPA). Meanwhile, constitutive expression of iNOS mRNA was inhibited by TPA. L-NMMA also enhanced TPA-induced expression of the BZLF1 gene. On the other hand, a NO donor, S-nitroso-N-acetylpenicillamine (SNAP), which releases NO in an aqueous solution, inhibited the TPA-induced BZLF1 gene expression in a dose-dependent manner at both mRNA and protein levels. These results demonstrated that NO is a regulatory factor in maintaining virus latency via inhibiting EBV reactivation in the infected epithelial cells.

Animals↗
PubMed1999

Tyrosines 60, 64, and 101 of Epstein-Barr virus LMP2A are not essential for blocking B cell signal transduction.

Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is expressed on the membrane of B-lymphocytes and blocks B cell receptor (BCR) signaling in EBV-transformed B-lymphocytes in vitro. The LMP2A amino-terminal domain, which is essential for the LMP2A-mediated block of B cell signal transduction, contains eight tyrosine residues. Three of these tyrosine residues (Y74, Y85, and Y112) have been demonstrated to be essential for the LMP2A-mediated block on protein tyrosine phosphorylation, calcium mobilization, and induction of BZLF1 expression after BCR activation. To investigate the importance of tyrosines at positions 60, 64, and 101 on B cell signaling, EBV recombinants were constructed containing a tyrosine-to-phenylalanine point mutation at amino acid 60, 64, or 101 within LMP2A. Tyrosine phosphorylation, calcium mobilization, and induction of BZLF1 expression were not affected by any of the tyrosine point mutations after BCR activation. In addition, constitutive phosphorylation of LMP2A was unaffected by any of the tyrosine point mutations. These data indicate that tyrosines 60, 64, and 101 are not essential for the LMP2A-mediated block of B cell signal transduction in transformed cell lines.

Amino Acid Sequence↗
PubMed2000

Herpesvirus saimiri pathogenicity enhanced by thymidine kinase of herpes simplex virus.

Herpesvirus saimiri can be used as an efficient gene expression vector for human T lymphocytes and thus may allow applications in experimental leukemia therapy. We constructed recombinant viruses for the functional expression of the thymidine kinase (TK) of herpes simplex virus type 1 (HSV) as a suicide gene. These viruses reliably allowed the targeted elimination of transduced nonpermissive human T cells in vitro after the administration of ganciclovir. To test the reliability of this function under the most stringent permissive conditions, in this study we analyzed the influence of the prodrugs ganciclovir and acyclovir in common marmosets on the acute leukemogenesis induced by either wild-type herpesvirus saimiri C488 or by a recombinant derivative expressing TK of HSV. Antiviral drug treatment did not influence the rapid development of acute disease. In contrast, the presence of the HSV tk gene resulted in a faster disease progression. In addition, HSV TK-expressing viruses showed faster replication than wild-type virus in culture at low serum concentrations. Thus, HSV TK accelerates the replication of herpesvirus saimiri and enhances its pathogenicity. This should be generally considered when HSV TK is applied as a transgene in replication-competent DNA virus vectors for gene therapy.

Acyclovir↗
PubMed1998

Chronic TVP-1012 (rasagiline) dose--activity response of monoamine oxidases A and B in the brain of the common marmoset.

The stereospecific form of the known acetylenic mechanism-based MAO-inhibitor AGN1135 (Rasagiline, TVP-1012) is devoid of sympathomimetic amphetamine-like properties. To evaluate the efficiency and selectivity of subcutaneous injections of TVP-1012 (dose range from 0.01 up to 10 mg/kg for 7 days) the activities of monoamine oxidases A and B (MAO-A,-B) were determined in different brain regions of the common marmoset. At a dose of 0.1 mg/kg TVP-1012, almost 80% of MAO-B activity is inhibited in all brain regions investigated (prefrontal and occipital cortex, cerebellum, caudate nucleus, putamen, nucleus accumbens). In contrast, MAO-A is not inhibited in putamen and nucleus accumbens. However, by increasing the TVP-1012 dose to 0.5 mg/kg, MAO-A is inhibited to a significant extent as well, concomitant to total inhibition of MAO-B. The results obtained indicate that TVP-1012 irreversibly inhibits both types of MAO in the common marmoset with selectivity for MAO-B at doses less than 0.5 mg/kg. TVP-1012 could be useful in studies requiring selective MAO-B inhibition without concomitant sympathomimetic amphetamine-like effects and could thus be of therapeutic interest for Parkinson's disease and retarded depression.

Animals↗
PubMed1994

In vivo transfection by hepatitis A virus synthetic RNA.

Marmosets injected intrahepatically with nucleic acids (cDNA and RNA transcripts) representing the full-length genome of the wild-type HM-175 strain of hepatitis A virus experienced acute hepatitis and seroconversion to hepatitis A virus capsid proteins. The hepatitis was comparable in severity to that caused by infection with the wild-type virus. The viral cDNA and the hepatitis A virus recovered from the feces of an injected animal contained the same marker mutation. Therefore, intermediate cell culture steps can be omitted and the virulence of a hepatitis A virus encoded by a cDNA clone can be evaluated by direct transfection of marmosets.

Animals↗
PubMed1994

Molecular evolution of interleukin-3.

Chimpanzee, tamarin, and marmoset interleukin-3 (IL-3) genes were cloned, sequenced, and expressed. Western blot analysis demonstrated that functional genes were isolated. IL-3 sequences were compared with those of mouse, rat, rhesus monkey, gibbon, and man. Multiple alignment of the IL-3 coding regions showed that only a few regions had been conserved during mammalian evolution, which are likely associated with functional domains of the IL-3 protein. Substitution rates for the various lineages were calculated and the numbers of synonymous and nonsynonymous substitutions were estimated separately. Distance matrices of the IL-3 coding regions were used to construct phylogenetic trees which revealed large differences in IL-3 evolution rate as well as a more rapid substitution rate for rodents and a rate slowdown during hominoid evolution. Extremes were rhesus monkey IL-3, which accumulated few synonymous substitutions, and gibbon IL-3, which had almost exclusively synonymous substitutions. In rhesus monkey IL-3, nonsynonymous substitutions outnumbered synonymous substitutions, which could not be readily explained by a random process of substitutions. We assume that during evolution of IL-3, the majority of the amino acid replacements and the impaired interspecies functional cross-reactivity originate from selection mechanisms with the most likely selective force being the structure of the heterodimeric IL.3 cell-surface receptor. Insight into IL-3 architecture and structural analysis of the IL-3 receptor are needed to analyze the unusually fast evolution of IL-3 in more detail.

Animals↗
PubMed1993

The competitive NMDA antagonist CPP protects substantia nigra neurons from MPTP-induced degeneration in primates.

Degeneration of nigrostriatal dopaminergic neurons is the primary histopathological feature of Parkinson's disease. The neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces a neurological syndrome in man and non-human primates very similar to idiopathic Parkinson's disease by selectively destroying dopaminergic nigrostriatal neurons. This gives rise to the hypothesis that Parkinson's disease may be caused by endogenous or environmental toxins. Endogenous excitatory amino acids (EAAs) such as L-glutamate could be involved in neurodegenerative disorders including Parkinson's disease. We report in this study that the competitive NMDA antagonist CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) protects nigral tyrosine hydroxylase (TH) positive neurons from degeneration induced by systemic treatment with MPTP in common marmosets. This indicates that EAAs are involved in the pathophysiological cascade of MPTP-induced neuronal cell death and that EAA antagonists may offer a neuroprotective therapy for Parkinson's disease.

Animals↗
PubMed1993

Anorectic effect and brain concentrations of D-fenfluramine in the marmoset: relationship to the in vivo and in vitro effects on serotonergic mechanisms.

The present study investigated the anorectic activity of d-fenfluramine (d-F) and the relationship with brain levels of unchanged drug and its metabolite d-norfenfluramine (d-NF) in marmosets, relating them to neurochemical effects on the serotoninergic system. d-F and d-NF were equally active in reducing food intake (ED50 about 3 mg/kg, p.o.). However, the brain concentrations of the metabolite required to reduce food intake after synthetic d-NF were more than twice those after d-F, indicating that d-NF contributes to but does not completely explain the anorectic effect of d-F. At this dose d-F did not appreciably modify the serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) contents of the brain regions examined, except for a slight enhancement of 5-HIAA in hippocampus. In vitro in brain cortical synaptosomes d-F inhibited [3H]5-HT uptake more potently than d-NF, as in other species. d-F and d-NF showed similar potency in stimulating [3H]5-HT release, in a Ca++ dependent manner. The tritium released by d-F and d-NF appeared to be mainly unmetabolized [3H]5-HT. Like in other species the marmoset too has saturable and specific [3H]d-F binding sites, for which d-NF has lower affinity. d-F and d-NF have low affinities for 5-HT receptor subtypes, except that d-NF has appreciable affinity for 5-HT1C and 5-HT1D receptors. Unlike in rodents but similarly to primates in the striatum the pharmacology of 5-HT receptors seems to correspond to the 5-HT1D subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

RPR 101821, a new potent cholesterol-lowering agent: inhibition of squalene synthase and 7-dehydrocholesterol reductase.

RPR 101821 (trans-2-[4-(benzoxazol-2-yl)-phenylmethoxy] amino cyclohexane hydrochloride) is a potent cholesterol-lowering agent in rodents and marmoset. The compound inhibited rat liver microsomal squalene synthase (IC50 = 1 nM) and 7-dehydrocholesterol (7DHC) reductase (IC50 = 1 microM; Lewis et al. 1995). When RPR 101821 (10 mg/kg), the 7DHC reductase inhibitor BM 15.766 (4[2-[4-(4-chlorocinnamyl)piperazine-1-yl]ethyl] benzoic acid; 10 mg/kg) or the HMG-CoA reductase inhibitor lovastatin (30 mg/kg) was given orally to rats at -29 h, -21 h and -5 h, serum cholesterol was reduced by 56%, 46% or 15%, respectively. The reduction in cholesterol with RPR 101821 was associated with an accumulation of 7DHC in serum, suggesting an inhibition of 7DHC reductase. In the presence of BM 15.766, RPR 101821 reduced the serum accumulation of 7DHC in a dose-dependent manner, with complete inhibition at 30 mg/kg, p.o. In Balb-cJ mice, RPR 101821 and lovastatin (50 mg/kg, b.i.d., p.o., for 14 days) lowered serum cholesterol by 67% and 2%, respectively. In marmosets, RPR 101821 and lovastatin (both at a dose of 10 mg/kg, p.o., b.i.d., for 7 days) reduced cholesterol by 28% and 19%, respectively. In summary, RPR 101821 is an orally effective potent cholesterol-lowering agent in rodents and a small primate species. The suggested mechanism of hypocholesterolemic effect is the inhibition of squalene synthase and 7DHC reductase.

Animals↗
PubMed1988

Ultrastructure of the meninges at the site of penetration of veins through the dura mater, with particular reference to Pacchionian granulations. Investigations in the rat and two species of New-World monkeys (Cebus apella, Callitrix jacchus).

At the sites where a vein penetrates through the dura mater, two aspects deserve particular attention: (i) The delineation of the perivascular cleft, a space belonging to the interstitial cerebrospinal fluid (CSF) compartment, toward the interior hemal milieu of the dura mater. (ii) The relationship between the perivascular arachnoid layer and the subdural neurothelium at the point of vascular penetration. These problems were investigated in the rat and in two species of New-World monkeys (Cebus apella, Callitrix jacchus). Concerning the first aspect, tight appositions of meningeal cells to the vessel wall, the basal lamina of which is widened and enriched with microfibrils, prevent communication between the interstitial CSF in the perivascular cleft and the hemal milieu in the dura mater. With reference to the second aspect, the perivascular arachnoid cells are transformed into neurothelial cells at the point where they become exposed to the hemal milieu of the dura mater and subsequently continuous with the subdural neurothelium. Leptomeningeal protrusions encompassing outer CSF space can penetrate into the dura mater. These protrusions may expand and branch repeatedly, forming along the wall of the dural sinus Pacchionian granulations. At these sites, however, the structural integrity of the sinus wall and the Pacchionian granulation is not lost. Numerous vesiculations not only in the sinus and vascular walls, but also in the cellular arrays of the Pacchionian granulations or paravascular leptomeningeal protrusions indicate mechanisms of transcellular fluid transport. Moreover, the texture of the leptomeningeal protrusions favors an additional function of these structures as a "volume" buffer.

Animals↗
PubMed1993

Distribution of cytochrome oxidase in layers IV and V of the striate cortex in neonate monkeys.

The uniformly dense staining for cytochrome oxidase (CO) in layer IV of area 17 in adult monkeys has been described as developing from a bilaminar pattern in neonates being composed of a broad CO band in layer IV alpha and a narrow CO band attributed to the innermost zone of layer IV beta. Here we present evidence, in the neonate marmoset monkey, for the narrow CO band to be localized in the outermost rim of layer V, designated as sublayer Va.

Aging↗
PubMed1991

Topographical mapping of the thalamocortical projections in rodents and comparison with that in primates.

The general topographical organization of the thalamo-cortical projection of two rodents, the Siberian hamster (Phodopus sungorus) and the Guinea pig (Cavia aperta) was investigated with the HRP-method and compared with that of the new world primate marmoset (Cal-lithrix jacchus) as shown in a companion study by Brysch et al. (1990). HRP was injected into various regions of the cortex in different animals and hemispheres, and plots were made of the retrogradely stained thalamic projection neurons. The thalamocortical projection is virtually identical in both rodent species. It is topological throughout in that nearby cortical injections label nearby, though overlapping cell groups in the thalamus. Cortical injections in a rostro-caudal progression labelled thalamic projection zones on top of each other, layered like tiles on a roof or fish scales, beginning in the rostromedial and ending in the caudo-dorsal thalamus. The progression vector of thalamic zones projecting successively from more rostral to more caudal cortical zones is twisted and turns from a predominantly mediolateral direction in the anterior thalamus to an essentially ventro-dorsal direction in the posterior thalamus In the marmoset, the thalamo-cortical topography follows the same topological rule, with the exception of the lateral geniculate body which is translocated latero-ventrally and separated from the rest of the thalamus as in all primates. This suggests a general thalamo-cortical mapping rule common to all mammals which can be related to gradients and timing of cell birth in the thalamus. It is proposed that this mapping rule is the consequence of successive appositions of neurons in the medio-ventral thalamus during ontogenetic development.

Animals↗
PubMed1995

A comparison of the behavioural effects of embryonic nigral grafts in the caudate nucleus and in the putamen of marmosets with unilateral 6-OHDA lesions.

The behaviour of marmosets with unilateral 6-hydroxydopamine lesions of the nigrostriatal bundle and grafts of embryonic mesencephalon in either the caudate nucleus or the putamen was compared with that of lesion-alone and unoperated controls. The grafts comprised injections of cell suspensions prepared from marmoset ventral mesencephalon (i.e. allografts) targeted at four sites either entirely within the caudate nucleus or entirely within the putamen. Behavioural tests, including measures of amphetamine-induced rotation, neglect and use of each arm to retrieve food from inside tubes, were given before and after the 6-hydroxydopamine lesion and at regular intervals for 6 months after transplantation surgery. Grafts in the caudate nucleus reduced the ipsilateral rotation induced by amphetamine, whereas grafts in the putamen did not. Despite the absence of an effect on rotation, the putamen grafts were effective in reducing lesion-induced deficits on the task in which the marmosets were required to reach into tubes. In this latter task, the caudate grafts were also effective when the monkeys were given a free choice of which hand to use. However, when constrained to use the hand contralateral to the lesion and graft, the performance of the marmosets with caudate grafts was not significantly improved compared with that of lesion-alone controls. Neither the grafts in the caudate nucleus nor the grafts in the putamen abolished the contralateral somatosensory neglect induced by the lesion, although there was a trend for the marmosets with putamen grafts to contact the label on the contralateral side more quickly than those with caudate grafts or the lesion-alone controls. These results demonstrate that the location of embryonic nigral grafts within the primate striatum influences the profile of functional recovery.

Animals↗