Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Copolymer-1 (COP-1) elicits neuroprotective activities in a wide range of neurodegenerative disorders. This occurs, in part, by adaptive immune-mediated suppression of microglial inflammatory responses. Because HIV infection and immune activation of perivascular macrophages and microglia drive a metabolic encephalopathy, we reasoned that COP-1 could be developed as an adjunctive therapy for disease. To test this, we developed a novel animal model system that reflects HIV-1 encephalitis in rodents with both innate and adaptive arms of the immune system. Bone marrow-derived macrophages were infected with HIV-1/vesicular stomatitis-pseudotyped virus and stereotactically injected into the basal ganglia of syngeneic mice. HIV-1 pseudotyped with vesicular stomatitis virus envelope-infected bone marrow-derived macrophages induced significant neuroinflammation, including astrogliosis and microglial activation with subsequent neuronal damage. Importantly, COP-1 immunization reduced astro- and microgliosis while diminishing neurodegeneration. Hippocampal neurogenesis was, in part, restored. This paralleled reductions in proinflammatory cytokines, including TNF-alpha and IL-1beta, and inducible NO synthase, and increases in brain-derived neurotrophic factor. Ingress of Foxp3- and IL-4-expressing lymphocytes into brains of COP-1-immunized animals was observed. We conclude that COP-1 may warrant therapeutic consideration for HIV-1-associated cognitive impairments.
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PMID:Copolymer-1 induces adaptive immune anti-inflammatory glial and neuroprotective responses in a murine model of HIV-1 encephalitis. 1787 29

Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus-induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV-1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus. Mechanisms for antiviral activity of Glycyrrhiza spp. include reduced transport to the membrane and sialylation of hepatitis B virus surface antigen, reduction of membrane fluidity leading to inhibition of fusion of the viral membrane of HIV-1 with the cell, induction of interferon gamma in T-cells, inhibition of phosphorylating enzymes in vesicular stomatitis virus infection and reduction of viral latency. Future research needs to explore the potency of compounds derived from licorice in prevention and treatment of influenza A virus pneumonia and as an adjuvant treatment in patients infected with HIV resistant to antiretroviral drugs.
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PMID:Antiviral effects of Glycyrrhiza species. 1788 24

Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45(high)CD11b(+)) and CD8(+) T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8(+) T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-gamma) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.
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PMID:Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system. 1926 38

HIV-1-associated neurocognitive impairments are intrinsically linked to microglial immune activation, persistent viral infection, and inflammation. In the era of antiretroviral therapy, more subtle cognitive impairments occur without adaptive immune compromise. We posit that adaptive immunity is neuroprotective, serving in both the elimination of infected cells through CD8(+) cytotoxic T cell activities and the regulation of neuroinflammatory responses of activated microglia. For the latter, little is known. Thus, we studied the neuromodulatory effects of CD4(+) regulatory T cells (Treg; CD4(+)CD25(+)) or effector T cells in HIV-1-associated neurodegeneration. A newly developed HIV-1 encephalitis mouse model was used wherein murine bone marrow-derived macrophages are infected with a full-length HIV-1(YU2)/vesicular stomatitis viral pseudotype and injected into basal ganglia of syngeneic immunocompetent mice. Adoptive transfer of CD3-activated Treg attenuated astrogliosis and microglia inflammation with concomitant neuroprotection. Moreover, Treg-mediated anti-inflammatory activities and neuroprotection were associated with up-regulation of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor expression and down-regulation of proinflammatory cytokines, oxidative stress, and viral replication. Effector T cells showed contrary effects. These results, taken together, demonstrate the importance of Treg in disease control and raise the possibility of their utility for therapeutic strategies.
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PMID:Neuromodulatory activities of CD4+CD25+ regulatory T cells in a murine model of HIV-1-associated neurodegeneration. 1926 65

A number of methods have been employed in attempts to induce encephalitis in guinea pigs with the Levaditi C strain of herpes virus. Some of these consisted of different modes of inoculation of the virus itself and others of different ways of combining it with vesicular stomatitis and neurovaccine viruses so as to obtain the concomitant effects of both. In still another test the Levaditi virus was combined with the neurovaccine in a manner calculated to bring about the maximum action of each at the same time. By all these methods, the Levaditi virus failed to evoke the characteristic encephalitis which this specimen is capable of inducing uniformly in rabbits. On the other hand, when the Levaditi herpes virus is inoculated into the brain of guinea pigs in conjunction with suitably timed corneal injections, it acquires active encephalitogenic properties. The results just noted suggest several considerations: 1. The possibility of increasing the virulence of a filtrable virus by animal passage in a special manner. It is not likely that the increase as observed was due to dosage, for after the virus acquired its encephalitogenic property for guinea pigs, the usual amounts of virus suspensions sufficed to induce, in a uniform way, typical encephalitis. 2. The opinion previously expressed by Flexner that the guinea pig serves merely to separate weak from strong strains of herpes virus is supported: for only according to the particular method described, could the encephalitogenic power of the Levaditi virus be developed and the weak be converted into a strong herpes strain. With the acquisition of this power, the Levaditi virus acted in precisely the same manner as strong herpes strains both in the guinea pig and the rabbit. Moreover, it was shown in guinea pigs that cross-immunity occurs between weak and strong strains. 3. The two samples of neurovaccine virus employed were incapable of inducing encephalitis in guinea pigs after intracutaneous, intratesticular, corneal, or intracerebral inoculation, although they were actively encephalitogenic in rabbits. In spite of the fact that the vaccine virus and herpes virus are different, as shown by the histopathology and absence of cross-immunity, they behave in the same way when injected into the brain of the guinea pig. The failure of the concomitant action of both viruses to induce encephalitis in the guinea pig suggests that the association of two viruses, under the experimental conditions outlined, is incapable of inducing encephalitis, if either, by itself, is non-encephalitogenic. 4. The serum from normal guinea pigs may neutralize a weak (Levaditi C) but not a strong (H.F.) strain of herpes virus; but the neutralizing action of the serum on Levaditi C virus is not uniform. 5. The Levaditi strain of virus can increase in quantity in the brain of the guinea pig to a degree which permits detection and yet fails to evoke any distinctive clinical picture or definite histopathological changes. 6. Repeated intraperitoneal injections of Levaditi virus in guinea pigs elicit no signs of infection, yet they induce a solid immunity to strong strains of herpes virus.
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PMID:THE ACTION OF THE LEVADITI STRAIN OF HERPES VIRUS, AND OF VACCINE VIRUS IN THE GUINEA PIG : SINGLE AND COMBINED EFFECTS. 1986 92

We have studied certain properties, additional to those previously described (3), of the virus of vesicular stomatitis of horses, and of the characteristic biological reactions of the virus of equine encephalomyelitis. It has been found that the virus of stomatitis, ordinarily dermotropic, can acquire neurotropism and the neurotropic encephalomyelitis virus can, in turn, be rendered dermotropic in its action. The neurotropism in both instances is associated with definite, although not pronounced, viscerotropism. Both viruses can bring about a similar infection in the white mouse, rat, guinea pig, rabbit, and rhesus or cynomolgus monkeys. Of these animals, rabbits show the lowest degree of susceptibility and mice the highest, especially after intracerebral inoculation. The mouse is the best animal for work with these viruses because of the uniform and rapidly lethal encephalitis which can be induced in it. Moreover, the mouse is highly sensitive to the instillation of the viruses in the nasal passages: 1 to 10 million dilution sufficing to induce a fatal encephalitis. The uninjured nasal mucosa of mice appears, therefore, to be as susceptible to experimental infection as the traumatized brain or pads of animals. The microscopic changes accompanying the reactions to both viruses reveal, in rapidly lethal infections, pronounced destructive lesions in the cells of the central nervous system. When the experimental disease is more protracted in its course, however, these lesions are associated with beginning productive, inflammatory reactions, consisting chiefly of mononuclear infiltrations. In the latter instances, characteristic, intranuclear inclusion bodies can be more readily observed. Both viruses can be cultivated with facility in the medium of minced chicken embryonic tissue suspended in Tyrode's solution, although 24 to 48 hour old chicks are refractory to artificial infection. No cross-immunity reactions occur between the two strains of stomatitis virus or between them and the encephalomyelitis strain. The viruses are evidently similar in many biological properties. In view of the fact that the horse is the natural host for both, it is suggested that they may be generically related. They are not, of course, identical since cross-immunity between them does not exist. The absence of cross-immunity does not, however, exclude the possibility of a generic relationship, for there are at least three immunologically distinct types of foot-and-mouth disease, two of vesicular stomatitis, and two of equine encephalomyelitis (14) virus.
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PMID:COMPARATIVE STUDIES ON THE VIRUSES OF VESICULAR STOMATITIS AND EQUINE ENCEPHALOMYELITIS (1). 1987 Feb 37

1. Injection of vesicular stomatitis virus into the leg muscles of young mice gives rise to flaccid paralysis of the inoculated extremity as the first clinical sign of a disease which is invariably fatal; old mice similarly injected with the largest doses of virus survive without exhibiting any signs of illness. 2. In young mice the virus was shown to multiply at the site of inoculation and to invade the sciatic nerve and spinal cord; there was no evidence of multiplication of virus in the blood or viscera. 3. In old mice, after intramuscular injection of as much as 10 million M.C.L.D., there was no evidence of either local or systemic multiplication; in spite of the persistence of thousands of M.C.L.D. of virus at the site of inoculation for at least 4 days, there was no detectable invasion of the sciatic nerve or the central nervous system. 4. Injection of the virus directly into the sciatic nerve of old mice led to the typical paralytic disease in half the number of animals. 5. For 3 days after intrasciatic injection the virus could be demonstrated in the nerve but not in the spinal cord or brain. At the onset of paralysis (6th day) virus was detectable in the spinal cord but no longer in the inoculated nerve. 6. The capacity of the virus to invade the central nervous system from the nerve but not from the muscle suggested the existence of a barrier in the muscle or myoneural junction. 7. Injection of the virus into the vitreous humor of the eye is followed by a fatal encephalitis in 15 day old mice, but 1 year old mice, with few exceptions, survive without showing signs of disease. 8. The spread of virus in the brains of intraocularly injected, 15 day old mice was too rapid to indicate the pathways which were pursued, but in 21 day old mice there was evidence that the primary pathway was probably along the axons of the optic nerve with decussation to the contralateral diencephalon and mesencephalon, and subsequent early spread to the corresponding occipital cortex. In resistant, old mice, however, no virus was found in any part of the brain.
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PMID:INFLUENCE OF HOST FACTORS ON NEUROINVASIVENESS OF VESICULAR STOMATITIS VIRUS : II. EFFECT OF AGE ON THE INVASION OF THE PERIPHERAL AND CENTRAL NERVOUS SYSTEMS BY VIRUS INJECTED INTO THE LEG MUSCLES OR THE EYE. 1987 Jun 48

Peripheral inoculation of vesicular stomatitis virus is constantly followed by myelitis or encephalitis in young mice, but not in young (or old) guinea pigs. The cause of this variation was elucidated by investigating the fate of the virus after inoculation by a number of different routes. Direct intracerebral injection of minimally infective amounts of virus was found to be equally fatal for young mice and young guinea pigs, indicating that the central nervous system as a whole was as easily injured by the virus in one species as in the other. The events following nasal instillation of the virus varied in young and old guinea pigs. While there appeared to be a transitory multiplication of virus in the nasal mucosa of both young and old, the central nervous system was regularly invaded only in the young. In these, virus was first found only in the anterior rhinencephalon; later it spread to the piriform and hippocampal (olfactory regions) but not to the neopallial portions of the cortex, and the only other area to exhibit virus was the diencephalon (including the pars optica hypothalami), where its further progression was apparently arrested. Absence of central nervous system disease following inoculation into sites supplied by spinal nerves (e.g. sciatic) was found to be due to inability of the virus to invade the nerves. Since direct intrasciatic inoculation frequently led to a fatal ascending myelitis, it was evident that the central nervous system could be invaded along the spinal nerves, and that they did not constitute the main barrier. Furthermore, since multiplication of virus was demonstrated in tissues supplied by the spinal nerves, a process of elimination made it seem possible that the specialized, terminal nerve endings might be the structures which prevent the progression of the virus from the infected tissues to the axons and hence also to the central nervous system. 7 day old guinea pigs (or guinea pigs as a species) were thus found to possess much the same type of barriers to the progression of peripherally inoculated vesicular stomatitis virus as are acquired by mice at a considerably later age. In a discussion of the present data, they have been correlated with known variations in neuroinvasiveness of other viruses and their bearing on the nature of inapparent or subclinical infections of the central nervous system has been considered.
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PMID:INFLUENCE OF HOST FACTORS ON NEUROINVASIVENESS OF VESICULAR STOMATITIS VIRUS : IV. VARIATIONS IN NEUROINVASIVENESS IN DIFIERENT SPECIES. 1987 Jul 16

The infection of cats by the virus of infectious feline agranulocytosis is followed by the production of specific neutralizing and protective antibodies, and recovery from the disease is associated with the development of solid immunity to reinfection. From the evidence presented it is obvious that the virus is not related to the viruses of hog cholera, lymphocytic choriomeningitis, fox encephalitis, vesicular stomatitis, the Western type of equine encephalomyelitis, herpes, and B virus infection.
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PMID:THE VIRUS OF INFECTIOUS FELINE AGRANULOCYTOSIS : II. IMMUNOLOGICAL RELATION TO OTHER VIRUSES. 1987 Dec 64

Chandipura virus (CHPV) is an emerging human pathogen associated with acute encephalitis and is related closely to vesicular stomatitis virus (VSV), a prototype rhabdovirus. Here, we demonstrate that the RNA polymerase L protein of CHPV exhibits a VSV-like RNA:GDP polyribonucleotidyltransferase (PRNTase) activity, which transfers the 5'-monophosphorylated (p-) viral mRNA start sequence to GDP to produce a capped RNA, and that the conserved HR motif in the CHPV L protein is essential for the PRNTase activity. Interestingly, the CHPV L protein was found to form two distinct SDS-resistant complexes with the CHPV mRNA and leader RNA start sequences; mutations in the HR motif significantly reduced the formation of the former complex (a putative covalent enzyme-pRNA intermediate in the PRNTase reaction), but not the latter complex. These results suggest that the rhabdoviral L proteins universally use the active-site HR motif for the PRNTase reaction at the step of the enzyme-pRNA intermediate formation.
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PMID:The HR motif in the RNA-dependent RNA polymerase L protein of Chandipura virus is required for unconventional mRNA-capping activity. 2010 17


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