Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Limitin has sequence homology with alpha interferon (IFN-alpha) and IFN-beta and utilizes the IFN-alpha/beta receptor. However, it has no influence on the proliferation of normal myeloid and erythroid progenitors. In this study, we show that limitin has antiviral activity in vitro as well as in vivo. Limitin inhibited not only cytopathic effects in encephalomyocarditis virus- or herpes simplex virus (HSV) type 1-infected L929 cells, but also plaque formation in mouse hepatitis virus (MHV) type 2-infected DBT cells. In addition, administration of limitin to mice suppressed MHV-induced hepatitis and HSV-induced death. The antiviral activity may be mediated in part by 2',5'-oligoadenylate synthetase, RNA-dependent protein kinase, and Mx protein, which inhibit viral replication or degrade viral components, because limitin induced their mRNA expression and enzyme activity. While limitin has antiviral activity as strong as that of IFN-alpha in vitro (the concentration that provided 50% inhibition of cytopathic effect is approximately 30 pg/ml), IFN regulatory factor 1 (IRF-1) dependencies for induction of an antiviral state were different for limitin and IFN-alpha. In IRF-1-deficient fibroblasts, a higher concentration of limitin than of IFN-alpha was required for the induction of antiviral activity and the transcription of proteins from IFN-stimulated response element. The unique signals and the fewer properties of myelosuppression suggest that a human homolog of limitin may be used as a new antiviral drug.
 ...
PMID:Antiviral activity of limitin against encephalomyocarditis virus, herpes simplex virus, and mouse hepatitis virus: diverse requirements by limitin and alpha interferon for interferon regulatory factor 1. 1291 74

To demonstrate the anti-cytomegalovirus (CMV) activity of allitridin injection (AI), an active anti-infection component of garlic, the in vitro effects of AI on human CMV (HCMV) AD169 and 7 newly isolated strains from patients and its in vivo effect on mice of murine CMV (MCMV) hepatitis were assessed. It was found that plaque reduction rate reached 63.5% after infected cells were treated with cell maximal tolerable concentration (7.5 micrograms/ml) of AI. Meanwhile, flow cytometric analysis for effect of AI on expression of HCMV immediate-early antigen (IEA) showed that IEA inhibition rate of 7 isolated strains was in the range from 43.3% to 66.7%, with a mean of 58.4%, similar to that of AD169 strain (60.5%). On the other hand, in vivo anti-CMV activity of AI was evaluated in terms of liver pathological changes, liver function and viral replication. Six model mice with MCMV hepatitis received the treatment of AI for 2 weeks. The severity of liver damage, levels of sALT and MCMV IE genes expression in liver tissues in the treated mice were significantly lower than those of the corresponding untreated controls. Our results showed that AI had an obvious anti-CMV activity both in vitro and in vivo.
 ...
PMID:Treatment of hepatitis caused by cytomegalovirus with allitridin injection--an experimental study. 1293 15

Previous reports have documented that cholesterol supplementations increase cytopathic effects in tissue culture and also intensify in vivo pathogenicities during infection by the enveloped coronavirus murine hepatitis virus (MHV). To move toward a mechanistic understanding of these phenomena, we used growth media enriched with methyl-beta-cyclodextrin or cholesterol to reduce or elevate cellular membrane sterols, respectively. Cholesterol depletions reduced plaque development 2- to 20-fold, depending on the infecting MHV strain, while supplementations increased susceptibility 2- to 10-fold. These various cholesterol levels had no effect on the binding of viral spike (S) proteins to cellular carcinoembryonic antigen-related cell adhesion molecule (CEACAM) receptors, rather they correlated directly with S-protein-mediated membrane fusion activities. We considered whether cholesterol was indirectly involved in membrane fusion by condensing CEACAMs into "lipid raft" membrane microdomains, thereby creating opportunities for simultaneous binding of multiple S proteins that subsequently cooperate in the receptor-triggered membrane fusion process. However, the vast majority of CEACAMs were solubilized by cold Triton X-100 (TX-100), indicating their absence from lipid rafts. Furthermore, engineered CEACAMs appended to glycosylphosphatidylinositol anchors partitioned with TX-100-resistant lipid rafts, but cells bearing these raft-associated CEACAMs were not hypersensitive to MHV infection. These findings argued against the importance of cholesterol-dependent CEACAM localizations into membrane microdomains for MHV entry, instead suggesting that cholesterol had a more direct role. Indeed, we found that cholesterol was required even for those rare S-mediated fusions taking place in the absence of CEACAMs. We conclude that cholesterol is an essential membrane fusion cofactor that can act with or without CEACAMs to promote MHV entry.
 ...
PMID:Requirements for CEACAMs and cholesterol during murine coronavirus cell entry. 1499 Jun 88

Adenoviruses are responsible for a broad range of clinical diseases that may be associated with high mortality, including pneumonia, hepatitis, encephalitis, hemorrhagic cystitis, nephritis, and gastroenteritis in immunocompromised patients, including HIV-infected individuals. Here we report the identification of halo-substituted stavudine phenyl phosphoramidate derivatives as a new class of dual-function anti-HIV agents with potent and selective anti-adenovirus (ADV) activity. We examined the investigational stavudine phenyl phosphoramidate derivative stampidine and 12 structurally similar stavudine derivatives for anti-ADV activity. All 13 derivatives of stavudine, including stampidine, were substantially more potent than stavudine and inhibited ADV-induced plaque formation at nanomolar IC(50) values. Compounds with halo substitutions in the phenyl ring as well as the unsubstituted compound 607 were more potent than compounds with methoxy, methyl, or cyano substitutions. Compound 113 (stampidine) with a 4-Br substitution and compound 609 with a 4-Cl substitution were identified as the most potent lead anti-ADV agents. Compound 113/Stampidine inhibited ADV-induced plaque formation in skin fibroblasts in a concentration-dependent fashion with a mean (+/-S.E.M.) IC(50) value of 17 +/- 2 nM without any evidence of cytotoxicity even at 100 microM. Similarly, compound 609 inhibited ADV-induced plaque formation with an IC(50) value of 27 +/- 3 nM. We next sought to determine if the lead compounds 113 and 609 can also inhibit other viruses. Both compounds exhibited potent anti-HIV activity at nanomolar concentrations. However, neither compound exhibited any antiviral activity against non-HIV viruses, including Cytomegalovirus (CMV), Type I or Type II herpes simplex viruses (HSV-1, HSV-2), enterovirus ECHO 30, or respiratory syncytial virus (RSV) (IC(50) > 100 microM). The remarkable anti-ADV potency of the lead compounds stampidine and compound 609 warrants the further development of these promising new antiviral agents for possible clinical use in ADV infected patients.
 ...
PMID:Phenyl phosphoramidate derivatives of stavudine as anti-HIV agents with potent and selective in-vitro antiviral activity against adenovirus. 1505 Nov 70

In September and October 2002, an epizootic of neurologic disease occurred at an alligator farm in Florida (USA). Three affected American alligators (Alligator mississippiensis) were euthanatized and necropsied, and results confirmed infection with West Nile virus (WNV). The most significant microscopic lesions were a moderate heterophilic to lymphoplasmacytic meningoencephalomyelitis, necrotizing hepatitis and splenitis, pancreatic necrosis, myocardial degeneration with necrosis, mild interstitial pneumonia, heterophilic necrotizing stomatitis, and glossitis. Immunohistochemistry identified WNV antigen, with the most intense staining in liver, pancreas, spleen, and brain. Virus isolation and RNA detection by reverse transcription-polymerase chain reaction confirmed WNV infection in plasma and tissue samples. Of the tissues, liver had the highest viral loads (maximum 10(8.9) plaque-forming units [PFU]/0.5 cm3), whereas brain and spinal cord had the lowest viral loads (maximum 10(6.6) PFU/0.5 cm3 each). Virus titers in plasma ranged from 10(3.6) to 10(6.5) PFU/ml, exceeding the threshold needed to infect Culex quinquefasciatus mosquitoes (10(5) PFU/ml). Thus, alligators may serve as a vertebrate amplifying host for WNV.
 ...
PMID:West Nile virus infection in farmed American alligators (Alligator mississippiensis) in Florida. 1582 15

A plaque assay for duck plague virus was developed for a chicken embryo-adapted virus and a duck lethal virus and used to determine the identity of these viruses. Using the plaque inhibition neutralization test, duck plague virus was differentiated from Newcastle disease, fowl plague, and duck hepatitis viruses. The plaque morphology is described.
 ...
PMID:A plaque assay for duck plague virus. 1584 2

Alefacept is a fully human fusion protein for use in adult patients with moderate to severe chronic plaque psoriasis. Its dual mechanism of action involves inhibition of T-cell activation and selective reduction of memory T cells. We report the clinical course of two patients with hepatitis C virus (HCV) infection who have received alefacept for psoriasis. Consistent with its mechanism of action, administration of alefacept led to transient decreases in CD4+ and CD8+ T-cell counts. However, these reductions were not associated with an increase in HCV viral load or exacerbation of infection. Liver enzymes remained stable throughout the treatment and follow-up periods. Alefacept has a selective mechanism of action that specifically targets memory T cells and this selectivity may account for its safety and tolerability in patients with hepatitis.
 ...
PMID:Treatment of psoriasis with alefacept in patients with hepatitis C infection: a report of two cases. 1588 69

La Crosse virus (LACV) belongs to the Bunyaviridae family and causes severe encephalitis in children. It has a negative-sense RNA genome which consists of the three segments L, M, and S. We successfully rescued LACV by transfection of just three plasmids, using a system which was previously established for Bunyamwera virus (Lowen et al., Virology 330:493-500, 2004). These cDNA plasmids represent the three viral RNA segments in the antigenomic orientation, transcribed intracellularly by the T7 RNA polymerase and with the 3' ends trimmed by the hepatitis delta virus ribozyme. As has been shown for Bunyamwera virus, the antigenomic plasmids could serve both as donors for the antigenomic RNA and as support plasmids to provide small amounts of viral proteins for RNA encapsidation and particle formation. In contrast to other rescue systems, however, transfection of additional support plasmids completely abrogated the rescue, indicating that LACV is highly sensitive to overexpression of viral proteins. The BSR-T7/5 cell line, which constitutively expresses T7 RNA polymerase, allowed efficient rescue of LACV, generating approximately 10(8) infectious viruses per milliliter. The utility of this system was demonstrated by the generation of a wild-type virus containing a genetic marker (rLACV) and of a mutant with a deleted NSs gene on the S segment (rLACVdelNSs). The NSs-expressing rLACV formed clear plaques, displayed an efficient host cell shutoff, and was strongly proapoptotic. The rLACVdelNSs mutant, by contrast, exhibited a turbid-plaque phenotype and a less-pronounced shutoff and induced little apoptosis. Nevertheless, both viruses grew in Vero cells to similar titers. Our reverse genetics system now enables us to manipulate the genome of LACV in order to characterize its virulence factors and to develop potential vaccine candidates.
 ...
PMID:Efficient cDNA-based rescue of La Crosse bunyaviruses expressing or lacking the nonstructural protein NSs. 1605 34

Salad vegetables exposed to fecal contamination may cause outbreaks of hepatitis or gastro-enteritis if they are eaten raw. A procedure, based on elution with phosphate-buffered saline and concentration by filtration through membrane filters, was developed for the recovery of enteric viruses from salad leaves. The method was evaluated using lettuce leaves inoculated with hepatitis A virus (HAV), poliovirus, and MS2 bacteriophage. In addition, this method was validated by an intra-laboratory study using leaves of various salad vegetables inoculated with MS2 phage. The French standard NF V 03-110 was used to establish the general principle and the technical protocol of the validation procedure. Linear regression models describing the quantitative reactions were good fits to data in the whole range of viral concentrations tested, which was from about 1 to 4 log plaque-forming units (PFU) per 25 g of lettuce. The fractions of inoculated viruses recovered were estimated to be about 64% for HAV, 18% for poliovirus, and 29% for MS2. No significant effect of the food matrix was found using various types of salad vegetable (butter lettuce, iceberg lettuce, romaine lettuce, witloof chicory, curly endive, corn salad, rocket and watercress). Moreover, the variance of the results was constant for all levels of virus contamination within the experimental range. Intermediate reproducibility experiments were also performed to allow calculation of the uncertainty factor, which was found to be 0.58 log PFU/25 g. When used in association with phage enumeration, this validated procedure is rapid enough to be used for screening salad vegetables for evaluation of the efficacy of processes for control of pathogenic microorganisms on such foods.
 ...
PMID:Intra-laboratory validation of a concentration method adapted for the enumeration of infectious F-specific RNA coliphage, enterovirus, and hepatitis A virus from inoculated leaves of salad vegetables. 1638 77

The coronavirus nucleocapsid (N) protein is a multifunctional viral gene product that encapsidates the RNA genome and also plays some as yet not fully defined role in viral RNA replication and/or transcription. A number of conserved negatively charged amino acids are located within domain III in the carboxy end of all coronavirus N proteins. Previous studies suggested that the negatively charged residues are involved in virus assembly by mediating interaction between the membrane (M) protein carboxy tail and nucleocapsids. To determine the importance of these negatively charged residues, a series of alanine and other charged-residue substitutions were introduced in place of those in the N gene within a mouse hepatitis coronavirus A59 infectious clone. Aspartic acid residues 440 and 441 were identified as functionally important. Viruses could not be isolated when both residues were replaced by positively charged amino acids. When either amino acid was replaced by a positively charged residue or both were changed to alanine, viruses were recovered that contained second-site changes within N, but not in the M or envelope protein. The compensatory role of the new changes was confirmed by the construction of new viruses. A few viruses were recovered that retained the D441-to-arginine change and no compensatory changes. These viruses exhibited a small-plaque phenotype and produced significantly less virus. Overall, results from our analysis of a large panel of plaque-purified recovered viruses indicate that the negatively charged residues at positions 440 and 441 are key residues that appear to be involved in virus assembly.
 ...
PMID:Identification of functionally important negatively charged residues in the carboxy end of mouse hepatitis coronavirus A59 nucleocapsid protein. 1661 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>