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

Torque Teno Virus (TTV) has been assigned to the floating genus Anellovirus. TTV ssDNA genomes have a size of 3.6 to 3.8 kb and display up to 30% nucleotide diversity. The pathogenic potential of TTV is under investigation. To address a putative link of pathogenicity with the observed sequence variations, the transcription profile of P/1C1 (genogroup 1) isolated from a patient diseased with a non A-G hepatitis was analysed. Four mRNAs were identified, which encoded the seven proteins ORF1, ORF1/1, ORF1/2, ORF2, ORF2/2, ORF3 and ORF4. Expression of the ORF1 protein and its splice variant ORF1/1 in cell culture was detected by an ORF1-specific antiserum. Analysis of N-terminal tagged P/1C1-encoded proteins revealed that ORF1, ORF1/1 and ORF1/2 were localised in the nucleoli, ORF3 and ORF4 resided in the nucleoplasm, ORF2/2 appeared either in the nucleoli or the whole nucleus while ORF2 was the only protein seen in the cytoplasm.
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PMID:Gene expression of the human Torque Teno Virus isolate P/1C1. 1879 80

Partial or complete deletion of several coronavirus nonstructural proteins (nsps), including open reading frame 1a (ORF1a)-encoded nsp2, results in viable mutant proteins with specific replication defects. It is not known whether expression of nsps from alternate locations in the genome can complement replication defects. In this report, we show that the murine hepatitis virus nsp2 sequence was tolerated in ORF1b with an in-frame insertion between nsp13 and nsp14 and in place of ORF4. Alternate encoding or duplication of the nsp2 gene sequence resulted in differences in nsp2 expression, processing, and localization, was neutral or detrimental to replication, and did not complement an ORF1a Deltansp2 replication defect. The results suggest that wild-type genomic organization and expression of nsps are required for optimal replication.
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PMID:Murine coronaviruses encoding nsp2 at different genomic loci have altered replication, protein expression, and localization. 1881 97

Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis in healthy individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going up to 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource-starved countries. No specific antiviral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success. Zinc is an essential micronutrient that plays crucial roles in multiple cellular processes. Zinc salts are known to be effective in reducing infections caused by few viruses. Here, we investigated the effect of zinc salts on HEV replication. In a human hepatoma cell (Huh7) culture model, zinc salts inhibited the replication of genotype 1 (g-1) and g-3 HEV replicons and g-1 HEV infectious genomic RNA in a dose-dependent manner. Analysis of a replication-defective mutant of g-1 HEV genomic RNA under similar conditions ruled out the possibility of zinc salts acting on replication-independent processes. An ORF4-Huh7 cell line-based infection model of g-1 HEV further confirmed the above observations. Zinc salts did not show any effect on the entry of g-1 HEV into the host cell. Furthermore, our data reveal that zinc salts directly inhibit the activity of viral RNA-dependent RNA polymerase (RdRp), leading to inhibition of viral replication. Taken together, these studies unravel the ability of zinc salts in inhibiting HEV replication, suggesting their possible therapeutic value in controlling HEV infection.IMPORTANCE Hepatitis E virus (HEV) is a public health concern in resource-starved countries due to frequent outbreaks. It is also emerging as a health concern in developed countries owing to its ability to cause acute and chronic infection in organ transplant and immunocompromised individuals. Although antivirals such as ribavirin have been used to treat HEV cases, there are known side effects and limitations of such therapy. Our discovery of the ability of zinc salts to block HEV replication by virtue of their ability to inhibit the activity of viral RdRp is important because these findings pave the way to test the efficacy of zinc supplementation therapy in HEV-infected patients. Since zinc supplementation therapy is known to be safe in healthy individuals and since high-dose zinc is used in the treatment of Wilson's disease, it may be possible to control HEV-associated health problems following a similar treatment regimen.
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PMID:Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase. 2881 17