Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kyasanur Forest Disease Virus (KFDV) is a tick-borne, hemorrhagic fever-causing member of the Flaviviridae virus family. With infections annually ranging from 50 to 1000 people in south-west India and the lack of effective treatments, a better understanding of this virus is needed. The development of a reverse genetics system (RGS) for KFDV would provide the opportunity to address these issues. The KFDV genome sequence was elucidated and the RGS was created. Utilizing this system, live infectious KFDV particles were produced from mammalian cell culture, thereby validating the success of the RGS. Flaviviruses have the ability to suppress the type 1 interferon response and indications are that the non structural (NS) proteins serve this role. Using luciferase bioassays, the NS5 protein of KFDV was determined to be the primary antagonist of the IFN response when compared to the other NS proteins, specifically NS4B and NS4B-2k. Moreover, our results indicate that this is attributed to a region, beginning before and including the RNA-dependent RNA polymerase (RdRp). With evasion of the interferon response by KFDV established, the further implementation of the reverse genetics system will enable investigation into pathogenesis and disease progression of KFDV with respect to the innate immune response, at the IFN and the NS5 protein levels.
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PMID:The generation of a reverse genetics system for Kyasanur Forest Disease Virus and the ability to antagonize the induction of the antiviral state in vitro. 2210 Apr 1

Alkhumra hemorrhagic fever virus (AHFV), a relatively new member of the Flaviviruses, was discovered in Saudi Arabia 23 years ago. AHFV is classified in the tick-borne encephalitis virus serocomplex, along with the Kyasanur forest disease virus (KFDV) and tick-borne encephalitis virus (TBEV). Currently, very little is known about the pathologies of AHFV. In this study, using the available genome information of AHFV, KFDV and TBEV, we have predicted and compared the following aspects of these viruses: evolution, nucleotide and protein compositions, recombination, codon frequency, substitution rate, N- and O-glycosylation sites, signal peptide and cleavage site, transmembrane region, secondary structure of 5' and 3' UTRs and RNA-RNA interactions. Additionally, we have modeled the 3D protease and RNA-dependent RNA polymerase structures for AHFV, KFDV and TBEV. Recombination analysis showed no evidence of recombination in the AHFV genome with that of either KFDV or TBEV, although single break point analysis showed that nucleotide position 7399 (in the NS4B) is a breakpoint location. AHFV, KFDV and TBEV are very similar in terms of codon frequency, the number of transmembrane regions, properties of the polyprotein, RNA-RNA interaction sequences, NS3 protease and NS5 polymerase structures and 5' UTR structure. Using genome sequences, we showed the similarities between these closely- related viruses on several different areas.
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PMID:Comparative genome analysis of Alkhumra hemorrhagic fever virus with Kyasanur forest disease and tick-borne encephalitis viruses by the in silico approach. 2974 1

Kyasanur forest disease (KFD) is a biphasic tick-borne disease which occurs during the post-monsoon season. The patient may visit the hospital in either of the phases, and it is essential to differentiate between the two phases as the management considerations in both phases are different. This is a retrospective review of patients diagnosed with KFD who were treated by the Infectious Disease Department between September 2019 and May 2020. A total of 14 cases (16 admissions) were diagnosed during the study period by reverse-transcriptase polymerase chain reaction assay. Of these, nine cases came to our hospital during the first phase and seven (including two-readmissions) came to our hospital during the second phase. The manifestations in the first phase included high-grade fever (100%), myalgia (67%), conjunctival suffusion (33%), palatal eruptions (78%), gastrointestinal manifestations (67%), leucopenia (100%), thrombocytopenia (89%), elevated transaminases (89%), elevated creatine phosphokinase (100%) and activated partial thromboplastin time (APTT) (100%). Manifestations in the second phase were fever (57%), headache (100%), blurring of vision (29%), neck signs (71%), leukocytosis (71%), thrombocytopenia (14%), elevated transaminases (40%) and APTT (20%). The clinical symptomatology and laboratory manifestations are different in each of the two phases and can be easily identified by primary care physicians.
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PMID:Difference in clinical presentation between the first and second phases of Kyasanur Forest disease: an experience from a teaching hospital in South India. 3325 36