Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Influenza A viruses are RNA viruses that contain negative-sense, single-stranded, and segmented RNA genome, which depends on virally encoded RNA-dependent RNA polymerase and cellular DNA-dependent RNA polymerase for replication of viral genome and transcription of viral mRNA, respectively. Hemagglutinin (HA), one of the major surface proteins of the influenza virus, is responsible for virus attachment to the receptor of host cells to initiate an infection. Amino acid (AA) substitutions in HA may cause changes in virus antigenicity and even receptor specificity. To detect the AA substitutions within HA at protein level, nanoelectrospray-MS/MS was used to analyze tryptic digestion of HA antigen directly purified from virus particles of an avian influenza virus, A/WDK/JX/12416/2005 (H1N1), of which the HA gene was sequenced as a reference. The comparison of the sequences obtained from analysis of viral genome and peptide found seven variations between HA gene and protein, namely E103K, R130K, T169I, I338V, N387S, S398I/L, and I399S in HA. Because influenza virus uses different polymerase machineries for replication and transcription, these substitutions could be introduced in the viral genome through replication process but not in viral mRNA in the transcription. The results, for the first time, provided experimental evidence showing differences in AA sequence obtained from direct analysis of viral protein derived from viral genome.
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PMID:Mutations in influenza virus replication and transcription: detection of amino acid substitutions in hemagglutinin of an avian influenza virus (H1N1). 1955 5

The epidemiology, symptomology, and viral aetiology of endemic influenza remain largely uncharacterized in Cambodia. In December 2006, we established passive hospital-based surveillance to identify the causes of acute undifferentiated fever in patients seeking healthcare. Fever was defined as tympanic membrane temperature >38 degrees C. From December 2006 to December 2008, 4233 patients were screened for influenza virus by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Of these patients, 1151 (27.2%) were positive for influenza. Cough (68.8% vs. 50.5%, P < 0.0001) and sore throat (55.0% vs. 41.9%, P < 0.0001) were more often associated with laboratory-confirmed influenza-infected patients compared to influenza-negative enrollees. A clear influenza season was evident between July and December with a peak during the rainy season. Influenza A and B viruses were identified in 768 (66.3%) and 388 (33.7%) of the influenza-positive population (n = 1153), respectively. In December 2008, passive surveillance identified infection of the avian influenza virus H5N1 in a 19-year-old farmer from Kandal province who subsequently recovered. From a subset of diagnostic samples submitted in 2007, 15 A(H1N1), seven A(H3N2) and seven B viruses were isolated. The predominant subtype tested was influenza A(H1N1), with the majority antigenically related to the A/Solomon Island/03/2006 vaccine strain. The influenza A(H3N2) isolates and influenza B viruses analysed were closely related to A/Brisbane/10/2007 or B/Ohio/01/2005 (B/Victoria/2/87-lineage) vaccine strains, respectively. Phylogenetic analysis of the HA1 region of the HA gene of influenza A(H1N1) viruses demonstrated that the Cambodian isolates belonged to clade 2C along with representative H1N1 viruses circulating in SE Asia at the time. These viruses remained sensitive to oseltamivir. In total, our data suggest that viral influenza infections contribute to nearly one-fifth of acute febrile illnesses and demonstrate the importance of influenza surveillance in Cambodia.
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PMID:Influenza epidemiology and characterization of influenza viruses in patients seeking treatment for acute fever in Cambodia. 1969 13

To investigate novel NS1-interacting proteins, we conducted a yeast two-hybrid analysis, followed by co-immunoprecipitation assays. We identified heterogeneous nuclear ribonucleoprotein F (hnRNP-F) as a cellular protein interacting with NS1 during influenza A virus infection. Co-precipitation assays suggest that interaction between hnRNP-F and NS1 is a common and direct event among human or avian influenza viruses. NS1 and hnRNP-F co-localize in the nucleus of host cells, and the RNA-binding domain of NS1 directly interacts with the GY-rich region of hnRNP-F determined by GST pull-down assays with truncated proteins. Importantly, hnRNP-F expression levels in host cells indicate regulatory role on virus replication. hnRNP-F depletion by small interfering RNA (siRNA) shows 10- to 100-fold increases in virus titers corresponding to enhanced viral RNA polymerase activity. Our results delineate novel mechanism of action by which NS1 accelerates influenza virus replication by modulating normal cellular mRNA processes through direct interaction with cellular hnRNP-F protein.
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PMID:Direct interaction of cellular hnRNP-F and NS1 of influenza A virus accelerates viral replication by modulation of viral transcriptional activity and host gene expression. 2342 46

The influenza RNA polymerase is known to be important in pathogenicity and adaptation of avian influenza viruses to mammalian hosts. However, the molecular mechanisms responsible are only partly understood. Here we investigated the role of the polymerase in two different, closely related, H5N1 influenza viruses - a high pathogenic, A/duck/Fujian/01/2002 (FJ) strain and a low pathogenic, A/duck/Guangxi/53/2002 (GX) strain. The polymerase activity of the FJ strain was significantly greater than the GX strain. Experiments with hybrid polymerase constructs - both in vitro and in ribonucleoprotein cell-based assays, suggested that the PA and to a lesser extent the PB2 subunits of the polymerase, were responsible for increased polymerase activity of the high pathogenic strain. However, promoter binding was inversely correlated with polymerase activity implying that excessive promoter binding inhibited polymerase activity by preventing promoter clearance. Overall, we suggest that the influenza polymerase is one of the determinants of pathogenicity of duck H5N1 viruses.
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PMID:Correlation between polymerase activity and pathogenicity in two duck H5N1 influenza viruses suggests that the polymerase contributes to pathogenicity. 2021 80

Low pathogenic avian influenza H6N2 viruses were biologically characterized by infecting chickens and ducks in order to compare adaptation of these viruses in these species. We examined the clinical signs, virus shedding, and immune response to infection in 4-wk-old white leghorn chickens and in 2-wk-old Pekin ducks. Five H6N2 viruses isolated between 2000 and 2004 from chickens in California, and one H6N2 virus isolated from chickens in New York in 1998, were given intrachoanally at a dose of 1 x 10(6) 50% embryo infectious dose per bird. Oral-pharyngeal and cloacal swabs were taken at 2, 4, and 7 days postinoculation (PI) and tested by real-time reverse-transcriptase polymerase chain reaction for presence of virus. Serum was collected at 7, 14, and 21 days PI and examined for avian influenza virus antibodies by commercial enzyme-linked immunosorbent assay (ELISA) and hemagglutination inhibition (HI) testing. Virus shedding for all of the viruses was detected in the oral-pharyngeal swabs from chickens at 2 and 4 days PI, but only three of the five viruses were detected at 7 days PI. Only two viruses were detected in the cloacal swabs from the chickens. Virus shedding for four of the five viruses was detected in the oral-pharyngeal cavity of the ducks, and fecal shedding was detected for three of the viruses (including the virus not shed by the oral-pharyngeal route) in ducks at 4 and 7 days PI. All other fecal swabs from the ducks were negative. Fewer ducks shed virus compared to chickens. Both the chickens and the ducks developed antibodies, as evidenced by HI and ELISA titers. The data indicate that the H6N2 viruses can infect both chickens and ducks, but based on the number of birds shedding virus and on histopathology, the viruses appear to be more adapted to chickens. Virus shedding, which could go unnoticed in the absence of clinical signs in commercial chickens, can lead to transmission of the virus among poultry. However, the viruses isolated in 2004 did not appear to replicate or cause more disease than earlier virus isolates.
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PMID:Biologic characterization of chicken-derived H6N2 low pathogenic avian influenza viruses in chickens and ducks. 2040 10

Newcastle disease virus (NDV) and avian influenza virus (AIV) are pathogens of major economic and social importance, and the diseases they cause are often devastating, particularly in domestic poultry. Both viruses are naturally found in a wide variety of wild birds, particularly aquatic species, where asymptomatic infection typically occurs. Wild birds are therefore considered to be a natural reservoir for both viruses. Wild birds kept in captivity are in an environment that promotes transmission of infection with both influenza and Newcastle disease viruses. This report describes a survey for the detection of antibodies against Newcastle disease and avian influenza A viruses using the hemagglutination inhibition test in samples from 88 wild birds from 38 species in four Bulgarian zoos. Samples with positive results against NDV were also tested against avian paramyxovirus type 3 (APMV-3). Real-time reverse-transcriptase PCR was also performed to detect viral RNA of NDV and AIV among 127 wild birds from 57 species from the same zoos. In 13 samples from seven avian species (ten birds from the family Phasianidae, two from the family Numidae, and one from the family Columbidae), antibodies against APMV-1 were detected. Seven birds, whose sera were APMV-1 positive, had been vaccinated. The other six birds (five Phasianidae representatives and one of the Columbidae family) had no immunization history. No antibodies against both H5 and H7 AIV and against APMV-3 were detected, and no RNA of NDV and AIV were detected.
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PMID:Status of wild birds in Bulgarian zoos with regard to orthomyxovirus and paramyxovirus type 1 infections. 2052 60

The PB2 subunit of the influenza virus RNA polymerase is a major virulence determinant of influenza viruses. However, the molecular mechanisms involved remain unknown. It was previously shown that the PB2 protein, in addition to its nuclear localization, also accumulates in the mitochondria. Here, we demonstrate that the PB2 protein interacts with the mitochondrial antiviral signaling protein, MAVS (also known as IPS-1, VISA, or Cardif), and inhibits MAVS-mediated beta interferon (IFN-beta) expression. In addition, we show that PB2 proteins of influenza viruses differ in their abilities to associate with the mitochondria. In particular, the PB2 proteins of seasonal human influenza viruses localize to the mitochondria while PB2 proteins of avian influenza viruses are nonmitochondrial. This difference in localization is caused by a single amino acid polymorphism in the PB2 mitochondrial targeting signal. In order to address the functional significance of the mitochondrial localization of the PB2 protein in vivo, we have generated two recombinant human influenza viruses encoding either mitochondrial or nonmitochondrial PB2 proteins. We found that the difference in the mitochondrial localization of the PB2 proteins does not affect the growth of these viruses in cell culture. However, the virus encoding the nonmitochondrial PB2 protein induces higher levels of IFN-beta and, in an animal model, is attenuated compared to the isogenic virus encoding a mitochondrial PB2. Overall this study implicates the PB2 protein in the regulation of host antiviral innate immune pathways and suggests an important role for the mitochondrial association of the PB2 protein in determining virulence.
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PMID:The PB2 subunit of the influenza virus RNA polymerase affects virulence by interacting with the mitochondrial antiviral signaling protein and inhibiting expression of beta interferon. 2053 52

Avian influenza virus (AIV) is an infectious agent of birds and mammals. AIV is causing huge economic loss and can be a threat to human health. Reverse transcriptase polymerase chain reaction (RT-PCR) has been used as a method for the detection and identification of AIV virus. Although RT-PCR is a sensitive method for detection of AIV, it requires sample preparation including separation and purification of AIV and concentrate viral RNA. It is laborious and complex process especially for diagnosis using faecal sample. In this study, magnetic beads were used for immunoseparation of AIV in chicken faecal sample by a magnetic microsystem. Using this system, all the 16 hemagglutinin (H) and 9 neuraminidase (N) subtypes of AIV were separated and detected in spiked faecal samples using RT-PCR, without an RNA extraction step. This rapid sample preparation method can be integrated with a total analysis microsystem and used for diagnosis of AIV.
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PMID:Rapid sample preparation for detection and identification of avian influenza virus from chicken faecal samples using magnetic bead microsystem. 2067 Jun 56

There are three types of influenza viruses: A, B, C. These viruses evolves constantly due to two main characteristics: the first one is the lack of the correction ability of the viral polymerase which causes the accumulation of single nucleotide mutations in the viral genes introduced by an error-prone viral RNA polymerase, (antigenic shift). The second one is the nature of their genome, formed by eight segments, which allows the interchange of genes between two different viral strains (antigenic drift). This viral plasticity, has allowed to the influenza A viruses to infect new host species and to cause infections with a pandemic characteristics. The Spanish influenza surveillance system, SVGE (its Spanish acronym), arises as a response to the possibility of facing a pandemic situation, especially after the transmission of avian influenza viruses to humans. This surveillance system is formed by sixteen physician and paediatrics network, nineteen epidemiological services coordinated by the National Epidemiological Centre (CNE) and eighteen laboratories , the Spanish Laboratories of Influenza network (ReLEG), coordinated by the National Centre of Microbiology. The aim of this article is to show the action of the ReLEG, in the pandemic caused by the influenza virus A(H1N1) during the season 2009-2010. The main objective of this network is the surveillance of the circulating viruses by means of their detection and their subsequent antigenic and genetic characterization, including the detection of resistance mutations against the main drugs, such as Oseltamivir.
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PMID:[Pandemic influenza A(H1N1): the experience of the Spanish Laboratories of Influenza Network (ReLEG)]. 2120 14

The endemic of Avian Influenza Virus (AIV) in Asia and epizootics in some European regions have caused serious economic losses. Multiplex reverse-transcriptase (RT) PCR has been developed to detect and subtype AIV. However, the number of targets that can be amplified in a single run is limited because of uncontrollable primer-primer interferences. In this paper, we describe a lab-on-a-chip device for fast AIV screening by integrating DNA microarray-based solid-phase PCR on a microfluidic chip. A simple UV cross-linking method was used to immobilize the DNA probes on unmodified glass surface, which makes it convenient to integrate microarray with microfluidics. This solid-phase RT-PCR method combined RT amplification of extracted RNA in the liquid phase and species-specific nested PCR on the solid phase. Using the developed approach, AIV viruses and their subtypes were unambiguously identified by the distinct patterns of amplification products. The whole process was reduced to less than 1 hour and the sample volume used in the microfluidic chip was at least 10 times less than in the literature. By spatially separating the primers, highly multiplexed amplification can be performed in solid-phase PCR. Moreover, multiplex PCR and sequence detection were done in one step, which greatly simplified the assay and reduced the processing time. Furthermore, by incorporating the microarray into a microchamber-based PCR chip, the sample and the reagent consumption were greatly reduced, and the problems of bubble formation and solution evaporation were effectively prevented. This microarray-based PCR microchip can be widely employed for virus detection and effective surveillance in wild avian and in poultry productions.
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PMID:A lab-on-a-chip device for rapid identification of avian influenza viral RNA by solid-phase PCR. 2136 71


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