Antisera to the type-specific internal influenza virus matrix (M) protein of a type A influenza virus were produced in goats. In the presence of complement, anti-M serum was cytotoxic for target cells which were infected with a variety of serologically distinct type A influenza viruses, but did not react with type B influenza virus-infected cells. Absorption experiments indicated that anti-M serum detected a common antigen(s) on the surface of type A-infected cells. This serological cross-reactivity parallels the cross-reactivity observed for the cytotoxic T-cell response to type A viruses. ...
Influenza virus M2 and PB1-F2 proteins have been proposed to activate the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in macrophages by altering intracellular ionic balance or mitochondrial reactive oxygen species (ROS) production. However, the precise mechanism by which these viral proteins trigger the NLRP3 inflammasome activation remains unclear. Here we show that influenza virus stimulates oxidized DNA release from macrophages. Ion channel activity of the M2 protein or mitochondrial localization of the PB1-F2 protein was required for oxidized DNA release. The oxidized DNA enhanced influenza virus-induced IL-1β secretion, whereas inhibition of mitochondrial ROS production by antioxidant Mito-TEMPO decreased the virus-induced IL-1β secretion. In addition, we show that influenza virus stimulates IL-1β secretion from macrophages in an AIM2-dependent manner. These results provide a missing link between influenza viral proteins and the NLRP3 inflammasome activation ...
TY - JOUR. T1 - Partitioning of proteins into plasma membrane microdomains. Clustering of mutant influenza virus hemagglutinins into coated pits depends on the strength of the internalization signal. AU - Fire, Ella. AU - Brown, Claire M.. AU - Roth, Michael G.. AU - Henis, Yoav I.. AU - Petersen, Nils O.. PY - 1997/11/21. Y1 - 1997/11/21. N2 - Internalization of membrane proteins involves their recruitment into plasma membrane clathrin-coated pits, with which they are thought to interact by binding to AP-2 adaptor protein complexes. To investigate the interactions of membrane proteins with coated pits at the cell surface, we applied image correlation spectroscopy to measure directly and quantitatively the clustering of influenza hemagglutinin (HA) protein mutants carrying specific cytoplasmic internalization signals. The HA system enables direct comparison between isolated internalization signals, because HA itself is excluded from coated pits. The studies presented here provide, for the first ...
Influenza virus NS2 is well known for its role in vRNP (viral RNP) nuclear export; however, its function has not been fully understood. A recent study showed that NS2 might interact with HIST1H1C (H1C, H1.2). Histones have been found to affect influenza virus replication, such as the H2A, H2B, H3 and H4, but H1 has not been detected. Here, we found that H1C interacts with NS2 via its C-terminal in the nucleus and that H1C affects influenza virus replication. The H1N1 influenza virus replicates better in H1C knockout A549 cells compared to wild-type A549 cells, primarily because of the regulation of H1C on IFN-β. Further studies showed that the H1C phosphorylation mutant (T146A) decreases IFN-β, while H1C methylation mutants (K34A, K187A) increases IFN-β by releasing the nucleosome and promoting IRF3 binding to the IFN-β promoter. Interestingly, NS2 interacts with H1C, which reduces H1C-IRF3 interaction and results in the inhibition of IFN-β enhanced by H1C. In summary, our study reveals a novel
Hemagglutinin (HA) of influenza viruses is a cylindrically shaped homotrimer, where each monomer comprises two disulfide-linked subdomains HA1 and HA2. Influenza infection is initiated by binding of HA1 to its host cell receptors and followed by the fusion between viral and host endosomal membranes mediated by HA2. Human influenza viruses preferentially bind to sialic acid that is linked to galactose by an α2,6-linkage (α2,6), whereas avian and swine influenza viruses preferentially recognize α2,3 or α 2,3/α2,6. For animal influenza viruses to cross host species barriers, their HA proteins must acquire mutations to gain the capacity to allow human-to-human transmission. In this study, the informational spectrum method (ISM), a bioinformatics approach, was applied to identify mutations and to elucidate the contribution to the receptor binding specificity from each mutation in HA1 in various subtypes within or between hosts, including 2009 human H1N1, avian H5N1, human H5N1, avian H1N1, and swine
PEARCE, J. M., REEVES, A. B., RAMEY, A. M., HUPP, J. W., IP, H. S., BERTRAM, M., PETRULA, M. J., SCOTTON, B. D., TRUST, K. A., MEIXELL, B. W. and RUNSTADLER, J. A. (2011), Interspecific exchange of avian influenza virus genes in Alaska: the influence of trans-hemispheric migratory tendency and breeding ground sympatry. Molecular Ecology, 20: 1015-1025. doi: 10.1111/j.1365-294X.2010.04908.x ...
Influenza A virus causes influenza in birds and some mammals, and is the only species of influenza virus A genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon. Some isolates of influenza A virus cause severe disease both in domestic poultry and, rarely, in humans. Occasionally, viruses are transmitted from wild aquatic birds to domestic poultry, and this may cause an outbreak or give rise to human influenza pandemics. Influenza A viruses are negative-sense, single-stranded, segmented RNA viruses. The several subtypes are labeled according to an H number (for the type of hemagglutinin) and an N number (for the type of neuraminidase). There are 18 different known H antigens (H1 to H18) and 11 different known N antigens (N1 to N11). H17 was isolated from fruit bats in 2012. H18N11 was discovered in a Peruvian bat in 2013. Each virus subtype has mutated into a variety of strains with differing ...
Recovery from live influenza trojan infection is known to induce heterosubtypic immunity. in lungs and in sera play a major part in conferring protecting immunity against heterosubtypic challenge. This study offers significant implications for developing broadly cross-reactive vaccines against newly growing pathogenic influenza viruses. Influenza A trojan neuraminidase and hemagglutinin glycoproteins will be the main goals of neutralizing antibodies. Predicated on the antigenic deviation of the two proteins, different influenza A infections with different combos of hemagglutinin (H1 to H16) and neuraminidase (N1 to N9) subtypes have already been discovered (7). Influenza trojan an infection or live intranasal vaccines stimulate immune system responses offering not only security against the homologous trojan but also cross-protection against lethal an infection with some heterologous strains of different subtypes in mice (1, 4, 6, 19, 20, Telatinib 23, 26). In human beings, natural an infection ...
The enormous toll on human life during the 1918-1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5 …
Protective immunity against influenza virus infection is mediated by neutralizing antibodies, but the precise role of T cells in human influenza immunity is uncertain. We conducted influenza infection studies in healthy volunteers with no detectable antibodies to the challenge viruses H3N2 or H1N1. We mapped T cell responses to influenza before and during infection. We found a large increase in influenza-specific T cell responses by day 7, when virus was completely cleared from nasal samples and serum antibodies were still undetectable. Preexisting CD4+, but not CD8+, T cells responding to influenza internal proteins were associated with lower virus shedding and less severe illness. These CD4+ cells also responded to pandemic H1N1 (A/CA/07/2009) peptides and showed evidence of cytotoxic activity. These cells are an important statistical correlate of homotypic and heterotypic response and may limit severity of influenza infection by new strains in the absence of specific antibody responses. Our results
For patient information click here For more information about non-human (variant) influenza viruses that may be transmitted to humans, see Zoonotic influenza Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]; Ammu Susheela, M.D. [3] Synonyms and Keywords: Flu; influenza A; influenza B; influenza C; human influenza; human influenza virus ...
Changes in influenza viruses require regular reformulation of strain-specific influenza vaccines. Vaccines based on conserved antigens provide broader protection. Influenza matrix protein 2 (M2) is highly conserved across influenza A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice with M2 peptide of a widely shared consensus sequence. This vaccination induced antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A DNA vaccine expressing full-length consensus-sequence M2 (M2-DNA) induced M2-specific antibody responses and protected against challenge with lethal influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus expressing M2 (M2-Ad) had enhanced antibody responses that cross-reacted with human and avian M2 sequences and induced T-cell responses. This M2 prime-boost vaccination conferred broad protection against challenge with lethal influenza A, including an H5N1 strain. Vaccination with M2, with key sequences represented,
TY - JOUR. T1 - Mechanism of action of the suppression of influenza virus replication by Ko-Ken Tang through inhibition of the phosphatidylinositol 3-kinase/Akt signaling pathway and viral RNP nuclear export. AU - Wu, Ming Sian. AU - Yen, Hung Rong. AU - Chang, Chia Wen. AU - Peng, Tsui Yi. AU - Hsieh, Chung Fan. AU - Chen, Chi Jene. AU - Lin, Tzou Yien. AU - Horng, Jim Tong. PY - 2011/4/12. Y1 - 2011/4/12. N2 - Aims of the study: Ko-Ken Tang (KKT, aka kakkon-to), a conventional Chinese herbal medicine, has been used for the treatment of the common cold, fever and influenza virus infection. However, the underlying mechanism of its activity against influenza virus infection remains elusive. In this study, the antiviral effect and its underlying mechanism was evaluated, including the investigation of anti-influenza virus activity of KKT on MDCK cells and corresponding mechanism related to phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and its consecutive viral RNP nuclear export. ...
The antigenicity of the hemagglutinins (HA) of five influenza viruses of the A0 and A1 subtypes has been analyzed by means of monoclonal antibodies of murine origin produced in vitro. Secondary monoclonal anti-HA(PR8) antibodies were able to differentiate 14 antigenic determinants (or groups of determinants) on the HA of five influenza virus strains of the A0 and A1 subtypes. Taking into account that certain pairs of determinants delineated on heterologous HA may reflect the heterogeneity of the humoral immune response to a single homologous determinant, the presence of at least eight determinants (host cell-derived determinants not included) on the homologous HA of PR8 and probably on the HA of influenza viruses in general is postulated. Three types of HA-determinants of A0 and A1 influenza virus strains could be distinguished: strain-specific, partially shared, and determinant(s) common to all five virus strains tested. Roughly 40, 55, and 5%, respectively, of the secondary anti-PR8 antibodies ...
Serological assays based on hemagglutination inhibition (HI) are historically the most common way to determine antigenic characteristics of influenza A viruses, and the HI test also serves as a functional assay for detection of anti-influenza antibodies in sera.11 The HI test exploits the ability of influenza viruses to agglutinate red blood cells (RBCs), a characteristic for which the HA gene was named. Thus, an influenza virus can be identified as to its subtype in an HI assay. A standard concentration of influenza virus (antigen) and serial dilutions of HA-subtype-specific antiserum are mixed, and after a short incubation period, RBCs are added to the antigen-antibody mixture.12 If the serum antibodies bind to the viral hemagglutinin, hemagglutination is inhibited, and the RBCs settle to the bottom of the test well. Hemagglutination reactions are compared among the sets of antisera and viral antigens in a test panel, and assumptions are made concerning the antigenic relatedness of the viruses ...
Keywords: Bioinfomatics, data source, diagnostic, influenza, primer Launch Because the 1997 Hong Kong avian influenza epizootic, the interest from the global world and its own scientific community provides intensified on all areas of influenza. 1 It has increased a lot more within the last few years due to the come back of H5N1 in 2003. 2 , 3 Significant assets and expenditure by america (NIH, CDC, USDA, etc.) and a lot of countries throughout the global globe have already been produced in every area of influenza biology, in the regions of vaccines specifically, therapeutics, and diagnostics. Due to these efforts is a significant upsurge in the quantity of genomic data for influenza, which is higher than 60 today?000 nucleotide sequences and growing by hundreds weekly. To be able to shop the increasing quantity of buy 54-36-4 influenza series data and make it available to researchers many directories/websites have already been produced including NCBIs Influenza Trojan Reference (IVR), LANLs ...
Braciale, T J., "Immunologic recognition of influenza virus-infected cells. II. Expression of influenza a matrix protein on the infected cell surface and its role in recognition by cross-reactive cytotoxic t cells." (1977). Subject Strain Bibliography 1977. 1114 ...
Influenza is a respiratory disease affecting humans, a limited number of other mammals, and birds. Of the three genera of orthomyxoviruses affecting humans, influenza viruses B and C established permanent lineages in ancient times, whereas influenza A viruses continue to emerge from zoonotic reservoirs and cause annual epidemics and, at irregular intervals, pandemics. Aquatic birds of the world are natural reservoirs for 16 of the 17 known influenza subtypes, and 1 subtype has been characterized from bats. Only three hemagglutinin subtypes (H1, H2, and H3) have caused pandemics in humans; the H1 and H3 subtypes are currently circulating in swine; and the H3 subtype is currently the only remaining epidemic subtype in horses and appears to be establishing a permanent lineage in dogs. All 16 subtypes of influenza viruses in the aquatic bird reservoir occur as low-pathogenicity strains that replicate predominantly in the intestinal tract and cause limited symptoms of overt disease. Subtypes H5 and H7 have
Inhibition of viral replication by icIgA antibodies has only been observed with in vitro studies using epithelial cell lines in transwell cultures. This effect appears to involve an interaction between polymeric immunoglobulin A (pIgA) and viral particles within an intracellular compartment, since IgA is transported across polarized cells. Polyclonal guinea pig antisera against purified influenza A virus and mouse antisera prepared against Influenza A/H3N2 hemagglutinin (HA0) cleavage loop peptides, were used in confocal fluorescence microscopy to show specific staining of wild-type influenza H1N1 and H3N2 viruses in clinical specimens. The HA0 cleavage loop peptides used for intranasal immunization of mice were designed and synthesized from specific conserved regions of influenza A/H1N1 & A/H3N2 viruses. Anti-human secretory IgA antibodies were used to show co-localisation of influenza A virus and icIgA. The results showed specific immunofluorescent staining of influenza A/H3N2 (X31) (HA0 ...
Another technique is use of cell cultures to grow vaccine strains; such as genetically engineering baculovirus to express a gene that encodes an influenza coat protein such as hemagglutinin or neuraminidase. "A recent NIAID-supported Phase II clinical trial of a vaccine produced by Protein Sciences Corporation using this strategy showed that it is well tolerated and immunogenic; the company is[when?] conducting further clinical evaluation of this product. Other new pathways for producing influenza vaccines include DNA-based approaches and the development of broadly protective vaccines based on influenza virus proteins that are shared by multiple strains."[5]. AVI Bio Pharma Inc. has evidence of inhibition of multiple subtypes of influenza A virus in cell culture with Morpholino oligomers from the results of their labs and four independent research laboratories[when?]. "The key finding here is that our NEUGENE(R) therapeutics continue to show efficacy against all strains of influenza A, including ...
The influenza A virus subtypes H1N1, H1N2 and H3N2 are prevalent in pig populations worldwide. All scientific data point towards swine as the key host species for new human influenza pandemics, which have been suggested to evolve in pigs from viral genes of avian, human and porcine origin. Therefore, it is of major importance to record the evolution of swine influenza viruses in pigs, and in particular monitor hallmarks of adaptation to humans. The scope of this thesis was to increase the understanding of the genetics of swine influenza virus (SIV), and to investigate the importance of different viral gene markers in association with differences in pathogenicity of two viruses of H1N2 subtype in pigs. The results from this study demonstrate, for the first time, natural reassortment in H1N2 viruses in the pig populations of Sweden. These H1N2 viruses have an avian-like SIV H1N1 hemagglutinin (HA) and a European H3N2 SIV-like neuraminidase (NA). Nucleotide sequence comparison revealed significant ...
Influenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains that cause pandemics arise from avian influenza virus by genetic reassortment among influenza viruses and two surface glycoproteins HA and NA form the basis of serologically distinct virus types. The innate immune system recognizes invaded virus through multiple mechanisms. Viral non-structural NS1 protein is a multifunctional virulence factor that interfere IFN-mediated antiviral response. It inhibits IFN production by blocking activation of transcription factors such as NF-kappa B, IRF3 and AP1. NS1 further inhibits the activation of IFN-induced antiviral genes. PB1-F2 protein is another virulence factor that induce apoptosis of infected cells, which results in life-threatening bronchiolitis ...
Abstract: The emergence of human infections with a novel H7N9 influenza strain has raised global concerns about a potential human pandemic. To further understand the character of other influenza viruses of the H7 subtype, we selected two H7N1 avian influenza viruses (AIVs) isolated from wild birds during routine surveillance in China: A/Baers Pochard/Hunan/414/2010 (BP/HuN/414/10) (H7N1) and A/Common Pochard/Xianghai/420/2010 (CP/XH/420/10) (H7N1). To better understand the molecular characteristics of these two isolated H7N1 viruses, we sequenced and phylogenetically analyzed their entire genomes. The results showed that the two H7N1 strains belonged to a Eurasian branch, originating from a common ancestor. Phylogenetic analysis of their hemagglutinin (HA) genes showed that BP/HuN/414/10 and CP/XH/420/10 have a more distant genetic relationship with A/Shanghai/13/2013 (H7N9), with similarities of 91.6% and 91.4%, respectively. To assess the replication and pathogenicity of these viruses in different
We previously demonstrated that passively administered i.v. pIgA anti-influenza virus mAb could protect the murine nose against viral infection and that nasal immunity in the intact murine nose could be abrogated by the administration of anti-α-chain nose drops, but not by the administration of anti-γ or anti-μ-chain nose drops, suggesting that S-IgA was the major mediator of anti-influenza virus protection (10, 11). In contrast, Mbawuike et al. (13), using the IgA KO mouse, suggested that IgA was not necessary for nasal and pulmonary protection against influenza virus infection in mice immunized with influenza vaccine plus cholera toxin/cholera toxin B. Asahi et al. (14), however, reported that the blockade of transepithelial transport of pIgA in the pIgR KO mouse led to compromised nasal anti-influenza virus protection and the lack of IgA-dependent heterotypic cross-protection in the upper and lower RTs of vaccinated mice. A marked increase in serum influenza virus-specific IgA ...
View Notes - Extra Credit from GEN 300 at Clemson. Logistics of the Influenza Virus The influenza virus is separated in to three groups: A, B, and C. Influenza A and B are responsible for the
The M2 protein of influenza A virus is a small, nonglycosylated transmembrane protein that is expressed on surfaces of virus-infected cells. A monoclonal antibody specific for the M2 protein was used to investigate its expression in polarized epithelial cells infected with influenza virus or a recombinant vaccinia virus that expresses M2. The expression of M2 on the surfaces of influenza virus-infected cells was found to be restricted to the apical surface, closely paralleling that of the influenza virus hemagglutinin (HA). Membrane domain-specific immunoprecipitation indicated that the M2 protein was inserted directly into the apical membrane with transport kinetics similar to those of HA. In polarized cells infected with a recombinant vaccinia virus that expresses M2, we found that 86 to 93% of surface M2 was restricted to the apical domain compared with 88 to 90% of HA in a similar assay. These results indicate that the M2 protein undergoes directional transport in the absence of other ...
TY - JOUR. T1 - Influenza A viruses control expression of proviral human p53 isoforms p53β and Delta133p53α. AU - Terrier,Olivier. AU - Marcel,Virginie. AU - Cartet,Gaelle. AU - Lane,David P.. AU - Lina,Bruno. AU - Rosa-Calatrava,Manuel. AU - Bourdon,Jean-Christophe. PY - 2012/8. Y1 - 2012/8. N2 - Previous studies have described the role of p53 isoforms, including p53 beta and Delta 133p53 alpha, in the modulation of the activity of full-length p53, which regulates cell fate. In the context of influenza virus infection, an interplay between influenza viruses and p53 has been described, with p53 being involved in the antiviral response. However, the role of physiological p53 isoforms has never been explored in this context. Here, we demonstrate that p53 isoforms play a role in influenza A virus infection by using silencing and transient expression strategies in human lung epithelial cells. In addition, with the help of a panel of different influenza viruses from different subtypes, we also show ...
Since the highly pathogenic H5N1 influenza caused thousands of deaths of wild bird in this area in 2005, Qinghai Lake in China has become a hot spot for study of the influence of avian influenza to migratory wild birds. However, the ecology and evolution of low pathogenic avian influenza virus in this region are limited. This project-based avian influenza surveillance in Qinghai lake region was initiated in year 2012. Samples of wild bird feces and lake surface water were collected in Qinghai Lake in year 2012.Virus isolation was conducted on embryonated chicken eggs. The influenza A virus was determined by rRT-PCR. Virus sequences were acquired by deep sequencing. The phylogenetic correlation and molecular characteristics of the viruses were analyzed. The virus growth and infection features, receptor binding preference were studied, and pathogenicity in vitro as well as. Two H13N8 subtype influenza viruses were isolated. The viruses are phylogenetically belong to Eurasian lineage. Most of the genes are
T lymphocytes play a primary role in recovery from viral infections and in antiviral immunity. Although viral-specific CD8+ and CD4+ T cells have been shown to be able to lyse virally infected targets in vitro and promote recovery from lethal infection in vivo, the role of CD4+ T lymphocytes and their mechanism(s) of action in viral immunity are not well understood. The ability to further dissect the role that CD4+ T cells play in the immune response to a number of pathogens has been greatly enhanced by evidence for more extensive heterogeneity among the CD4+ T lymphocytes. To further examine the role of CD4+ T cells in the immune response to influenza infection, we have generated influenza virus-specific CD4+ T cell clones from influenza-primed BALB/c mice with differential cytokine secretion profiles that are defined as T helper type 1 (Th1) clones by the production of interleukin 2 (IL-2) and interferon gamma (IFN-gamma), or as Th2 clones by the production of IL-4, IL-5, and IL-10. Our ...
by Vetscite. Because fatal infections with highly pathogenic avian influenza A (HPAI) virus subtype H5N1 have been reported in birds of prey, we sought to determine detailed information about the birds susceptibility and protection after vaccination. Ten falcons vaccinated with an inactivated influenza virus (H5N2) vaccine seroconverted. We then challenged 5 vaccinated and 5 nonvaccinated falcons with HPAI (H5N1). All vaccinated birds survived; all unvaccinated birds died within 5 days. For the nonvaccinated birds, histopathologic examination showed tissue degeneration and necrosis, immunohistochemical techniques showed influenza virus antigen in affected tissues, and these birds shed high levels of infectious virus from the oropharynx and cloaca. Vaccinated birds showed no influenza virus antigen in tissues and shed virus at lower titers from the oropharynx only. Vaccination could protect these valuable birds and, through reduced virus shedding, reduce risk for transmission to other avian ...
During the 2010-2011 flu season, CDC expects the 2009 H1N1 virus to cause illness again along with other influenza viruses. The 2010-2011 flu vaccine will protect against 2009 H1N1 and two other influenza viruses.. Getting vaccinated is the best way to get protected! CDC is now encouraging all people 6 months and older, including people older than 65, to get vaccinated. Students with Barry Aetna Student Insurance will be charged NO FEE for the vaccine. Students may also have the seasonal flu $20 fee billed to their student account. ...
Author Summary To deliver their genomes into host cells during entry, enveloped viruses contain glycoproteins that bind to cellular receptors and cause fusion of viral and cellular membranes. The influenza virus HA protein is the archetypal viral fusion glycoprotein, promoting entry by undergoing irreversible structural changes that drive membrane merger. HA trimers on the surfaces of infectious influenza virions are trapped in a metastable, high-energy conformation and are triggered to refold and cause membrane fusion after the virus is internalized and exposed to low pH. Here, we provide biochemical and x-ray crystallographic evidence that naturally occurring amino-acid variations at the interface of the vestigial esterase and fusogenic stalk domains alter HA acid stability for highly pathogenic H5N1 influenza, resulting in a shift in the threshold pH required to activate HA protein structural changes that cause membrane fusion. Furthermore, our data reveals that an increased HA activation pH
The segmented genome of an influenza virus is encapsidated into ribonucleoprotein complexes (RNPs). Unusually among RNA viruses, influenza viruses replicate in the nucleus of an infected cell, and their RNPs must therefore recruit host factors to ensure transport across a number of cellular compartments during the course of an infection. Recent studies have shed new light on many of these processes, including the regulation of nuclear export, genome packaging, mechanisms of virion assembly and viral entry and, in particular, the identification of Rab11 on recycling endosomes as a key mediator of RNP transport and genome assembly. This review uses these recent gains in understanding to describe in detail the journey of an influenza A virus RNP from its synthesis in the nucleus through to its entry into the nucleus of a new host cell.
The segmented genome of an influenza virus is encapsidated into ribonucleoprotein complexes (RNPs). Unusually among RNA viruses, influenza viruses replicate in the nucleus of an infected cell, and their RNPs must therefore recruit host factors to ensure transport across a number of cellular compartments during the course of an infection. Recent studies have shed new light on many of these processes, including the regulation of nuclear export, genome packaging, mechanisms of virion assembly and viral entry and, in particular, the identification of Rab11 on recycling endosomes as a key mediator of RNP transport and genome assembly. This review uses these recent gains in understanding to describe in detail the journey of an influenza A virus RNP from its synthesis in the nucleus through to its entry into the nucleus of a new host cell.
The EM experiments show that complete RNPs unwind to circular structures under both high and low salt conditions. This may suggest that the supercoiled structures of the influenza RNPs are possibly poised to be unwound, which may be important for replicative processes. The removal of the polymerase takes away a constraint at the vRNA ends. EM of polymerase‐free RNPs shows that the vRNA ends are free to rotate and unwind in the absence of the polymerase. The polymerase‐free influenza virus RNPs behave as linear structures and react very similarly to the linear RNPs of other negative strand RNA viruses, such as those from rhabdo‐ and paramyxoviruses, that can be uncoiled reversibly in low salt and coiled to very tight structures in high salt (Heggeness et al., 1980).. The influenza virus RNP appears to be assembled from two antagonistic proteins: nucleoprotein activity favours the melting of RNA secondary structures and exposes the bases to the environment, whereas the polymerase complex ...
The U.S. Food and Drug Administration today cleared for marketing a new, more rapid test for the detection of influenza A/H5N1, a disease-causing subtype of the avian influenza A virus that can infect humans. The test, called AVantage A/H5N1 Flu Test, detects influenza A/H5N1 in throat or nose swabs collected from patients who have flu-like symptoms. The test identifies in less than 40 minutes a specific protein (NS1) that indicates the presence of the influenza A/H5N1 virus subtype. Previous tests cleared by the FDA to detect this influenza A virus subtype can take three or four hours to produce results.
My research interests are centered on viruses, particularly influenza viruses, which are important human and animal pathogens causing widespread clinical and veterinary disease. My group focuses on the fundamental molecular mechanisms of influenza virus replication, aiming to understand the molecular determinants of host range and virulence of influenza viruses. By gaining further insights into the molecular aspects of influenza virus replication we hope to facilitate the development of novel strategies to combat influenza.. Specifically, we address questions ranging from how the influenza virus RNA polymerase transcribes and replicates the segmented negative-sense viral RNA genome in the nucleus of the infected cell to how the RNA genome is exported from the nucleus and assembles into infectious progeny virus particles. We are also interested in the role of host factors in viral replication as well as in understanding the effects of virus infection on the host cell, the molecular mechanisms of ...
Diagnostic methods for influenza infection that are routinely performed such as virus isolation and antigen detection are both sensitive and specific. The presence of molecular techniques for detection of influenza virus provides advantages for the investigation of respiratory outbreaks and may be essential for further epidemiology purposes such as evolutionary studies. This is the first report describing the development of primer sets to obtain complete coding sequence of HA and NA genes of influenza A/H3N2 virus that used Indonesian virus. As an archipelago country, the development of primer sets covering complete coding sequence of influenza A/H3N2 virus for further evolutionary studies has become a challenge in Indonesia. Maintaining the cold chain stability during specimen shipment become crucial for ILI surveillance in Indonesia.. The designed primer sets covering complete coding sequence of HA and NA gene of influenza A/H3N2 virus were developed based on the consideration that shorter PCR ...
Influenza virus polymerase uses a capped primer, derived by cap-snatching from host pre-messenger RNA, to transcribe its RNA genome into mRNA and a stuttering mechanism to generate the poly(A) tail. By contrast, genome replication is unprimed and generates exact full-length copies of the template. Here we use crystal structures of bat influenza A and human influenza B polymerases (FluA and FluB), bound to the viral RNA promoter, to give mechanistic insight into these distinct processes. In the FluA structure, a loop analogous to the priming loop of flavivirus polymerases suggests that influenza could initiate unprimed template replication by a similar mechanism. Comparing the FluA and FluB structures suggests that cap-snatching involves in situ rotation of the PB2 cap-binding domain to direct the capped primer first towards the endonuclease and then into the polymerase active site. The polymerase probably undergoes considerable conformational changes to convert the observed pre-initiation state into
Every year influenza virus causes seasonal epidemics that affect 5-10% of the world population and kill up to 500,000 people. In nature, the virus primarily infects aquatic birds which can further infect domestic chickens and pigs. Sporadically, the virus jumps the species barrier from these domestic animals to humans causing a world-wide pandemic that can infect 30-50% of the population in a single winter season. This is what may happen with the pandemic swine-origin H1N1 virus because few people have protective antibodies against it.. As with all genes, those of influenza virus need to be transcribed into messenger RNA (mRNA) that is subsequently translated into proteins by ribosomes. However, viruses have no metabolism of their own and must use the ribosomes of the cells they have infected. Therefore, the viral mRNA molecules must resemble cellular mRNAs otherwise the ribosomes will not recognise them. One of the characteristics of all cellular mRNAs is that they start with a molecular tag, a ...
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Influenza virus NS1 protein stimulates translation of the M1 protein.: The influenza virus NS1 protein was shown to stimulate translation of the M1 protein. M-C
Compositions and methods are provided for the treatment and diagnosis of influenza virus infections. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with viral RNAs. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, 5-untranslated sequences, 3-untranslated sequences, and intron/exon junction of influenza virus mRNAs. In additional preferred embodiments, the oligonucleotides are specifically hybridizable with RNA sequences involved in splicing of the viral RNA, or in viral packaging. Methods of treating animals suffering from influenza virus infection are disclosed.
To determine if fatal infections caused by different highly virulent influenza A viruses share the same pathogenesis, we compared 2 different influenza A virus subtypes, H1N1 and H5N1. The subtypes, which had shown no pathogenicity in laboratory mice, were forced to evolve by serial passaging. Although both adapted viruses evoked diffuse alveolar damage and showed a similar 50% mouse lethal dose and the same peak lung concentration, each had a distinct pathologic signature and caused a different course of acute respiratory distress syndrome. In the absence of any virus labeling, a histologist could readily distinguish infections caused by these 2 viruses. The different histologic features described in this study here refute the hypothesis of a single, universal cytokine storm underlying all fatal influenza diseases. Research is thus crucially needed to identify sets of virulence markers and to examine whether treatment should be tailored to the influenza virus pathotype.
Humans can be infected by influenza viruses types A,B, and C. Type A affects humans, birds, and pigs. Type B and C affect only humans. Type C is less severe than type A and it does not cause pandemics.. In this visualization by Information is Beautiful, we can see how the different strains of influenza virus affect humans, what is their origin, and how they are transmitted from pigs and from birds ultimately to humans.. Type A influenza is divided into H and N strains. The "swine flu" N1H1 killed 15,000 people worldwide in 2009-2010. The "bird flu" H5N1 strain, with a fatality rate of 60%, has killed 371 people as of 2013. The more recent H7N9 strain has killed thousand of pigs in China, with 8 human fatalities to date.. ...
Proteolytic cleavage of haemagglutinin (HA) is essential for the infectivity of influenza A viruses (IAVs). This is usually mediated by trypsin-like proteases present in the respiratory tract. However, the ability to use plasminogen (PLG) as an alternative protease may contribute to pathogenesis of IAV infections and virus replication outside the respiratory tract. It was demonstrated previously that neuraminidase (NA) of the IAV strain A/WSN/33 can sequester PLG, allowing this virus to replicate in a PLG-dependent fashion. However, PLG also promotes replication of other IAVs, although its mode of action is poorly understood. Here, using NA-deficient viruses, we demonstrate that NA is not required for the binding of PLG and subsequent cleavage of HA. However, we demonstrate that the cellular protein annexin 2 (A2) can bind PLG and contributes to PLG-dependent cleavage of HA and subsequent IAV replication. Collectively, these results indicate that PLG promotes IAV replication in an A2-dependent fashion
PatientID 0034181F-59AB-4B2C-A06A-A83EE1DF1A17 Influenza A 1 0084E706-90D0-4314-8C99-496171AB639D Influenza B 1 00EFD11D-650A-4317-8C4F-4B7378AD7946 Other 2 0118B486-8ACE-4BFF-8ED6-753D96E6B441 Influenza A 1 02C9FF5A-A4D6-461A-A650-E3EB405D62AE Influenza A 2 031C1231-B585-478F-A98F-35E017B788CD Other 2 035A053E-91B1-4B68-87D4-F92C675FE6E3 Other 2 03AA4AD0-1B0E-4CAD-BD76-03FE52AA580D Staphylococcus, coag neg 1 Epstein-Barr virus (EBV) 1 Hemophilus parainfluenzae 1 Influenza A 1 Pneumocystis carinii 1 03FA6416-FE28-484B-AC83-60A7442035BE Influenza A 1 040710D1-2D29-48F4-B14C-ABAD7F2DC3B4 Influenza A 1 04B6544B-76BD-475E-83B4-782E2387093C Influenza A 1 Candida albicans 1 04BB440E-3A59-4453-8648-72AA1FB7CE22 Influenza A 1 057101E0-8C51-441B-AA05-B52D0092D820 Influenza A 1 0630B500-DDCD-4882-B3F2-D4B6DCD0DE59 Enterovirus 1 063CA301-7E8A-47EE-B8E3-6F01E734FEB7 Other 2 06522594-1B6F-492D-B47C-D94460052212 Influenza A 1 06799A45-93D6-4AAB-AA45-02DACB2C0D27 Influenza A 1 ...
PatientID 0034181F-59AB-4B2C-A06A-A83EE1DF1A17 Influenza A 1 0084E706-90D0-4314-8C99-496171AB639D Influenza B 1 00EFD11D-650A-4317-8C4F-4B7378AD7946 Other 2 0118B486-8ACE-4BFF-8ED6-753D96E6B441 Influenza A 1 02C9FF5A-A4D6-461A-A650-E3EB405D62AE Influenza A 2 031C1231-B585-478F-A98F-35E017B788CD Other 2 035A053E-91B1-4B68-87D4-F92C675FE6E3 Other 2 03AA4AD0-1B0E-4CAD-BD76-03FE52AA580D Staphylococcus, coag neg 1 Epstein-Barr virus (EBV) 1 Hemophilus parainfluenzae 1 Influenza A 1 Pneumocystis carinii 1 03FA6416-FE28-484B-AC83-60A7442035BE Influenza A 1 040710D1-2D29-48F4-B14C-ABAD7F2DC3B4 Influenza A 1 04B6544B-76BD-475E-83B4-782E2387093C Influenza A 1 Candida albicans 1 04BB440E-3A59-4453-8648-72AA1FB7CE22 Influenza A 1 057101E0-8C51-441B-AA05-B52D0092D820 Influenza A 1 0630B500-DDCD-4882-B3F2-D4B6DCD0DE59 Enterovirus 1 063CA301-7E8A-47EE-B8E3-6F01E734FEB7 Other 2 06522594-1B6F-492D-B47C-D94460052212 Influenza A 1 06799A45-93D6-4AAB-AA45-02DACB2C0D27 Influenza A 1 ...
Description of disease H1N1 (swine) influenza. Treatment H1N1 (swine) influenza. Symptoms and causes H1N1 (swine) influenza Prophylaxis H1N1 (swine) influenza
The nucleotide sequences of the nucleoprotein (NP) genes of fowl plague virus (FPV) and of a temperature-sensitive (ts) mutant (ts81) derived therefrom have been determined. The ts81-NP nucleotide sequence possesses a single nucleotide substitution in comparison to the wild type. This causes an amin …