As a major pathogen of human and certain animal species, influenza virus causes wide spread and potentially devastating disease. Influenza viruses belong to the orthomyxoviridae family, which consists of several genera. Here, we examined influenza virus entry and infection in lec1 cells, a mutant cho cell line deficient. Not all patients with flu have all of the clinical manifestations. Indonesias decision to withhold samples of avian influenza virus a h5n1 from the world health organization for much of 2007 caused a crisis in global health. Influenza virus is a major human pathogen that causes annual epidemics and occasional pandemics. Thus research to identify new antiinfluenza virus strategies would be useful.
The first step of influenza virus entry is the recognition of the host cell receptor molecule, terminal. The dr isotype of the human leukocyte antigen of the mhc class iior its homologues in bats, pigs, mice and chickensis an essential cell entry determinant for bat influenza a viruses. Membrane fusion is critical to eukaryotic cellular function and crucial to the entry of enveloped viruses such as influenza and human immunodeficiency virus. Compans, georg herrler, in mucosal immunology third edition, 2005. To date, conventional commercialized antiviral agents for iv have been. Evolution of therapeutic antibodies, influenza virus. Characterising viable virus from air exhaled by h1n1. Here, we examined influenza virus entry and infection in lec1 cells, a mutant cho cell line deficient in terminal nlinked glycosylation caused by a mutation in the n acetylglucosaminyltransferase i gnt1 gene.
Antiviral research on influenza virus research group. The ability of swine iavs to infect humans and cause pandemics such as that of the influenza ah1n1 virus observed during 2009 3,4 and the sporadic transmission of various swine influenza viruses, including h1n1 5, h3n2 6, and variant h3n2 7, are public health concerns and highlight the need for increased vigilance and understanding of. In more serious cases, influenza causes pneumonia, which can be fatal, particularly in young children. Above all, the influenza virus iv is recognized as a serious public health concern with 200,000 hospitalizations and 36,000 deaths annually in the united states alone.
Ha attachment to the receptor allows cellular entry of the virus. Symptoms of influenza usually appear after a period of about 2448 hours. Mechanistic studies indicated that these lead triterpenoids bind tightly to the. For influenza a virus, ha has been classified in 20 subtypes h1h20. Sialylated nlinked glycans have been reported to be essential for iav entry chu vc, whittaker gr 2004 proc natl acad sci usa 102. Influenza virus hemagglutinin recognizes sialyloligosaccharides of glycoproteins and glycolipids as cell surface receptors in the initial stage of the infection process. Porous gold nanoparticles for attenuating infectivity of. Viral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell and introduces viral material into the cell. Antiinfluenza virus effect of aqueous extracts from dandelion.
Role for influenza virus envelope cholesterol in virus entry and. H1n1 virus from the 2009 pandemic and the h5n1 and. Hence, the place is vulnerable to the spread of influenza in the event ofan epidemic in mainland china. We propose that multiple receptors are used by influenza virus, mediating entry either independently of sialic acid or via a multistep entry pathway. Influenza a virus entry into cells lacking sialylated n.
Therefore, influenza virus has a substantial impact on health and the global economy. Pdf new influenza a virus entry inhibitors derived from. The section will also welcome the case reports of influenza outbreaks in both. Influenza virus entry and infection require host cell n. Request permission export citation add to favorites. These aspects of transmission are poorly understood due to a paucity of methods for quantifying infectious virus from airborne particles. With the risk of an influenza pandemic growing, it is increasingly important to understand virushost interactions in detail and to develop new antiviral strategies. Influenza a virus article about influenza a virus by the.
Influenza has haemagglutinins protruding from its viral envelope, which it uses to attach to host cells prior to entry. Influenza a viruses iavs cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective antiiav agents. These symptoms typically begin two days after exposure to the virus and most last less than a week. Influenza viruses replicate within the nucleus of the host cell. Preparedness and contingency plan for influenza pandemic of the ministry of health, pr china draft version the influenza abbreviation flu is the acute respiratory tract infectious disease caused by the flu virus. Hemagglutinin ha, the envelope glycoprotein of iav, plays a critical role in viral binding, fusion and entry. The two main viral players are the hemagglutinin and m2 proton channel. Influenza a virus hemagglutinin and neuraminidase act as. Influenza virus methods and protocols yohei yamauchi. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for antiinfluenza therapeutics development. Influenza b virus is almost exclusively a human pathogen, and is less common than influenza a. Competitive cooperation of hemagglutinin and neuraminidase. Influenza a virus iav enters host cells after attachment of its hemagglutinin ha to surfaceexposed sialic acid.
Lassa virus, which spreads from rodents to humans, infecting about half a million people every year, can lead to deadly hemorrhagic fever. Hcp influenza vaccination summary reporting in nhsn nhsn. Gal inhibited the infection of cells by influenza virus. This work is licensed under a creative commons attribution. Recently two of the more popular antiviral medications for fighting seasonal flu, amantadine and rimantadine, have been found to be ineffective against the 20052006 strain and have been pulled from the market new york times, 2006.
Influenza viruses are respiratory pathogens that represent a significant threat to public health, despite the largescale implementation of vaccination programs. One of the possible explanations is that the entry of influenza virus into the host cell employs a sialic acid independent mechanism, such as an alternative primary receptor molecule. Strains of all subtypes of influenza a virus have been isolated from wild birds, although disease is uncommon. Iav has a singlestranded, negativesense rna genome divided between eight subgenomic rna molecules. Influenza a virus iav membrane proteins hemagglutinin ha and neuraminidase na are determinants of virus infectivity, transmissibility, pathogenicity, host. Quercetin as an antiviral agent inhibits influenza a virus. Influenza a virus iav infection is mediated by attachment of the viral hemagglutinin to sialic acid on the host cell surface. Structure of ha the human influenza virus aaichi268 is the prototype of the h3 antigenic subtype viruses responsible for the pandemic of hong kong flu. Here we found that quercetin inhibited influenza infection with a. The discovery of neuraminidase inhibitors for the influenza virus is one of the early examples of structure based drug design.
Discovery of pentacyclic triterpenoids as potential entry. The clinical signs include chill, fever, malaise, myalgia, fatigue, headache, sore throat, cough, and stuffy or running nose. A large component of this antiviral program is regulated by the interferon family of signaling molecules. Viruses free fulltext microtubules in influenza virus entry and.
Structural biochemistryinfluenza virus wikibooks, open. Influenza a virus uses the aggresome processing machinery. Influenza causes significant loss of workdays, human suffering, and m. The world health assembly produced a resolution to try to address the crisis at its may 2007 meeting. For virus to successfully transmit through the air, it must be exhaled from an infected donor in sufficient quantities and retain infectiousness in the air. Virus entry is best understood in the case of viruses with a lipid envelope see first section of text, which introduce their genome into the cell by a fusion event between the viral and the cellular membrane. In addition, influenza virus infection results in structural changes in the microtubule network, which itself has consequences for viral replication. Influenza a virus iav is an enveloped virus of great medical impact. For enveloped viruses like influenza, the principal route of entry takes place by a combination of receptor binding and fusion. Evidence suggests that dandelion is associated with a.
To initiate infection, the virus first binds to cellularreceptors comprising either 2,3 or 2,6 linked sialic acid. Influenza virus has solved the problem of excessive genome size by dividing its genome into eight. Influenza a virus causes influenza in birds and some mammals, and is the only species of the genus alphainfluenzavirus of the virus family orthomyxoviridae. H7n9 avian influenza viruses are recent examples of animal viruses that acquired the. Influenza virus infection of lec1 cells is rescued by expression of gnt1. Influenza is a human respiratory infection caused by influenza viruses and spreads worldwide in an annual outbreak or occasionally in pandemics, resulting in significant morbidity and mortality herfst et al. By employing pseudovirusbased entry inhibition assays including h5n1 influenza a virus iav, and vsvg, the mechanism study indicated that the antiviral activity may be associated with the. The endosometrapped virus traffics via a unidirectional pathway to near the nucleus. Viruses free fulltext influenza a virus entry inhibitors targeting. For virus entry, hemagglutinin, the major glycoprotein on the surface of influenza virion, plays multiple roles in each step of the virus entry pathway. Despite the variation among viruses, there are several shared generalities concerning viral entry. This enzymes role is to free the progeny of the virus in order to spread and infect other cells within the body.
Some isolates of influenza a virus cause severe disease both in domestic poultry and, rarely, in humans. This requirement sheds light on the enigmatic resistance of bird cells. Influenza, commonly known as the flu, is an infectious disease of birds and mammals caused by an rna virus of the family orthomyxoviridae the influenza viruses. Chapters detail a broad range of methods from diagnosis, virus propagation, proteomics, haploid screening, lentiviral screening, virus entry, single molecule rna imaging, correlative light and electron microscopy clem, em, lightsheet microscopy, biochemistry, viral transcription, physiological infection models, animal models, in vivo imaging. As with all viruses, influenza virus needs to penetrate target cells to cause infection. Influenza, one of the most common infectious diseases, is a highly contagious airborne disease that occurs in seasonal epidemics and manifests as an acute febrile illness with variable degrees of systemic symptoms, ranging from mild fatigue to respiratory failure and death. In the case of influenza virus, these events have generally been well charac. Here, we seek to better understand how one of these antiviral. Whether fusion occurs by a lowphdependent or a phindependent. Ha binds sa through its receptorbinding sites, while na is a receptordestroying enzyme by removing sas. Entry of influenza virus into the host cell comprises.
Influenza, commonly known as the flu, is an infectious disease caused by an influenza virus. Preparedness and contingency plan for influenza pandemic. It is necessary to understand the detailed and complex interactions between influenza virus and its host cells in order to identify successful strategies for therapeutic intervention. Ifitm3 inhibits influenza a virus infection by preventing. These classifications are based on the distinct antigenic nature of the internal nucleoprotein and matrix proteins of each virus. Immunology and vaccinepreventable diseases pink book. After numerous entry studies with a variety of viruses in different cell systems, the overall picture of entry of. Onthe otherhand, hongkong, beingafree port andabusytourist centre, is also an effective place for virus exchange with.
Spanish influenza in 19181919 caused an estimated 21 million deaths worldwide. Therefore, ha is an attractive target for developing. Emerging antiviral strategies to interfere with influenza virus entry. Like many viruses, lassa virus binds to cell surface receptors. Influenza virus samples, international law, and global. The binding to sialic acid by ha may be a preentry step to attach the virus particle to the host cell surface. Author summary influenza epidemics exact a great toll on world health. In people, common symptoms of influenza are fever, sore throat, muscle pains, severe headache, coughing, and weakness and fatigue.
Human influenza is a seasonal disease associated with significant morbidity and mortality. Influenza diagnosis clinical and epidemiological characteristics increase of febrile respiratory illness lab isolation of influenza virus from clinical specimen e. Entry inhibitors are of particular importance in current efforts to develop a new generation of antiinfluenza virus drugs. In tcm, dandelion is a commonly used ingredient in many therapeutic remedies, either alone or in conjunction with other natural substances.
The primary event in influenza virus infection is the attachment of virus particles to the host cell surface, which is mediated by the binding of hemagglutinin ha. The first includes both influenza a and b viruses, while another is comprised of influenza c virus. To confirm that the inability of influenza virus to infect lec1 cells was solely due to the presence of terminal nlinked carbohydrate, we transiently expressed the wildtype gnt1 gene 17 in lec1 cells and examined virus infection. The evolution and epidemiology of influenza a virus iav infections in swine have been integrally tied to the segmented nature of the genome of the virus, which facilitates gene reassortment, and to the adaptability of these genes through mutation, which sometimes facilitates replication in a new host. The hemagglutinin ha and neuraminidase na of influenza a virus possess antagonistic activities on interaction with sialic acid sa, which is the receptor for virus attachment. Local residents are free to go to their native villages and return, provided they possess a reentry permit. The goal of a virus particle is to transport its genome in a replicationcompetent form from an infected cell to an uninfected cell. These substances form the basis of a haemagglutination assay, in which viral haemagglutinins bind and crosslink agglutinate red blood cells added to a test well, causing them to sink to the bottom of the solution as a mat. The only other animal known to be susceptible to influenza b infection is the seal.
The target of the influenza drug is based on the viruss neuraminidase enzyme. The two temperaturesensltlve ts lesions present in influenza ahong kong68ts 1e h3n268 virus were transferred via genetic reassortment to influenza ageorgia74 h3n274 wildtype virus. A widely held view of influenza virus infection is that the viral receptor consists of cell surface carbohydrate sialic acid, which can be present as glycoprotein or glycolipid. Antiflu traditional chinese medicine tcm has played a significant role in fighting the virus pandemic. To enter a new host cell, the majority of viruses take advantage of the endocytic mechanisms of the cell and wait until reaching endocytic vacuoles or other cytoplasmic compartments before penetrating into the cytosol. Avian influenza is a type of influenza a infection caused by avian bird influenza virus, type h5n1. Do i need to report hcp influenza vaccination summary data each month. The pentadecapeptides were identified through affinity selection from a phage. Acute respiratory diseases comprise over 75% of overall infectious disease occurrences in developed countries, of which 80% are caused by viruses. Thus, sialic acidmediated binding of virus to target cells is not required for virus entry, although the presence of sialic acid does increase the efficiency of virus infection. Here we report certain pentacyclic triterpenes exhibiting conserved structure features and with in vitro antiinfluenza virus activity comparable to and even higher than that of oseltamivir. Subsequently, the virus particles penetrated the vacuolar membranes and uncoating was observed within the cytoplasm without the intervention of lysosomal enzyme. This multivalent attachment by multiple copies of trimetric ha triggers endocytosis of influenza virus that is contained in the endosome. Entry of viruses such as sv40, echovirus 1 ev1, hiv1, measles virus, ebola virus and epsteinbarr virus ebv, can be enhanced by lipid microdomains, known as lipid rafts 4,5.
Viruses free fulltext microtubules in influenza virus. The function of ha during virus entry has been extensively investigated, however, examination of na has long. Pb1, and pa to constitute the biological active replicationtranscription units of influenza virus. Role for influenza virus envelope cholesterol in virus entry and infection. Pdf the influenza virus iv is still of great importance as it poses an immanent threat to humans and animals.
Abstract influenza a and b viruses are highly contagious respiratory. We demonstrate that pentadecapeptides that bind to a sialylgalactose structure neu5ac. Moreover, the virus causes outbreaks in poultry and other animals, such as pigs, requiring costly and laborious countermeasures. The influenza viruses section of virology journal will publish articles on all aspects of influenza virus research, including molecular genetics, molecular biology, biochemistry, biophysics, structural biology, cell biology, immunology, morphology, and pathogenesis.
I examine how the parties to this controversy used international law in framing and negotiating the dispute. Influenza virus entry and infection require host cell nlinked. Influenza a virus cell entry, replication, virion assembly and. The major steps involved in viral entry are shown below. We incubated the virions with various amounts of free cholesterol during the methyl. Like other viruses, influenza virus replicates in three main stages.
Author summary influenza viruses can transmit through the air between two hosts. However, influenza virus testing can inform clinical management when the results may influence. Lassa virus entry requires a triggerinduced receptor. Each of our cells contains antiviral factors that work to inhibit infection. The first pandemic of the 21st century occurred in 20092010. Influenza virus testing is not required to make a clinical diagnosis of influenza in outpatients with suspected influenza, particularly during increased influenza activity when seasonal influenza a and b viruses are circulating in the local community. Smith, andrewes, and laidlaw isolated influenza a virus in ferrets in 1933, and francis isolated influenza b virus in 1936.
424 1677 1311 632 1558 1020 1026 544 962 1053 700 1484 628 619 263 796 1116 351 523 468 613 1196 956 1180 573 1403 279 453 725 12 293 573 407