Adaptation of Pandemic H2N2 Influenza A Viruses in Humans

The 1957 A/H2N2 influenza virus caused an estimated 2 million fatalities during the pandemic. Since viruses of the H2 subtype continue to infect avian species and pigs, the threat of reintroduction into humans remains. To determine factors involved in the zoonotic origin of the 1957 pandemic, we performed analyses on genetic sequences of 175 newly sequenced human and avian H2N2 virus isolates and all publicly available influenza virus genomes.

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Sulphatide binds to human and animal influenza A viruses, and inhibits the viral infection

Biochemical Journal ◽

10.1042/bj3180389 ◽

1996 ◽

Vol 318 (2) ◽

pp. 389-393 ◽

Cited By ~ 57

Author(s):

Takashi SUZUKI ◽

Ayako SOMETANI ◽

Yasuhiro YAMAZAKI ◽

Goh HORIIKE ◽

Yukiko MIZUTANI ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

Sialic Acid Residue ◽

Influenza A Viruses ◽

Human Influenza Virus ◽

Viral Binding ◽

Overlay Assay ◽

Virus Isolates ◽

Darby Canine Kidney

We found, by using a virus overlay assay, that influenza A virus isolates bind to sulphatide (HSO3-Galβ1 → 1´Cer), which has no sialic acid residue, and that the infection of Madin–Darby canine kidney cells with the human influenza virus A/Memphis/1/71 (H3N2) is inhibited by sulphatide. A/Memphis/1/71 (H3N2) causes obvious haemagglutination and low-pH haemolysis of asialoerythrocytes reconstituted with sulphatide. All influenza A virus isolates from the species of animals so far tested bound to sulphatide. The sulphatide-binding specificity of the isolates was different from the viral sialyl-linkage specificity. Influenza A virus isolates also bound to galactosyl ceramide (GalCer; Galβ1 → 1´Cer), as well as sulphatide, in the virus overlay assays. In contrast, the influenza virus did not bind to N-deacyl, a derivative of sulphatide, glucosyl ceramide or the other neutral glycolipids tested. These results indicate that the linkage of galactose, or sulphated galactose, to ceramide is important for viral binding.

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Immunologic studies on the influenza A virus nonstructural protein NS1.

Journal of Experimental Medicine ◽

10.1084/jem.156.1.243 ◽

1982 ◽

Vol 156 (1) ◽

pp. 243-254 ◽

Cited By ~ 10

Author(s):

M W Shaw ◽

E W Lamon ◽

R W Compans

Keyword(s):

Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

Nonstructural Protein ◽

Antigenic Drift ◽

Ns1 Protein ◽

Influenza A Viruses ◽

Cytoplasmic Inclusions ◽

Infected Cells ◽

Virus Isolates

We purified the major influenza virus nonstructural protein, designated NS1, from cytoplasmic inclusions that were solubilized and used to raise antisera in rabbits. One of the antisera was found to be specific for NS1 by complement fixation tests and analyses of immune precipitates. Antiserum to NS1 isolated from cells infected with A/WSN/33 virus specifically precipitated NS1 from extracts of cells infected with seven distinct isolates of influenza A virus representing five different antigenic subtypes. These included A/WSN/33, A/PR/8/34, A/FW/5/50, A/USSR/90/77, A/RI/5+/57, A/Victoria/3/75, and A/Swine /1977/31; however, NS1 from cells infected with B/Lee/40 virus was not precipitated. Radioimmunoassays using radioiodinated NS1 protein from A/WSN virus-infected cells and unlabeled cytoplasmic extracts of cells infected with various strains of influenza virus as competitors indicated significant antigenic cross-reactivities for the NS1 proteins of all influenza A viruses tested. The results suggest a gradual antigenic drift over the 45 yr separating the earliest and most recent virus isolates examined. Thus, compared with the virion neuraminidase and hemagglutinin antigens, NS1 appears to be highly conserved in different influenza A virus isolates.

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Serological and virological surveys of the influenza A viruses in Antarctic and sub-Antarctic penguins

Antarctic Science ◽

10.1017/s0954102012001228 ◽

2013 ◽

Vol 25 (2) ◽

pp. 339-344 ◽

Cited By ~ 12

Author(s):

F. Xavier Abad ◽

Núria Busquets ◽

Azucena Sanchez ◽

Peter G. Ryan ◽

Natàlia Majó ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A ◽

Enzyme Linked Immunosorbent Assay ◽

Influenza A Viruses ◽

Serum Samples ◽

Livingston Island ◽

Polymerase Chain ◽

Virus Genomes ◽

Precise Role ◽

Penguin Species

AbstractTo evaluate the avian influenza virus (AIV) circulation in Antarctic and sub-Antarctic penguins we carried out a serosurvey on six species from Livingston, Marion and Gough islands. Seropositivity against AIV was performed on serum samples using a competitive enzyme-linked immunosorbent assay and haemagglutination and neuraminidase inhibition assays. Some oropharyngeal and cloacal swabs were also assayed to detect influenza virus genomes by real time reverse transcription-polymerase chain reaction. Overall, 12.1% (n= 140) penguins were seropositive to AIV. By species, we detected 5% (n= 19) and 11% (n= 18) seroprevalence in sub-Antarctic rockhopper penguins (Eudyptesspp.) from Gough and Marion islands, respectively, 42% (n= 33) seroprevalence in macaroni penguins (Eudyptes chysolophusBrandt), but no positives in the three other species, gentoo (Pygoscelis papuaForster;n= 25) and chinstrap penguins (P. antarcticaForster;n= 16), from Livingston Island and king penguins (Aptenodytes patagonicusMiller;n= 27) from Marion Island. While seropositivity reflected previous exposure to the AIV, the influenza genome was not detected. Our results indicate that AIV strains have circulated in penguin species in the sub-Antarctic region, but further studies are necessary to determine the precise role that such penguin species play in AIV epidemiology and if this circulation is species (or genus) specific.

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Chimeric Hemagglutinin-Based Live-Attenuated Vaccines Confer Durable Protective Immunity against Influenza A Viruses in a Preclinical Ferret Model

Vaccines ◽

10.3390/vaccines9010040 ◽

2021 ◽

Vol 9 (1) ◽

pp. 40

Author(s):

Wen-Chun Liu ◽

Raffael Nachbagauer ◽

Daniel Stadlbauer ◽

Shirin Strohmeier ◽

Alicia Solórzano ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A ◽

Influenza Virus Infection ◽

Influenza Virus Vaccine ◽

Antibody Responses ◽

Upper Respiratory Tract ◽

Influenza A Viruses ◽

Humoral And Cellular Immunity ◽

Stalk Domain ◽

One Year

Epidemic or pandemic influenza can annually cause significant morbidity and mortality in humans. We developed novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccines, which contain a conserved HA stalk domain from a 2009 pandemic H1N1 (pH1N1) strain combined with globular head domains from avian influenza A viruses. Our previous reports demonstrated that prime-boost sequential immunizations induced robust antibody responses directed toward the conserved HA stalk domain in ferrets. Herein, we further followed vaccinated animals for one year to compare the efficacy and durability of these vaccines in the preclinical ferret model of influenza. Although all cHA-based immunization regimens induced durable HA stalk-specific and heterosubtypic antibody responses in ferrets, sequential immunization with live-attenuated influenza virus vaccines (LAIV-LAIV) conferred the best protection against upper respiratory tract infection by a pH1N1 influenza A virus. The findings from this study suggest that our sequential immunization strategy for a cHA-based universal influenza virus vaccine provides durable protective humoral and cellular immunity against influenza virus infection.

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Influenza: An Emerging and Re-emerging Public Health Threat in Nepal

Annals of Clinical Chemistry and Laboratory Medicine ◽

10.3126/acclm.v3i2.20737 ◽

2018 ◽

Vol 3 (2) ◽

pp. 1-2

Author(s):

Bishnu Prasad Upadhyay

Keyword(s):

Influenza Virus ◽

Influenza A ◽

Winter Season ◽

Emerging Infectious Diseases ◽

Influenza Viruses ◽

Influenza B ◽

Influenza A Viruses ◽

Influenza A H1n1 ◽

New Variant ◽

Seasonal Epidemics

Influenza virus type A and B are responsible for seasonal epidemics as well as pandemics in human. Influenza A viruses are further divided into two major groups namely, low pathogenic seasonal influenza (A/H1N1, A/H1N1 pdm09, A/H3N2) and highly pathogenic influenza virus (H5N1, H5N6, H7N9) on the basis of two surface antigens: hemagglutinin (HA) and neuraminidase (NA). Mutations, including substitutions, deletions, and insertions, are one of the most important mechanisms for producing new variant of influenza viruses. During the last 30 years; more than 50 viral threat has been evolved in South-East Asian countriesof them influenza is one of the major emerging and re-emerging infectious diseases of global concern. Similar to tropical and sub-tropical countries of Southeast Asia; circulation of A/H1N1 pdm09, A/H3N2 and influenza B has been circulating throughout the year with the peak during July-November in Nepal. However; the rate of infection transmission reach peak during the post-rain and winter season of Nepal.

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Characterization of H9N2 influenza A viruses isolated from chicken products imported into Japan from China

Epidemiology and Infection ◽

10.1017/s0950268806006728 ◽

2006 ◽

Vol 135 (3) ◽

pp. 386-391 ◽

Cited By ~ 13

Author(s):

M. MASE ◽

M. ETO ◽

K. IMAI ◽

K. TSUKAMOTO ◽

S. YAMAGUCHI

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Influenza A ◽

H9n2 Virus ◽

Amino Acid Substitutions ◽

Influenza A Viruses ◽

Potential Sources

We characterized eleven H9N2 influenza A viruses isolated from chicken products imported from China. Genetically they were classified into six distinct genotypes, including five already known genotypes and one novel genotype. This suggested that such multiple genotypes of the H9N2 virus have possibly already become widespread and endemic in China. Two isolates have amino-acid substitutions that confer resistance to amantadine in the M2 region, and this supported the evidence that this mutation might be a result of the wide application of amantadine for avian influenza treatment in China. These findings emphasize the importance of surveillance for avian influenza virus in this region, and of quarantining imported chicken products as potential sources for the introduction of influenza virus.

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Plasticity of the Influenza Virus H5 HA Protein

mBio ◽

10.1128/mbio.03324-20 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Huihui Kong ◽

David F. Burke ◽

Tiago Jose da Silva Lopes ◽

Kosuke Takada ◽

Masaki Imai ◽

...

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Mammalian Cells ◽

Influenza A ◽

Viral Antigen ◽

Influenza Viruses ◽

Influenza A Viruses ◽

Highly Pathogenic ◽

Antigenic Properties ◽

Ha Protein

ABSTRACT Since the emergence of highly pathogenic avian influenza viruses of the H5 subtype, the major viral antigen, hemagglutinin (HA), has undergone constant evolution, resulting in numerous genetic and antigenic (sub)clades. To explore the consequences of amino acid changes at sites that may affect the antigenicity of H5 viruses, we simultaneously mutated 17 amino acid positions of an H5 HA by using a synthetic gene library that, theoretically, encodes all combinations of the 20 amino acids at the 17 positions. All 251 mutant viruses sequenced possessed ≥13 amino acid substitutions in HA, demonstrating that the targeted sites can accommodate a substantial number of mutations. Selection with ferret sera raised against H5 viruses of different clades resulted in the isolation of 39 genotypes. Further analysis of seven variants demonstrated that they were antigenically different from the parental virus and replicated efficiently in mammalian cells. Our data demonstrate the substantial plasticity of the influenza virus H5 HA protein, which may lead to novel antigenic variants. IMPORTANCE The HA protein of influenza A viruses is the major viral antigen. In this study, we simultaneously introduced mutations at 17 amino acid positions of an H5 HA expected to affect antigenicity. Viruses with ≥13 amino acid changes in HA were viable, and some had altered antigenic properties. H5 HA can therefore accommodate many mutations in regions that affect antigenicity. The substantial plasticity of H5 HA may facilitate the emergence of novel antigenic variants.

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Evaluating the fitness of PA/I38T-substituted influenza A viruses with reduced baloxavir susceptibility in a competitive mixtures ferret model

10.1101/2020.09.28.316620 ◽

2020 ◽

Author(s):

Leo YY Lee ◽

Jie Zhou ◽

Paulina Koszalka ◽

Rebecca Frise ◽

Rubaiyea Farrukee ◽

...

Keyword(s):

Influenza A ◽

Relative Fitness ◽

Replication Capacity ◽

Wild Type ◽

Influenza A Viruses ◽

Widespread Occurrence ◽

Host Fitness ◽

Recombinant Viruses ◽

Risk Patients ◽

Virus Isolates

AbstractBaloxavir is approved in several countries for the treatment of uncomplicated influenza in otherwise-healthy and high-risk patients. Treatment-emergent viruses with reduced susceptibility to baloxavir have been detected in clinical trials, but the likelihood of widespread occurrence depends on replication capacity and onward transmission. We evaluated the fitness of A/H3N2 and A/H1N1pdm09 viruses with the polymerase acidic I38T-variant conferring reduced susceptibility to baloxavir relative to wild-type (WT) viruses, using a competitive mixture ferret model, recombinant viruses and patient-derived virus isolates. The A/H3N2 I38T virus showed a reduction in within-host fitness but comparable between-host fitness to the WT virus, while the A/H1N1pdm09 I38T virus had broadly similar within-host fitness but substantially lower between-host fitness. Although I38T viruses replicate and transmit between ferrets, our data suggest that viruses with this amino acid substitution have lower fitness relative to WT and this relative fitness cost was greater in A/H1N1pdm09 viruses than in A/H3N2 viruses.

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Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Preimmune to Seasonal Influenza A Viruses

mSphere ◽

10.1128/msphere.00052-21 ◽

2021 ◽

Vol 6 (2) ◽

Author(s):

Z. Beau Reneer ◽

Amanda L. Skarlupka ◽

Parker J. Jamieson ◽

Ted M. Ross

Keyword(s):

Influenza Virus ◽

Immune Responses ◽

Recombinant Proteins ◽

Human Population ◽

Influenza A ◽

Seasonal Influenza ◽

Influenza Viruses ◽

Wild Type ◽

Influenza A Viruses ◽

Global Pandemic

ABSTRACT Influenza vaccines have traditionally been tested in naive mice and ferrets. However, humans are first exposed to influenza viruses within the first few years of their lives. Therefore, there is a pressing need to test influenza virus vaccines in animal models that have been previously exposed to influenza viruses before being vaccinated. In this study, previously described H2 computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) vaccines (Z1 and Z5) were tested in influenza virus “preimmune” ferret models. Ferrets were infected with historical, seasonal influenza viruses to establish preimmunity. These preimmune ferrets were then vaccinated with either COBRA H2 HA recombinant proteins or wild-type H2 HA recombinant proteins in a prime-boost regimen. A set of naive preimmune or nonpreimmune ferrets were also vaccinated to control for the effects of the multiple different preimmunities. All of the ferrets were then challenged with a swine H2N3 influenza virus. Ferrets with preexisting immune responses influenced recombinant H2 HA-elicited antibodies following vaccination, as measured by hemagglutination inhibition (HAI) and classical neutralization assays. Having both H3N2 and H1N1 immunological memory regardless of the order of exposure significantly decreased viral nasal wash titers and completely protected all ferrets from both morbidity and mortality, including the mock-vaccinated ferrets in the group. While the vast majority of the preimmune ferrets were protected from both morbidity and mortality across all of the different preimmunities, the Z1 COBRA HA-vaccinated ferrets had significantly higher antibody titers and recognized the highest number of H2 influenza viruses in a classical neutralization assay compared to the other H2 HA vaccines. IMPORTANCE H1N1 and H3N2 influenza viruses have cocirculated in the human population since 1977. Nearly every human alive today has antibodies and memory B and T cells against these two subtypes of influenza viruses. H2N2 influenza viruses caused the 1957 global pandemic and people born after 1968 have never been exposed to H2 influenza viruses. It is quite likely that a future H2 influenza virus could transmit within the human population and start a new global pandemic, since the majority of people alive today are immunologically naive to viruses of this subtype. Therefore, an effective vaccine for H2 influenza viruses should be tested in an animal model with previous exposure to influenza viruses that have circulated in humans. Ferrets were infected with historical influenza A viruses to more accurately mimic the immune responses in people who have preexisting immune responses to seasonal influenza viruses. In this study, preimmune ferrets were vaccinated with wild-type (WT) and COBRA H2 recombinant HA proteins in order to examine the effects that preexisting immunity to seasonal human influenza viruses have on the elicitation of broadly cross-reactive antibodies from heterologous vaccination.

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Large-Scale Sequence Analysis of M Gene of Influenza A Viruses from Different Species: Mechanisms for Emergence and Spread of Amantadine Resistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00650-09 ◽

2009 ◽

Vol 53 (10) ◽

pp. 4457-4463 ◽

Cited By ~ 64

Author(s):

Yuki Furuse ◽

Akira Suzuki ◽

Hitoshi Oshitani

Keyword(s):

Influenza Virus ◽

Influenza A ◽

Drug Resistant ◽

Human Influenza ◽

Influenza A Viruses ◽

M Gene ◽

Drug Pressure ◽

Human Influenza Virus ◽

Selective Pressures ◽

Amantadine Resistance

ABSTRACT Influenza A virus infects many species, and amantadine is used as an antiviral agent. Recently, a substantial increase in amantadine-resistant strains has been reported, most of which have a substitution at amino acid position 31 in the M2 gene. Understanding the mechanism responsible for the emergence and spread of antiviral resistance is important for developing a treatment protocol for seasonal influenza and for deciding on a policy for antiviral stockpiling for pandemic influenza. The present study was conducted to identify the existence of drug pressure on the emergence and spread of amantadine-resistant influenza A viruses. We analyzed data on more than 5,000 virus sequences and constructed a phylogenetic tree to calculate selective pressures on sites in the M2 gene associated with amantadine resistance (positions 26, 27, 30, and 31) among different hosts. The phylogenetic tree revealed that the emergence and spread of the drug-resistant M gene in different hosts and subtypes were independent and not through reassortment. For human influenza virus, positive selection was detected only at position 27. Selective pressures on the sites were not always higher for human influenza virus than for viruses of other hosts. Additionally, selective pressure on position 31 did not increase after the introduction of amantadine. Although there is a possibility of drug pressure on human influenza virus, we could not find positive pressure on position 31. Because the recent rapid increase in drug-resistant virus is associated with the substitution at position 31, the resistance may not be related to drug use.

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