Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses

ABSTRACT To analyze the compatibility of avian influenza A virus hemagglutinins (HAs) and human influenza A virus matrix (M) proteins M1 and M2, we doubly infected Madin-Darby canine kidney cells with amantadine (1-aminoadamantane hydrochloride)-resistant human viruses and amantadine-sensitive avian strains. By using antisera against the human virus HAs and amantadine, we selected reassortants containing the human virus M gene and the avian virus HA gene. In our system, high virus yields and large, well-defined plaques indicated that the avian HAs and the human M gene products could cooperate effectively; low virus yields and small, turbid plaques indicated that cooperation was poor. The M gene products are among the primary components that determine the species specificities of influenza A viruses. Therefore, our system also indicated whether the avian HA genes effectively reassorted into the genome and replaced the HA gene of the prevailing human influenza A viruses. Most of the avian HAs that we tested efficiently cooperated with the M gene products of the early human A/PR/8/34 (H1N1) virus; however, the avian HAs did not effectively cooperate with the most recently isolated human virus that we tested, A/Nanchang/933/95 (H3N2). Cooperation between the avian HAs and the M proteins of the human A/Singapore/57 (H2N2) virus was moderate. These results suggest that the currently prevailing human influenza A viruses might have lost their ability to undergo antigenic shift and therefore are unable to form new pandemic viruses that contain an avian HA, a finding that is of great interest for pandemic planning.

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Serological epidemiological studies with influenza A viruses

Epidemiology and Infection ◽

10.1017/s0022172400045368 ◽

1965 ◽

Vol 63 (4) ◽

pp. 479-490 ◽

Cited By ~ 25

Author(s):

G. C. Schild ◽

C. H. Stuart-Harris

Keyword(s):

Older People ◽

Influenza A Virus ◽

Influenza A ◽

Age Distribution ◽

Epidemiological Studies ◽

Human Influenza ◽

Influenza A Viruses ◽

Swine Virus ◽

Human Sera ◽

Epidemiological Pattern

Determinations were made of the age distribution of antibody to swine virus and representatives of the various families of human influenza A virus in 1961–62 collections of human sera and paired sera from forty individuals taken in 1952 and 1963:(a) The existence of cohorts of the population, each with a dominant antibody type related to strains of virus first encountered in childhood, was confirmed.(b) The basic epidemiological pattern was similar to that previously detected in 1954. However, it seemed that antibody to swine virus had been reinforced but not antibody to A and A1 strains.(c) Neutralizing and HI antibodies to A/Equine/Miami/63 virus were detected only in the sera of older people (65 years or over) collected in 1964. No antibodies were found to A/Equine/Prague/56 or two duck viruses.(d) Relatively constant levels of antibody to A, A1 and A 2 viruses were present in sera from aged persons but antibody to swine virus diminished with age. This could be attributed to a lack of swine antibody in the older females.

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Long-term survival of influenza A viruses in aquatic invertebrate zoocultures

Veterinariya, Zootekhniya i Biotekhnologiya ◽

10.36871/vet.zoo.bio.202103005 ◽

2021 ◽

Vol 1 (3) ◽

pp. 34-41

Author(s):

S. L. Nesterchuk ◽

◽

V. A. Ostapenko ◽

Keyword(s):

Influenza Virus ◽

Daphnia Magna ◽

Influenza A Virus ◽

Influenza A ◽

The Body ◽

Aquatic Invertebrate ◽

Human Influenza ◽

Influenza A Viruses ◽

Term Survival ◽

Chicken Embryos

In experiments to infect aquatic invertebrates in the zooculture, we used influenza A viruses, namely, to infect crustaceans Daphnia magna Straus, 1826 – human influenza virus, Hong Kong strain 1569/79 (H3N2), and to infect molluscs Anodonta cygnea Linné, 1758 – influenza virus A birds, Strain Rostok 1/34 (Hav1Neq1) – the so-called true bird plague virus. As a result of a series of experiments, found that influenza A viruses persist in the water for no more than 3 days, while in the gills and mantle of molluscs the virus is isolated on chicken embryos for at least another 35 days after contact with virus-containing water (a total of 70 individuals were studied). From the body Daphnia magna, to isolate the human influenza A virus on chicken embryos was possible within 14 days after infection through water (examined 6,800 individuals), by the method of immunofluorescence the influenza virus was determined in the intestines of crustaceans during the entire period of observation – 70 days from the time of infection. Influenza A viruses do not have a harmful effect on crustaceans or molluscs, infected animals also develop and reproduce, as well as individuals of control groups. Interesting is the fact that we have established the possibility of the loss of agglutination of red blood cells of chickens as a result of the reproduction of the human influenza A virus in the body of invertebrate Daphnia magna, which indicates a change in the viral protein hemagglutinin. The use of aquatic invertebrate zooculture can help in the study of the circulation of influenza A viruses in nature, as well as in the study of the variability of influenza A viruses.

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Differential Recognition of Influenza A Viruses by M158–66Epitope-Specific CD8+T Cells Is Determined by Extraepitopic Amino Acid Residues

Journal of Virology ◽

10.1128/jvi.02439-15 ◽

2015 ◽

Vol 90 (2) ◽

pp. 1009-1022 ◽

Cited By ~ 15

Author(s):

Carolien E. van de Sandt ◽

Joost H. C. M. Kreijtz ◽

Martina M. Geelhoed-Mieras ◽

Nella J. Nieuwkoop ◽

Monique I. Spronken ◽

...

Keyword(s):

Amino Acid ◽

Influenza A Virus ◽

Influenza A ◽

Rational Design ◽

Amino Acid Residues ◽

Virus Infections ◽

Human Influenza ◽

Influenza A Viruses ◽

Specific Ctls ◽

Naturally Occurring

ABSTRACTNatural influenza A virus infections elicit both virus-specific antibody and CD4+and CD8+T cell responses. Influenza A virus-specific CD8+cytotoxic T lymphocytes (CTLs) contribute to clearance of influenza virus infections. Viral CTL epitopes can display variation, allowing influenza A viruses to evade recognition by epitope-specific CTLs. Due to functional constraints, some epitopes, like the immunodominant HLA-A*0201-restricted matrix protein 1 (M158–66) epitope, are highly conserved between influenza A viruses regardless of their subtype or host species of origin. We hypothesized that human influenza A viruses evade recognition of this epitope by impairing antigen processing and presentation by extraepitopic amino acid substitutions. Activation of specific T cells was used as an indication of antigen presentation. Here, we show that the M158–66epitope in the M1 protein derived from human influenza A virus was poorly recognized compared to the M1 protein derived from avian influenza A virus. Furthermore, we demonstrate that naturally occurring variations at extraepitopic amino acid residues affect CD8+T cell recognition of the M158–66epitope. These data indicate that human influenza A viruses can impair recognition by M158–66-specific CTLs while retaining the conserved amino acid sequence of the epitope, which may represent a yet-unknown immune evasion strategy for influenza A viruses. This difference in recognition may have implications for the viral replication kinetics in HLA-A*0201 individuals and spread of influenza A viruses in the human population. The findings may aid the rational design of universal influenza vaccines that aim at the induction of cross-reactive virus-specific CTL responses.IMPORTANCEInfluenza viruses are an important cause of acute respiratory tract infections. Natural influenza A virus infections elicit both humoral and cellular immunity. CD8+cytotoxic T lymphocytes (CTLs) are directed predominantly against conserved internal proteins and confer cross-protection, even against influenza A viruses of various subtypes. In some CTL epitopes, mutations occur that allow influenza A viruses to evade recognition by CTLs. However, the immunodominant HLA-A*0201-restricted M158–66epitope does not tolerate mutations without loss of viral fitness. Here, we describe naturally occurring variations in amino acid residues outside the M158–66epitope that influence the recognition of the epitope. These results provide novel insights into the epidemiology of influenza A viruses and their pathogenicity and may aid rational design of vaccines that aim at the induction of CTL responses.

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Inefficient Control of Host Gene Expression by the 2009 Pandemic H1N1 Influenza A Virus NS1 Protein

Journal of Virology ◽

10.1128/jvi.00081-10 ◽

2010 ◽

Vol 84 (14) ◽

pp. 6909-6922 ◽

Cited By ~ 112

Author(s):

Benjamin G. Hale ◽

John Steel ◽

Rafael A. Medina ◽

Balaji Manicassamy ◽

Jianqiang Ye ◽

...

Keyword(s):

Gene Expression ◽

Influenza A Virus ◽

Influenza A ◽

H1n1 Virus ◽

H1n1 Influenza ◽

Ns1 Protein ◽

Host Gene Expression ◽

Wild Type ◽

Influenza A Viruses ◽

2009 H1n1

ABSTRACT In 2009, a novel swine-origin H1N1 influenza A virus emerged. Here, we characterize the multifunctional NS1 protein of this human pandemic virus in order to understand factors that may contribute to replication efficiency or pathogenicity. Although the 2009 H1N1 virus NS1 protein (2009/NS1) is an effective interferon antagonist, we found that this NS1 (unlike those of previous human-adapted influenza A viruses) is unable to block general host gene expression in human or swine cells. This property could be restored in 2009/NS1 by replacing R108, E125, and G189 with residues corresponding to human virus consensus. Mechanistically, these previously undescribed mutations acted by increasing binding of 2009/NS1 to the cellular pre-mRNA processing protein CPSF30. A recombinant 2009 H1N1 influenza A virus (A/California/04/09) expressing NS1 with these gain-of-function substitutions was more efficient than the wild type at antagonizing host innate immune responses in primary human epithelial cells. However, such mutations had no significant effect on virus replication in either human or swine tissue culture substrates. Surprisingly, in a mouse model of pathogenicity, the mutant virus appeared to cause less morbidity, and was cleared faster, than the wild type. The mutant virus also demonstrated reduced titers in the upper respiratory tracts of ferrets; however, contact and aerosol transmissibility of the virus was unaffected. Our data highlight a potential human adaptation of NS1 that seems absent in “classically derived” swine-origin influenza A viruses, including the 2009 H1N1 virus. We discuss the impact that a natural future gain of this NS1 function may have on the new pandemic virus in humans.

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Sialic acid profiles in the respiratory tracts of selected species of raptors: evidence for potential binding sites for human and avian influenza A viruses

Wildlife Research ◽

10.1071/wr11003 ◽

2011 ◽

Vol 38 (8) ◽

pp. 647

Author(s):

Chun-Hua Han ◽

Jian Lin ◽

Xiuqing Wang ◽

Jing-Wen Han ◽

Hui-Juan Duan ◽

...

Keyword(s):

Sialic Acid ◽

Epithelial Cells ◽

Influenza A Virus ◽

Influenza A ◽

Human Influenza ◽

Influenza A Viruses ◽

Bubo Bubo ◽

Acid Receptor ◽

Influenza A Virus Infection ◽

Sialic Acid Receptor

Context The ability of influenza A viruses to recognise and bind to cell surface receptors such as sialic acid linked to galactose by an α2,3 linkage (SAα2,3-gal) and sialic acid linked to galactose by an α2,6 linkage (SAα2,6-gal) is a major determinant of influenza A virus infection. Although the epidemiological surveys of influenza A virus infection in raptors suggest that some raptor species are susceptible to influenza A viruses under natural conditions, the sialic acid profiles in the respiratory and intestinal tracts of raptors are unknown. Aims To examine the sialic acid receptor profiles in the respiratory tracts of the selected raptor species and assess the potential susceptibility of raptors to avian and human influenza viruses and the role of raptors in the epidemiology and evolution of influenza A viruses. Methods The lectin immunohistochemistry staining method was used to examine the sialic acid profiles in the respiratory tracts of eight different species of raptors. Key results A strong staining with Maackia amurensis agglutinin (MAA), specific for sialic acid linked to galactose by an α2,3 linkage (SAα2,3-gal), was observed in the epithelial cells of the respiratory tract of Accipiter nisus and Falco tinnunculus. However, a positive staining for both MAA and Sambucus nigra agglutinin (SNA), specific for sialic acid linked to galactose by an α2,6 linkage (SAα2,6-gal), was detected in the epithelial cells of the upper respiratory tract of Accipiter gularis, Buteo buteo, Otus sunia, Bubo bubo and Asio otus, and in the epithelial cells of the alveoli of Buteo buteo, Falco peregrinus, Otus sunia and Bubo bubo. Conclusions Both avian and human influenza A virus receptors are expressed in six species of raptors examined. There are some variations in the type and distribution of sialic acid receptor expression among different raptor species. No correlation between phylogeny of birds and their sialic acid receptor distributions was observed. Implications Since SAα2,3-gal and SAα2,6-gal are often considered as the primary receptors for avian influenza A viruses and human influenza A viruses, respectively, our data suggest that raptors could be a potential host for avian and human influenza A viruses.

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Multivalent Sialyllactose-Levan-Conjugated Gold Nanoparticles for Efficient Interaction with and Colorimetric Detection of Influenza A Virus

Chemosensors ◽

10.3390/chemosensors9070186 ◽

2021 ◽

Vol 9 (7) ◽

pp. 186

Author(s):

Sun-Jung Kim ◽

Pan Kee Bae ◽

Yong-Beom Shin

Keyword(s):

Gold Nanoparticles ◽

Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

Limit Of Detection ◽

Colorimetric Assay ◽

Colorimetric Detection ◽

H1n1 Influenza ◽

Human Influenza ◽

Human Influenza Virus

We report a colorimetric assay to detect influenza A virus using sialyllactose-levan-conjugated gold nanoparticles (AuNPs). We successfully conjugated 2, 3- and 2, 6-sialyllactose to levan and synthesized sialyllactose-levan-conjugated AuNPs. Each sialyllactose-conjugated levan specifically interacted with a recognizable lectin. Synthesized sialyllactose-conjugated levan acted as reducing and coating agents during the formation of AuNPs. Human influenza A virus specifically bound to 2, 6-sialyllactose-levan-conjugated AuNPs. Moreover, 2, 6-sialyllactose-conjugated levan AuNPs rapidly changed color from red to blue after incubation with human influenza virus. For detecting avian influenza virus, 2, 3-sialyllactose-levan-conjugated AuNPs were more effective than 2, 6-sialyllactose-levan-conjugated AuNPs. Therefore, the efficient targeting and diagnosis of influenza virus according to origin was possible. The deployment of sialyllactose-levan-conjugated particles for the detection of influenza virus is simple and quick. The limit of detection (L.O.D) of H1N1 influenza virus was 7.4 × 103 pfu using 2, 6-siallylactose-levan-conjugated AuNPs and H5N2 influenza virus was 4.2 × 103 pfu using 2, 3-siallylactose-levan- conjugated AuNPs.

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