scholarly journals Differential Host Determinants Contribute to the Pathogenesis of 2009 Pandemic H1N1 and Human H5N1 Influenza A Viruses in Experimental Mouse Models

2011 ◽  
Vol 179 (1) ◽  
pp. 230-239 ◽  
Author(s):  
Anna Otte ◽  
Martina Sauter ◽  
Lisa Alleva ◽  
Sigrid Baumgarte ◽  
Karin Klingel ◽  
...  
Keyword(s):  
Mouse Models ◽  
Influenza A ◽  
Pandemic H1n1 ◽  
Influenza A Viruses ◽  
Differential Host ◽  
Host Determinants ◽  
H5n1 Influenza ◽  
Experimental Mouse ◽  
Human H5n1

Evolutionary characterization of the six internal genes of H5N1 human influenza A virus

Microbiology ◽  
2000 ◽  
Vol 81 (5) ◽  
pp. 1293-1303 ◽  
Author(s):  
Yasuaki Hiromoto ◽  
Yoshinao Yamazaki ◽  
Tatsunobu Fukushima ◽  
Takehiko Saito ◽  
Stephen E. Lindstrom ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Phylogenetic Trees ◽  
Geographical Location ◽  
Amino Acid Sequences ◽  
Point Of View ◽  
Influenza A Viruses ◽  
Evolutionary Patterns ◽  
H5n1 Influenza ◽  
Human H5n1

The entire nucleotide sequences of all six internal genes of six human H5N1 influenza A viruses isolated in Hong Kong in 1997 were analysed in detail from a phylogenetic point of view and compared with the evolutionary patterns of the haemagglutinin and neuraminidase genes. Despite being isolated within a single year in the same geographical location, human H5N1 viruses were characterized by a variety of amino acid substitutions in the ribonucleoprotein complex [PB2, PB1, PA and nucleoprotein (NP)] as well as the matrix (M) proteins 1 and 2 and nonstructural (NS) proteins 1 and 2. The presence of previously reported amino acid sequences specific for human strains was confirmed in the PB2, PA, NP and M2 proteins. Nucleotide and amino acid sequence identities of the six internal genes of H5N1 viruses examined here were separated into at least two variant groups. In agreement with the above result, phylogenetic trees of the six internal genes of human H5N1 viruses were generally composed of two minor clades. Additionally, variable dendrogram topologies suggested that reassortment among viruses contributed further to the genetic variability of these viruses. As a result, it became clear that human H5N1 viruses are characterized by divergent gene constellations, suggesting the possible occurrence of genetic reassortment between viruses of the two evolutionary lineages.

scholarly journals Characterization of a Human H5N1 Influenza A Virus Isolated in 2003

2005 ◽  
Vol 79 (15) ◽  
pp. 9926-9932 ◽  
Author(s):  
Kyoko Shinya ◽  
Masato Hatta ◽  
Shinya Yamada ◽  
Ayato Takada ◽  
Shinji Watanabe ◽  
...  
Keyword(s):  
Hong Kong ◽  
Avian Influenza ◽  
Influenza A Virus ◽  
Influenza A ◽  
Mainland China ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
H5n1 Avian Influenza Virus ◽  
H5n1 Influenza ◽  
Avian Influenza A Virus

ABSTRACT In 2003, H5N1 avian influenza virus infections were diagnosed in two Hong Kong residents who had visited the Fujian province in mainland China, affording us the opportunity to characterize one of the viral isolates, A/Hong Kong/213/03 (HK213; H5N1). In contrast to H5N1 viruses isolated from humans during the 1997 outbreak in Hong Kong, HK213 retained several features of aquatic bird viruses, including the lack of a deletion in the neuraminidase stalk and the absence of additional oligosaccharide chains at the globular head of the hemagglutinin molecule. It demonstrated weak pathogenicity in mice and ferrets but caused lethal infection in chickens. The original isolate failed to produce disease in ducks but became more pathogenic after five passages. Taken together, these findings portray the HK213 isolate as an aquatic avian influenza A virus without the molecular changes associated with the replication of H5N1 avian viruses in land-based poultry such as chickens. This case challenges the view that adaptation to land-based poultry is a prerequisite for the replication of aquatic avian influenza A viruses in humans.

scholarly journals Molecular Characterization of the Hemagglutinin and Neuraminidase Genes of H5N1 Influenza A Viruses Isolated from Poultry in Vietnam from 2004 to 2005

2006 ◽  
Vol 68 (5) ◽  
pp. 527-531 ◽  
Author(s):  
Yukiko MURAMOTO ◽  
Thi Quynh Mai LE ◽  
Lien Song PHUONG ◽  
Tung NGUYEN ◽  
Thu Ha NGUYEN ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Influenza A ◽  
Influenza A Viruses ◽  
H5n1 Influenza

scholarly journals Influenza Antigens NP and M2 Confer Cross Protection to BALB/c Mice against Lethal Challenge with H1N1, Pandemic H1N1 or H5N1 Influenza A Viruses

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1708
Author(s):  
Nutan Mytle ◽  
Sonja Leyrer ◽  
Jon R. Inglefield ◽  
Andrea M. Harris ◽  
Thomas E. Hickey ◽  
...  
Keyword(s):  
Influenza A ◽  
Matrix Protein ◽  
Tandem Repeats ◽  
Protective Antigen ◽  
Serum Antibody ◽  
Cross Protection ◽  
Antigenic Drift ◽  
Natural Immunity ◽  
Pandemic H1n1 ◽  
H5n1 Influenza

Influenza hemagglutinin (HA) is considered a major protective antigen of seasonal influenza vaccine but antigenic drift of HA necessitates annual immunizations using new circulating HA versions. Low variation found within conserved non-HA influenza virus (INFV) antigens may maintain protection with less frequent immunizations. Conserved antigens of influenza A virus (INFV A) that can generate cross protection against multiple INFV strains were evaluated in BALB/c mice using modified Vaccinia virus Ankara (MVA)-vectored vaccines that expressed INFV A antigens hemagglutinin (HA), matrix protein 1 (M1), nucleoprotein (NP), matrix protein 2 (M2), repeats of the external portion of M2 (M2e) or as tandem repeats (METR), and M2e with transmembrane region and cytoplasmic loop (M2eTML). Protection by combinations of non-HA antigens was equivalent to that of subtype-matched HA. Combinations of NP and forms of M2e generated serum antibody responses and protected mice against lethal INFV A challenge using PR8, pandemic H1N1 A/Mexico/4108/2009 (pH1N1) or H5N1 A/Vietnam/1203/2004 (H5N1) viruses, as demonstrated by reduced lung viral burden and protection against weight loss. The highest levels of protection were obtained with NP and M2e antigens delivered as MVA inserts, resulting in broadly protective immunity in mice and enhancement of previous natural immunity to INFV A.

scholarly journals PB2 Residue 271 Plays a Key Role in Enhanced Polymerase Activity of Influenza A Viruses in Mammalian Host Cells

2010 ◽  
Vol 84 (9) ◽  
pp. 4395-4406 ◽  
Author(s):  
Kendra A. Bussey ◽  
Tatiana L. Bousse ◽  
Emily A. Desmet ◽  
Baek Kim ◽  
Toru Takimoto
Keyword(s):  
Mammalian Cells ◽  
Influenza A ◽  
Virus Titer ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Host Cells ◽  
Mammalian Host ◽  
Influenza A Viruses ◽  
H5n1 Influenza ◽  
Avian Viruses

ABSTRACT The direct infection of humans with highly pathogenic avian H5N1 influenza viruses has suggested viral mutation as one mechanism for the emergence of novel human influenza A viruses. Although the polymerase complex is known to be a key component in host adaptation, mutations that enhance the polymerase activity of avian viruses in mammalian hosts are not fully characterized. The genomic comparison of influenza A virus isolates has identified highly conserved residues in influenza proteins that are specific to either human or avian viruses, including 10 residues in PB2. We characterized the activity of avian polymerase complexes containing avian-to-human mutations at these conserved PB2 residues and found that, in addition to the E627K mutation, the PB2 mutation T271A enhances polymerase activity in human cells. We confirmed the effects of the T271A mutation using recombinant WSN viruses containing avian NP and polymerase genes with wild-type (WT) or mutant PB2. The 271A virus showed enhanced growth compared to that of the WT in mammalian cells in vitro. The 271A mutant did not increase viral pathogenicity significantly in mice compared to that of the 627K mutant, but it did enhance the lung virus titer. Also, cell infiltration was more evident in lungs of 271A-infected mice than in those of the WT. Interestingly, the avian-derived PB2 of the 2009 pandemic H1N1 influenza virus has 271A. The characterization of the polymerase activity of A/California/04/2009 (H1N1) and corresponding PB2 mutants indicates that the high polymerase activity of the pandemic strain in mammalian cells is, in part, dependent on 271A. Our results clearly indicate the contribution of PB2 amino acid 271 to enhanced polymerase activity and viral growth in mammalian hosts.

scholarly journals Virus persistence in pig herds led to successive reassortment events between swine and human influenza A viruses, resulting in the emergence of a novel triple-reassortant swine influenza virus

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Amélie Chastagner ◽  
Emilie Bonin ◽  
Christelle Fablet ◽  
Stéphane Quéguiner ◽  
Edouard Hirchaud ◽  
...  
Keyword(s):  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Infection Risk ◽  
Pandemic H1n1 ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Virus Persistence ◽  
Zoonotic Viruses ◽  
Swine Influenza A Virus

Abstract This report describes the detection of a triple reassortant swine influenza A virus of H1avN2 subtype. It evolved from an avian-like swine H1avN1 that first acquired the N2 segment from a seasonal H3N2, then the M segment from a 2009 pandemic H1N1, in two reassortments estimated to have occurred 10 years apart. This study illustrates how recurrent influenza infections increase the co-infection risk and facilitate evolutionary jumps by successive gene exchanges. It recalls the importance of appropriate biosecurity measures inside holdings to limit virus persistence and interspecies transmissions, which both contribute to the emergence of new potentially zoonotic viruses.

scholarly journals Protective Memory Responses Are Modulated by Priming Events prior to Challenge

2009 ◽  
Vol 84 (2) ◽  
pp. 1047-1056 ◽  
Author(s):  
John A. Rutigliano ◽  
Melissa Y. Morris ◽  
Wen Yue ◽  
Rachael Keating ◽  
Richard J. Webby ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A ◽  
T Cell Response ◽  
H3n2 Virus ◽  
Cell Mediated Immunity ◽  
Influenza A Viruses ◽  
Differential Survival ◽  
Virus Challenge ◽  
Response Characteristics ◽  
H5n1 Influenza

ABSTRACT Human infections with highly pathogenic H5N1 avian influenza A viruses in the last decade have legitimized fears of a long-predicted pandemic. We thus investigated the response to secondary infections with an engineered, but still highly virulent, H5N1 influenza A virus in the C57BL/6 mouse model. Mice primed with the H1N1 A/Puerto Rico/8/34 (PR8) virus were partially protected from lethality following respiratory infection with the modified H5N1 virus A/Vietnam/1203/04 (ΔVn1203). In contrast, those that had been comparably exposed to the HKx31 (H3N2) virus succumbed to the ΔVn1203 challenge, despite similarities in viral replication, weight loss, and secondary CD8+-T-cell response characteristics. All three viruses share the internal genes of PR8 that are known to stimulate protective CD8+-T-cell-mediated immunity. This differential survival of PR8- and HKx31-primed mice was also apparent for antibody-deficient mice challenged with the ΔVn1203 virus. The relative protection afforded by PR8 priming was abrogated in tumor necrosis factor-deficient (TNF−/−) mice, although lung fluids from the B6 HKx31-primed mice contained more TNF early after challenge. These data demonstrate that the nature of the primary infection can influence pathological outcomes following virulent influenza virus challenge, although the effect is not clearly correlated with classical measures of CD8+-T-cell-mediated immunity.

scholarly journals International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE

2015 ◽  
Vol 22 (8) ◽  
pp. 957-964 ◽  
Author(s):  
Karen L. Laurie ◽  
Othmar G. Engelhardt ◽  
John Wood ◽  
Alan Heath ◽  
Jacqueline M. Katz ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Incubation Time ◽  
Influenza A ◽  
Influenza Viruses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Influenza A Viruses ◽  
H5n1 Influenza ◽  
The World ◽  
International Laboratory ◽  
The Impact

ABSTRACTThe microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future.

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