scholarly journals Molecular Features of Highly Pathogenic Avian and Human H5N1 Influenza A Viruses in Asia

2012 ◽  
Vol 02 (02) ◽  
pp. 45-59 ◽  
Author(s):  
Wei Hu
Keyword(s):  
Influenza A ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Molecular Features ◽  
H5n1 Influenza ◽  
Human H5n1

H5N1 influenza A viruses from 2002 are highly pathogenic in waterfowl

2004 ◽  
Vol 1263 ◽  
pp. 200-204 ◽  
Author(s):  
Katharine M Sturm-Ramirez ◽  
Trevor Ellis ◽  
Barry Bousfield ◽  
Yi Guan ◽  
Malik Peiris ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
H5n1 Influenza

Single H5N1 influenza A neuraminidase mutation develops resistance to oseltamivir due to distorted conformational and drug binding landscape: multiple molecular dynamics analyses

RSC Advances ◽  
2015 ◽  
Vol 5 (14) ◽  
pp. 10849-10861 ◽  
Author(s):  
Ndumiso N. Mhlongo ◽  
Mahmoud E. S. Soliman
Keyword(s):  
Influenza A ◽  
Neuraminidase Inhibitor ◽  
Drug Binding ◽  
Single Mutation ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Dynamics Analyses ◽  
Orally Active ◽  
Pathogenic H5n1

Clinical studies showed that a single mutation, I117V, develops severe resistance to oseltamivir, the first orally active influenza A neuraminidase inhibitor, in highly pathogenic H5N1 influenza A viruses.

scholarly journals Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans between 2003 and 2008 in northern Vietnam

2010 ◽  
Vol 91 (10) ◽  
pp. 2485-2490 ◽  
Author(s):  
Q. M. Le ◽  
M. Ito ◽  
Y. Muramoto ◽  
P. V. M. Hoang ◽  
C. D. Vuong ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Northern Vietnam ◽  
H5n1 Influenza

scholarly journals Avian influenza: the role of the pig and public health implications

2017 ◽  
Vol 56 (4) ◽  
pp. 339
Author(s):  
C. S. KYRIAKIS (Κ. ΣΠ. ΚΥΡΙΑΚΗΣ) ◽  
K. Van REETH
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Influenza A ◽  
H5n1 Virus ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
H5n1 Influenza

The huge epizootics of highly pathogenic avian influenza (subtype H5N1) in Southeastern Asia over the last two years and especially the transmission of avian influenza viruses to humans have alerted the international scientific community. Many support that the threat of a new influenza pandemic appears greater today than ever before. During the 20th century, humanity has faced three pandemics, including the "Spanish flu" of 1918-19, which claimed over 20 to 40 million lives, and two less dramatic pandemics in 1957-58 and 1968-69. Influenza A viruses are single stranded RNA viruses belonging to the family Orthomyxoviridae. Their genome expresses only 10 proteins, most important of which are the two surface glycoproteins: haemagglutinin (HA) and neuraminidase (NA). So far, 16 different types of haemagglutinin (HI to Η16) and 9 of neuraminidase (Nl to N9) have been recognized. Influenza A viruses are grouped into "subtypes", according to the HA and NA surface proteins they bear (for example Η I N I , H5N2). Natural reservoirs of influenza A viruses are the wild aquatic birds (migratory waterfowl), from which all types of HA and NA have been isolated. It is important to mention that migratory waterfowl do not show clinical signs of disease, but shed the virus through their excretions.The host range of flu viruses includes domestic poultry, and mammalian species from aquatic mammals to horses, humans and swine. Because of their segmented single stranded RNA genome, influenza viruses have a very high mutation rate (genetic drift) and the possibility to undergo reassortment. Reassortment may occur when more than one virus co-infect the same cell, exchange genes and as a result, provide a totally new influenza virus (genetic shift). At least two subtypes of influenza A viruses are currendy endemic within the human population (H1N1 and H3N2), causing every year outbreaks of disease with very low mortality, especially in elders. Unlike these endemic viruses, pandemic viruses have a much higher morbidity, affecting people of all ages. Η I N I , H3N2 and H1N2 influenza viruses are currently circulating in the European and American swine population. Some of the swine influenza virus subtypes, namely Η I N I and H3N2, are thus similar to those of humans, but there are still important antigenic differences between them. Only rarely swine influenza viruses may be transmitted or cause disease to humans. Unlike mammalian influenza viruses, influenza viruses of domestic birds are grouped in two "pathotypes": low pathogenic avian influenza (LPAI) viruses, which cause localized infections and remain mild or subclinical, and highly pathogenic avian influenza (HPAI) viruses, which cause severe general infection with mortality up to 100% (fowl plague). The majority of avian influenza viruses are low pathogenic and only some, but not all, viruses of H5 and H7 subtypes are highly pathogenic. Occasionally low pathogenic Η5 or H7 viruses from wild birds transmit to poultry. Such viruses can undergo mutations in poultry as a result of which they may acquire a highly pathogenic phenotype. Until the recent avian influenza epizootics in Asia, the predominant theory for the creation of a pandemic virus supported that the pig was likely to act as an intermediate host for transmission of influenza viruses from birds to humans. The fact that genetic reassortment between human and avian viruses has also been shown to occur in pigs in nature, had led to the hypothesis that the pandemic viruses of 1957 and 1968 may have been generated through the pig. More recent data, however, come to question these theories and hypotheses: (a)the direct transmission of the H5N1 and H7N7 avian influenza viruses from birds to humans in Southeastern Asia and The Netherlands, and (b) the presence of cellular receptors recognized preferentially by the haemagglutinin of avian influenza viruses in the human conjunctiva and ciliated respiratory epithelial cells, which support that avian influenza viruses can be transmitted in toto (without reassortment) to and between humans or that humans can be the mixing vessel themselves. Furthermore, there is no solid scientific evidence to prove that any influenza virus reassortants, that have originated in swine, have posed a risk for humans. There are three criteria (conditions) an influenza virus must fulfill in order to be characterized as a pandemic virus: (a) it must be a new virus against which humans are immunologically naive, (b) it must be able to replicate in humans causing severe disease, and (c) it must be efficiendy transmitted among humans, causing wide outbreaks. So far the H5N1 influenza virus only fulfills the first and second condition, and even though it has been sporadically infecting humans for over two years, it has not yet been able to fully adapt to it's new host. Compared to the human population that may have been exposed to the H5N1 influenza virus in Asia, the number of patients and fatalities due to the H5N1 virus is very small. So far, it appears that swine do not play an important role in the epidemiology of this specific virus. Experimental infections of swine with highly pathogenic H5N1 virus have shown that it does not replicate extensively in pigs. Additionally, extensive serological investigations in the swine population of Viet Nam, indicated that the H5N1 virus merely spread to a very small number (~0.25%) of contact animals within the epizootic regions. Nevertheless, it is critical to continue monitor ring pigs and studying the behavior and spread of influenza viruses in these species.

scholarly journals Molecular Correlates of Influenza A H5N1 Virus Pathogenesis in Mice

2000 ◽  
Vol 74 (22) ◽  
pp. 10807-10810 ◽  
Author(s):  
Jacqueline M. Katz ◽  
Xiuhua Lu ◽  
Terrence M. Tumpey ◽  
Catherine B. Smith ◽  
Michael W. Shaw ◽  
...  
Keyword(s):  
Influenza A ◽  
H5n1 Virus ◽  
Highly Pathogenic Avian Influenza ◽  
Respiratory Illness ◽  
Influenza Viruses ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
H5n1 Influenza ◽  
Human H5n1 ◽  
Model Sequence

ABSTRACT Highly pathogenic avian influenza A H5N1 viruses caused an outbreak of human respiratory illness in Hong Kong. Of 15 human H5N1 isolates characterized, nine displayed a high-, five a low-, and one an intermediate-pathogenicity phenotype in the BALB/c mouse model. Sequence analysis determined that five specific amino acids in four proteins correlated with pathogenicity in mice. Alone or in combination, these specific residues are the likely determinants of virulence of human H5N1 influenza viruses in this model.

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 Plasticity of the Influenza Virus H5 HA Protein

mBio ◽  
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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