Evolutionary, genetic, structural characterization and its functional implications for the influenza A (H1N1) infection outbreak in India from 2009 to 2017

Abstract Influenza A (H1N1) continues to be a major public health threat due to possible emergence of a more virulent H1N1 strain resulting from dynamic changes in virus adaptability consequent to functional mutations and antigenic drift in the hemagglutinin (HA) and neuraminidase (NA) surface proteins. In this study, we describe the genetic and evolutionary characteristics of H1N1 strains that circulated in India over a period of nine years from 2009 to 2017 in relation to global strains. The finding is important from a global perspective since previous phylogenetic studies have suggested that the tropics contributed substantially to the global circulation of influenza viruses. Bayesian phylogenic analysis of HA sequences along with global strains indicated that there is a temporal pattern of H1N1 evolution and clustering of Indian isolates with globally circulating strains. Interestingly, we observed four new amino acid substitutions (S179N, I233T, S181T and I312V) in the HA sequence of H1N1 strains isolated during 2017 and two (S181T and I312V) were found to be unique in Indian isolates. Structurally these two unique mutations could lead to altered glycan specificity of the HA gene. Similarly, sequence and structural analysis of NA domain revealed that the presence of K432E mutation in H1N1 strains isolated after 2015 from India and in global strains found to induce a major loop shift in the vicinity of the catalytic site. The findings presented here offer an insight as to how these acquired mutations could be associated to an improved adaptability of the virus for efficient human transmissibility.

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Molecular Characterization of Seasonal Influenza A and B from Hospitalized Patients in Thailand in 2018–2019

Viruses ◽

10.3390/v13060977 ◽

2021 ◽

Vol 13 (6) ◽

pp. 977

Author(s):

Kobporn Boonnak ◽

Chayasin Mansanguan ◽

Dennis Schuerch ◽

Usa Boonyuen ◽

Hatairat Lerdsamran ◽

...

Keyword(s):

Amino Acid ◽

Influenza A ◽

Seasonal Influenza ◽

Influenza Viruses ◽

Surface Proteins ◽

Antigenic Drift ◽

Influenza B ◽

Receptor Binding Site ◽

Antigenic Sites ◽

Ha Protein

Influenza viruses continue to be a major public health threat due to the possible emergence of more virulent influenza virus strains resulting from dynamic changes in virus adaptability, consequent of functional mutations and antigenic drift in surface proteins, especially hemagglutinin (HA) and neuraminidase (NA). In this study, we describe the genetic and evolutionary characteristics of H1N1, H3N2, and influenza B strains detected in severe cases of seasonal influenza in Thailand from 2018 to 2019. We genetically characterized seven A/H1N1 isolates, seven A/H3N2 isolates, and six influenza B isolates. Five of the seven A/H1N1 viruses were found to belong to clade 6B.1 and were antigenically similar to A/Switzerland/3330/2017 (H1N1), whereas two isolates belonged to clade 6B.1A1 and clustered with A/Brisbane/02/2018 (H1N1). Interestingly, we observed additional mutations at antigenic sites (S91R, S181T, T202I) as well as a unique mutation at a receptor binding site (S200P). Three-dimensional (3D) protein structure analysis of hemagglutinin protein reveals that this unique mutation may lead to the altered binding of the HA protein to a sialic acid receptor. A/H3N2 isolates were found to belong to clade 3C.2a2 and 3C.2a1b, clustering with A/Switzerland/8060/2017 (H3N2) and A/South Australia/34/2019 (H3N2), respectively. Amino acid sequence analysis revealed 10 mutations at antigenic sites including T144A/I, T151K, Q213R, S214P, T176K, D69N, Q277R, N137K, N187K, and E78K/G. All influenza B isolates in this study belong to the Victoria lineage. Five out of six isolates belong to clade 1A3-DEL, which relate closely to B/Washington/02/2009, with one isolate lacking the three amino acid deletion on the HA segment at position K162, N163, and D164. In comparison to the B/Colorado/06/2017, which is the representative of influenza B Victoria lineage vaccine strain, these substitutions include G129D, G133R, K136E, and V180R for HA protein. Importantly, the susceptibility to oseltamivir of influenza B isolates, but not A/H1N1 and A/H3N2 isolates, were reduced as assessed by the phenotypic assay. This study demonstrates the importance of monitoring genetic variation in influenza viruses regarding how acquired mutations could be associated with an improved adaptability for efficient transmission.

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Novel Swine Inﬂ uenza AH1N1 and the Phase Six Pandemic

Journal of Nepal Medical Association ◽

10.31729/jnma.100 ◽

2010 ◽

Vol 49 (179) ◽

Author(s):

M Khadka

Keyword(s):

Public Health ◽

Influenza A ◽

Swine Influenza ◽

Antigenic Drift ◽

World Health ◽

Health Concern ◽

Influenza A Viruses ◽

Influenza A H1n1 ◽

H1n1 Strain ◽

Health Organization

The family Orthomyxoviridae consists of Influenza A virus which is negative sense single stranded virus. The genome of the virus is segmented and possesses a peculiar trait of genetic reassortment. The influenza virus on its envelop consists of the antigenic glycoprotein like haemagglutinin (HA) and neuraminidase (NA). The changes in those glycoprotein components due to antigenic shift and antigenic drift leads to the development of new strain of Influenza A viruses. Now the novel swine influenza A/H1N1 strain has been detected from different parts of the world which is causing pandemic. World Health Organization has declared the pandemic phase six and more than 60 countries have reported the cases of novel influenza A/H1N1 strain including Nepal. As the disease is spreading world wide, it is a major public health concern for all the countries. And especially the developing countries like Nepal should immediately respond to the situation and should be well prepared to combat the disease before the disease spreads to enough population. Keywords: pandemic, public health, reassortment, swine influenza A/H1N1.

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Analysis of influenza A virus reinfection in children in Japan during 1983–91

Epidemiology and Infection ◽

10.1017/s0950268800058751 ◽

1995 ◽

Vol 115 (3) ◽

pp. 591-601 ◽

Cited By ~ 5

Author(s):

S. Nakajima ◽

F. Nishikawa ◽

K. Nakamura ◽

K. Nakajima

Keyword(s):

Amino Acid ◽

Influenza A Virus ◽

Influenza A ◽

Haemagglutination Inhibition ◽

Influenza Viruses ◽

Antigenic Drift ◽

H3n2 Virus ◽

Influenza B ◽

Influenza A H1n1 ◽

Influenza H3n2

SummaryThe epidemiology of influenza A in Japan was studied during 1979–91 and viruses isolated from reinfections during 1983–91 were analysed, Of 2963 influenza viruses isolated during this period, 922 and 1006 were influenza A(H1N1) and A(H3N2) viruses respectively; the others were influenza B viruses. Influenza A(H1N1) and A(H3N2) caused 5 and 6 epidemics respectively, most accompanied by antigenic drift. Seventeen reinfections with H1N1 and 17 with H3N2 were detected during our study. The primary and reinfection strains isolated from 7 H1N1 and 10 H3N2 cases were studied by haemagglutination-inhibition, and amino acid and nucleotide sequences of the HA1 region of the haemagglutinin. Most of the primary and reinfection strains were antigenically and genetically similar to the epidemic viruses circulating at that time. However, in 4 out of 10 cases of reinfection with influenza H3N2 virus, reinfection strains were genetically different from the epidemic viruses.

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Characterization of influenza A(H1N1)pdm09 viruses in Germany in season 2019-2020 – co-circulation of an antigenic drift variant

10.22541/au.162908014.49850019/v1 ◽

2021 ◽

Author(s):

Marianne Wedde ◽

Djin-Ye Oh ◽

Silke Buda ◽

Andrea Thürmer ◽

Sandra Kaiser ◽

...

Keyword(s):

Influenza A ◽

Influenza Season ◽

Vaccine Virus ◽

Influenza Viruses ◽

Antigenic Drift ◽

Neuraminidase Inhibitors ◽

Pdm09 Virus ◽

Time Period ◽

Influenza A H1n1

Background Influenza A(H1N1)pdm09 virus entered the human population in 2009 and evolved within this population for more than ten years. Despite genetic evolution no remarkable changes in the antigenic reactive pattern of these viruses were observed so far. Methods Primary respiratory samples of the German influenza virological sentinel were investigated by qPCR. Influenza virus-positive samples were characterized genetically and antigenetically. Results In December 2019, a antigenic drift variant characterized by an N156K substitution in the hemagglutinin of influenza A(H1N1)pdm09 virus emerged in Germany, which exhibited a reactivity to ferret antiserum that was an average 6 log2 lower than the vaccine virus A/Brisbane/02/2018 and the other A(H1N1)pdm09 viruses circulating in the influenza season 2019-2020. These viruses accounted for 20% of all A(H1N1)pdm09 viruses characterized in the German influenza sentinel. Patients infected with these viruses had a shorter median time period of medical consultation after onset of symptoms and were more frequently treated with neuraminidase inhibitors in comparison to patients infected with other A(H1N1)pdm09 viruses. Conclusions This parallel circulation of two antigenic variants of A(H1N1)pdm09 viruses which differ remarkably in their antigenic reactive pattern contributes to a greater variability in circulating influenza viruses and challenges vaccination.

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Antigenic and genetic diversity among swine influenza A H1N1 and H1N2 viruses in Europe

Journal of General Virology ◽

10.1099/0022-1317-83-4-735 ◽

2002 ◽

Vol 83 (4) ◽

pp. 735-745 ◽

Cited By ~ 83

Author(s):

S. Marozin ◽

V. Gregory ◽

K. Cameron ◽

M. Bennett ◽

M. Valette ◽

...

Keyword(s):

Genetic Diversity ◽

Influenza A ◽

Swine Influenza ◽

Influenza Viruses ◽

Antigenic Drift ◽

H3n2 Virus ◽

Human Populations ◽

Antigenic Variant ◽

Influenza A H1n1 ◽

The Uk

Three subtypes of influenza A viruses, H1N1, H1N2 and H3N2, co-evolve in pigs in Europe. H1N2 viruses isolated from pigs in France and Italy since 1997 were closely related to the H1N2 viruses which emerged in the UK in 1994. In particular, the close relationship of the neuraminidases (NAs) of these viruses to the NA of a previous UK H3N2 swine virus indicated that they had not acquired the NA from H3N2 swine viruses circulating in continental Europe. Moreover, antigenic and genetic heterogeneity among the H1N2 viruses appeared to be due in part to multiple introductions of viruses from the UK. On the other hand, comparisons of internal gene sequences indicated genetic exchange between the H1N2 viruses and co-circulating H1N1 and/or H3N2 subtypes. Most genes of the earlier (1997–1998) H1N2 isolates were more closely related to those of a contemporary French H1N1 isolate, whereas the genes of later (1999–2000) isolates, including the HAs of some H1N2 viruses, were closely related to those of a distinct H1N1 antigenic variant which emerged in France in 1999. In contrast, an H3N2 virus isolated in France in 1999 was closely related antigenically and genetically to contemporary human A/Sydney/5/97-like viruses. These studies reveal interesting parallels between genetic and antigenic drift of H1N1 viruses in pig and human populations, and provide further examples of the contribution of genetic reassortment to the antigenic and genetic diversity of swine influenza viruses and the importance of the complement of internal genes in the evolution of epizootic strains.

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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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Modeling and simulation of the spread of H1N1 flu with periodic vaccination

International Journal of Biomathematics ◽

10.1142/s1793524516500030 ◽

2015 ◽

Vol 09 (01) ◽

pp. 1650003 ◽

Cited By ~ 1

Author(s):

Islam A. Moneim

Keyword(s):

Influenza A ◽

Vaccination Strategy ◽

Vaccination Rate ◽

Influenza Viruses ◽

Sirs Epidemic Model ◽

Sirs Model ◽

Influenza A H1n1 ◽

Large Populations ◽

Stability Results ◽

Influenza H1n1

Influenza H1N1 has been found to exhibit oscillatory levels of incidence in large populations. Clear peaks for influenza H1N1 are observed in several countries including Vietnam each year [M. F. Boni, B. H. Manh, P. Q. Thai, J. Farrar, T. Hien, N. T. Hien, N. Van Kinh and P. Horby, Modelling the progression of pandemic influenza A (H1N1) in Vietnam and the opportunities for reassortment with other influenza viruses, BMC Med. 7 (2009) 43, Doi: 10.1186/1741-7015-7-43]. So it is important to study seasonal forces and factors which can affect the transmission of this disease. This paper studies an SIRS epidemic model with seasonal vaccination rate. This SIRS model has a unique disease-free solution (DFS). The value R0, the basic reproduction number is obtained when the vaccination is a periodic function. Stability results for the DFS are obtained when R0 < 1. The disease persists in the population and remains endemic if R0 > 1. Also when R0 > 1 existence of a nonzero periodic solution is proved. These results obtained for our model when the vaccination strategy is a non-constant time-dependent function.

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MOLECULAR AND GENETIC CHARACTERISTICS OF SURFACE AND NONSTRUCTURE PROTEINS OF PANDEMIC INFLUENZA VIRUSES A(H1N1)PDM09 IN 2015-2016 EPIDEMIC SEASON

Bulletin of Taras Shevchenko National University of Kyiv Series Biology ◽

10.17721/1728_2748.2016.72.44-48 ◽

2016 ◽

Vol 72 (2) ◽

pp. 44-48

Author(s):

O. Smutko ◽

L. Radchenko ◽

A. Mironenko

Keyword(s):

Amino Acid ◽

Pandemic Influenza ◽

Influenza A ◽

Phylogenetic Trees ◽

Influenza Viruses ◽

Amino Acid Substitutions ◽

Ns1 Protein ◽

Genetic Characteristics ◽

Epidemic Season ◽

Influenza A H1n1

The aim of the present study was identifying of molecular and genetic changes in hemaglutinin (HA), neuraminidase (NA) and non-structure protein (NS1) genes of pandemic influenza A(H1N1)pdm09 strains, that circulated in Ukraine during 2015-2016 epidemic season. Samples (nasopharyngeal swabs from patients) were analyzed using real-time polymerase chain reaction (RTPCR). Phylogenetic trees were constructed using MEGA 7 software. 3D structures were constructed in Chimera 1.11.2rc software. Viruses were collected in 2015-2016 season fell into genetic group 6B and in two emerging subgroups, 6B.1 and 6B.2 by gene of HA and NA. Subgroups 6B.1 and 6B.2 are defined by the following amino acid substitutions. In the NS1 protein were identified new amino acid substitutions D2E, N48S, and E125D in 2015-2016 epidemic season. Specific changes were observed in HA protein antigenic sites, but viruses saved similarity to vaccine strain. NS1 protein acquired substitution associated with increased virulence of the influenza virus.

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Cluster analysis of the origins of the new influenza A(H1N1) virus

Eurosurveillance ◽

10.2807/ese.14.21.19224-en ◽

2009 ◽

Vol 14 (21) ◽

Cited By ~ 14

Author(s):

A Solovyov ◽

G Palacios ◽

T Briese ◽

W I Lipkin ◽

R Rabadan

Keyword(s):

Cluster Analysis ◽

Influenza A ◽

H1n1 Virus ◽

Swine Influenza ◽

The United States ◽

Influenza Viruses ◽

World Health ◽

Influenza A H1n1 ◽

The World ◽

Health Organization

In March and April 2009, a new strain of influenza A(H1N1) virus has been isolated in Mexico and the United States. Since the initial reports more than 10,000 cases have been reported to the World Health Organization, all around the world. Several hundred isolates have already been sequenced and deposited in public databases. We have studied the genetics of the new strain and identified its closest relatives through a cluster analysis approach. We show that the new virus combines genetic information related to different swine influenza viruses. Segments PB2, PB1, PA, HA, NP and NS are related to swine H1N2 and H3N2 influenza viruses isolated in North America. Segments NA and M are related to swine influenza viruses isolated in Eurasia.

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Antigenic Drift of the Influenza A(H1N1)pdm09 Virus Neuraminidase Results in Reduced Effectiveness of A/California/7/2009 (H1N1pdm09)-Specific Antibodies

mBio ◽

10.1128/mbio.00307-19 ◽

2019 ◽

Vol 10 (2) ◽

Cited By ~ 18

Author(s):

Jin Gao ◽

Laura Couzens ◽

David F. Burke ◽

Hongquan Wan ◽

Patrick Wilson ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Influenza Viruses ◽

Antigenic Drift ◽

Influenza Vaccines ◽

Vaccine Production ◽

Antigenic Sites ◽

Vaccine Component ◽

Influenza A H1n1 ◽

The Impact

ABSTRACTThe effectiveness of influenza vaccines against circulating A(H1N1)pdm09 viruses was modest for several seasons despite the absence of antigenic drift of hemagglutinin (HA), the primary vaccine component. Since antibodies against HA and neuraminidase (NA) contribute independently to protection against disease, antigenic changes in NA may allow A(H1N1)pdm09 viruses to escape from vaccine-induced immunity. In this study, analysis of the specificities of human NA-specific monoclonal antibodies identified antigenic sites that have changed over time. The impact of these differences onin vitroinhibition of enzyme activity was not evident for polyclonal antisera until viruses emerged in 2013 without a predicted glycosylation site at amino acid 386 in NA. Phylogenetic and antigenic cartography demonstrated significant antigenic changes that in most cases aligned with genetic differences. Typical of NA drift, the antigenic difference is observed in one direction, with antibodies against conserved antigenic domains in A/California/7/2009 (CA/09) continuing to inhibit NA of recent A(H1N1)pdm09 viruses reasonably well. However, ferret CA/09-specific antiserum that inhibited the NA of A/Michigan/45/2015 (MI/15) very wellin vitro, protected mice against lethal MI/15 infection poorly. These data show that antiserum against the homologous antigen is most effective and suggest the antigenic properties of NA should not be overlooked when selecting viruses for vaccine production.IMPORTANCEThe effectiveness of seasonal influenza vaccines against circulating A(H1N1)pdm09 viruses has been modest in recent years, despite the absence of antigenic drift of HA, the primary vaccine component. Human monoclonal antibodies identified antigenic sites in NA that changed early after the new pandemic virus emerged. The reactivity of ferret antisera demonstrated antigenic drift of A(H1N1)pdm09 NA from 2013 onward. Passive transfer of serum raised against A/California/7/2009 was less effective than ferret serum against the homologous virus in protecting mice against a virus with the NA of more recent virus, A/Michigan/45/2015. Given the long-standing observation that NA-inhibiting antibodies are associated with resistance against disease in humans, these data demonstrate the importance of evaluating NA drift and suggest that vaccine effectiveness might be improved by selecting viruses for vaccine production that have NAs antigenically similar to those of circulating influenza viruses.

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