scholarly journals Next-Generation Sequencing Analysis of the Within-Host Genetic Diversity of Influenza A(H1N1)pdm09 Viruses in the Upper and Lower Respiratory Tracts of Patients with Severe Influenza

mSphere ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ikuyo Takayama ◽  
Binh Gia Nguyen ◽  
Co Xuan Dao ◽  
Thach The Pham ◽  
Tuan Quoc Dang ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Next Generation Sequencing ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Severe Disease ◽  
Pdm09 Virus ◽  
Influenza A H1n1 ◽  
Host Genetic ◽  
Ha Protein ◽  
Generation Sequencing

ABSTRACT The influenza A(H1N1)pdm09 virus emerged in April 2009 with an unusual incidence of severe disease and mortality, and currently circulates as a seasonal influenza virus. Previous studies using consensus viral genome sequencing data have overlooked the viral genomic and phenotypic diversity. Next-generation sequencing (NGS) may instead be used to characterize viral populations in an unbiased manner and to measure within-host genetic diversity. In this study, we used NGS analysis to investigate the within-host genetic diversity of influenza A(H1N1)pdm09 virus in the upper and lower respiratory samples from nine patients who were admitted to the intensive care unit (ICU). A total of 47 amino acid substitution positions were found to differ between the upper and lower respiratory tract samples from all patients. However, the D222G/N substitution in hemagglutinin (HA) protein was the only amino acid substitution common to multiple patients. Furthermore, the substitution was detected only in the six samples from the lower respiratory tract. Therefore, it is important to investigate influenza A(H1N1)pdm09 virus populations using multiple paired samples from the upper and lower respiratory tract to avoid overlooking potentially important substitutions, especially in patients with severe disease. IMPORTANCE The D222G/N substitution in the hemagglutinin (HA) protein of influenza A(H1N1)pdm09 virus has been reported to be associated with disease severity and mortality in numerous previous studies. In the present study, 75% of lower respiratory samples contained heterogeneous influenza populations that carried different amino acids at position 222 of the HA protein, whereas all upper respiratory samples only contained the wild-type 222D. These results suggest the influenza A(H1N1)pdm09 virus has diversified inside the host owing to differences in tissue specificity. In this study, the within-host genetic diversity of influenza A(H1N1)pdm09 virus was investigated for the first time using next-generation sequencing analysis of the viral whole-genome in samples extracted from the upper and lower respiratory tracts of patients with severe disease.

scholarly journals TNFA and IL10 Polymorphisms and IL-6 and IL-10 Levels Influence Disease Severity in Influenza A(H1N1)pdm09 Virus Infected Patients

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1914
Author(s):  
Kalichamy Alagarasu ◽  
Himanshu Kaushal ◽  
Pooja Shinde ◽  
Mahadeo Kakade ◽  
Urmila Chaudhary ◽  
...  
Keyword(s):  
Disease Severity ◽  
Influenza A ◽  
Severe Disease ◽  
Fatal Outcome ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mild Disease ◽  
Pdm09 Virus ◽  
Potential Biomarker ◽  
Influenza A H1n1

Cytokines are key modulators of immune response, and dysregulated production of proinflammatory and anti-inflammatory cytokines contributes to the pathogenesis of influenza A(H1N1)pdm09 virus infection. Cytokine production is impacted by single nucleotide polymorphisms (SNPs) in the genes coding for them. In the present study, SNPs in the IL6, TNFA, IFNG, IL17A, IL10, and TGFB were investigated for their association with disease severity and fatality in influenza A(H1N1)pdm09-affected patients with mild disease (n = 293) and severe disease (n = 86). Among those with severe disease, 41 patients had fatal outcomes. In a subset of the patients, levels of IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17 were assayed in the plasma for their association with severe disease. The frequency of TNFA rs1800629 G/A allele was significantly higher in severe cases and survived severe cases group compared to that of those with mild infection (OR with 95% for mild vs. severe cases 2.95 (1.52–5.73); mild vs. survived severe cases 4.02 (1.84–8.82)). IL10 rs1800896-rs1800872 G-C haplotype was significantly lower (OR with 95% 0.34 (0.12–0.95)), while IL10 rs1800896-rs1800872 G-A haplotype was significantly higher (OR with 95% 12.11 (2.23–76.96)) in fatal cases group compared to that of the mild group. IL-6 and IL-10 levels were significantly higher in fatal cases compared to that of survived severe cases. IL-6 levels had greater discriminatory power than IL-10 to predict progression to fatal outcome in influenza A(H1N1)pdm09 virus-infected patients. To conclude, the present study reports the association of TNFA and IL10 SNPs with severe disease in Influenza A(H1N1)pdm09 virus-infected subjects. Furthermore, IL-6 levels can be a potential biomarker for predicting fatal outcomes in Influenza A(H1N1)pdm09 virus infected subjects.

scholarly journals Analysis of intra-host genetic diversity of Prunus necrotic ringspot virus (PNRSV) using amplicon next generation sequencing

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0179284 ◽  
Author(s):  
Wycliff M. Kinoti ◽  
Fiona E. Constable ◽  
Narelle Nancarrow ◽  
Kim M. Plummer ◽  
Brendan Rodoni
Keyword(s):  
Genetic Diversity ◽  
Next Generation Sequencing ◽  
Ringspot Virus ◽  
Next Generation ◽  
Prunus Necrotic Ringspot Virus ◽  
Host Genetic ◽  
Generation Sequencing

scholarly journals Characterizing the Countrywide Epidemic Spread of Influenza A(H1N1)pdm09 Virus in Kenya between 2009 and 2018

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1956
Author(s):  
D. Collins Owuor ◽  
Zaydah R. de Laurent ◽  
Gilbert K. Kikwai ◽  
Lillian M. Mayieka ◽  
Melvin Ochieng ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Influenza A ◽  
Sequence Data ◽  
Influenza Viruses ◽  
Seasonal Fluctuations ◽  
Middle Income ◽  
Full Diversity ◽  
Virus Diversity ◽  
Pdm09 Virus ◽  
Influenza A H1n1

The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data are lacking. We isolated, sequenced, and analyzed 383 A(H1N1)pdm09 viral genomes from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods. The transmission dynamics of A(H1N1)pdm09 virus in Kenya were characterized by (i) multiple virus introductions into Kenya over the study period, although only a few of those introductions instigated local seasonal epidemics that then established local transmission clusters, (ii) persistence of transmission clusters over several epidemic seasons across the country, (iii) seasonal fluctuations in effective reproduction number (Re) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres, (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009–2011 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012–2017, and (v) virus spread across Kenya. Considerable influenza virus diversity circulated within Kenya, including persistent viral lineages that were unique to the country, which may have been capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle-income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions.

scholarly journals Monitoring Genetic Diversity of Influenza A(H1N1)pdm09 Virus Circulating during the Post-Pandemic Period in Turkey

2013 ◽  
Vol 66 (4) ◽  
pp. 299-305 ◽  
Author(s):  
Dilek Guldemir ◽  
Atila T. Kalaycioglu ◽  
A. Basak Altas ◽  
Gulay Korukluoglu ◽  
Riza Durmaz
Keyword(s):  
Genetic Diversity ◽  
Influenza A ◽  
Pdm09 Virus ◽  
Influenza A H1n1

scholarly journals Characterizing the countrywide epidemic spread of influenza A(H1N1)pdm09 virus in Kenya between 2009 and 2018

2021 ◽  
Author(s):  
D. Collins Owuor ◽  
Zaydah R. de Laurent ◽  
Gilbert K. Kikwai ◽  
Lillian M. Mayieka ◽  
Melvin Ochieng ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Influenza A ◽  
Sequence Data ◽  
Influenza Viruses ◽  
Seasonal Fluctuations ◽  
Middle Income ◽  
Virus Diversity ◽  
Pdm09 Virus ◽  
Geographical Regions ◽  
Influenza A H1n1

ABSTRACTBackgroundThe spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data is lacking.MethodsWe isolated, sequenced, and analyzed 383 influenza A(H1N1)pdm09 viral genomes isolated from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods.ResultsThe transmission dynamics of influenza A(H1N1)pdm09 virus in Kenya was characterized by: (i) multiple virus introductions into Kenya over the study period, although these were remarkably few, with only a few of those introductions instigating seasonal epidemics that then established local transmission clusters; (ii) persistence of transmission clusters over several epidemic seasons across the country; (iii) seasonal fluctuations in effective reproduction number (Re) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres; (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009-11 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012-17; and (v) virus migration from multiple geographical regions to multiple geographical destinations in Kenya.ConclusionConsiderable influenza virus diversity circulates within Africa, as demonstrated in this report, including virus lineages that are unique to the region, which may be capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions.

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