Detection of H275Y Mutation Conferring Oseltamivir Drug Resistance in Influenza A (H1N1) pdm09 Virus

In the treatment of influenza, Neuraminidase inhibitors (NAIs) (Oseltamivir and Zanamivir) play a major role. The emergence of variants of influenza A (H1N1) pdm09 virus resistant to Oseltamivir is a matter of great concern as it limits its usage. Therefore, vigilant monitoring for Oseltamivir-resistant viruses has been recommended by the World Health Organization (WHO). Our study aimed to screen the influenza A (H1N1) pdm09 virus for NAI drug resistance during the outbreak of 2015-16 in North-Western India. A total of 640 H1N1pdm09 virus-positive samples were screened for drug resistance to Oseltamivir by WHO allelic discrimination real-time RT-PCR protocol. The allelic discrimination PCR protocol can detect the presence of single nucleotide polymorphisms (SNPs), the H275Y mutation is detected by this method which causes resistance to Oseltamivir. Sanger sequencing of partial fragment of NA gene (fragment IV), of 90 samples were performed to confirm the presence of NA-H275Y mutation. Neuraminidase susceptibility of 20 randomly selected isolates to Oseltamivir was tested using NA inhibition chemiluminiscence based assay. Among 640 H1N1pdm09 positive samples tested, H275Y mutation was detected in one sample (0.15%) by PCR and confirmed by Sanger sequencing also. All the 20 isolates tested for NAI susceptibility by NA star assay were found to be sensitive to Oseltamivir. WHO allelic discrimination PCR is an easy, rapid and sensitive method for high-throughput detection of resistance to Oseltamivir. Systematic regular drug resistance surveillance of Influenza A is essential to monitor the emergence and spread of drug-resistant strains.

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

Genes ◽

10.3390/genes12121914 ◽

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.

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Frequency of oseltamivir resistance in Sydney, during the Newcastle outbreak of community transmitted oseltamivir-resistant influenza A(H1N1)pdm09 virus, Australia, June to August 2011

Eurosurveillance ◽

10.2807/ese.17.27.20210-en ◽

2012 ◽

Vol 17 (27) ◽

Cited By ~ 8

Author(s):

B Wang ◽

J Taylor ◽

M Ratnamohan ◽

K McPhie ◽

A Kesson ◽

...

Keyword(s):

Influenza A ◽

Convincing Evidence ◽

Post Treatment ◽

Antigenic Drift ◽

Oseltamivir Resistance ◽

Pdm09 Virus ◽

Influenza A H1n1 ◽

H275y Mutation ◽

Low Prevalence ◽

General Community

Although oseltamivir-resistant pandemic influenza A(H1N1)pdm09 is uncommon in immunocompetent individuals, a recent report from Newcastle, Australia, showed the first sustained community spread, from June to August 2011, of oseltamivir-resistant influenza A(H1N1)pdm09 virus carrying the H275Y neuraminidase (NA) mutation. To determine the frequency and the extent of this viral variant spread in the nearest major city to Newcastle, we performed a sequence-based genotypic assessment on samples from 143 oseltamivir untreated and 23 oseltamivir post-treatment individuals with influenza collected contemporaneously in Sydney, 120 km southwest of Newcastle. The detection of two of 143 (1.4%) community-derived samples containing H275Y suggests a low prevalence of oseltamivir-resistant influenza A(H1N1)pdm09 virus in the general community and no convincing evidence of spread of the NA H275Y-bearing influenza A(H1N1)pdm09 virus. In oseltamivir treated patients, oseltamivir-resistant influenza A(H1N1)pdm09 virus continue to emerge with three of 23 (13%) post-treatment samples containing the H275Y mutation. The observation of signature mutations and distinct phylogenetic relationship in full-length sequences of haemagglutinin and neuraminidase genes derived from 2011 strains against 2009 strains indicates continued genetic evolution and antigenic drift of the influenza A(H1N1)pdm09 viruses circulating in Australia.

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Progression and Trends in Virus from Influenza A to COVID-19: An Overview of Recent Studies

Viruses ◽

10.3390/v13061145 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1145

Author(s):

Hakimeh Baghaei Daemi ◽

Muhammad Fakhar-e-Alam Kulyar ◽

Xinlin He ◽

Chengfei Li ◽

Morteza Karimpour ◽

...

Keyword(s):

Influenza A ◽

H1n1 Virus ◽

World Health ◽

H1n1 Pandemic ◽

Global Pandemic ◽

First Case ◽

Influenza A H1n1 ◽

The World ◽

Novel Coronavirus ◽

Health Organization

Influenza is a highly known contagious viral infection that has been responsible for the death of many people in history with pandemics. These pandemics have been occurring every 10 to 30 years in the last century. The most recent global pandemic prior to COVID-19 was the 2009 influenza A (H1N1) pandemic. A decade ago, the H1N1 virus caused 12,500 deaths in just 19 months globally. Now, again, the world has been challenged with another pandemic. Since December 2019, the first case of a novel coronavirus (COVID-19) infection was detected in Wuhan. This infection has risen rapidly throughout the world; even the World Health Organization (WHO) announced COVID-19 as a worldwide emergency to ensure human health and public safety. This review article aims to discuss important issues relating to COVID-19, including clinical, epidemiological, and pathological features of COVID-19 and recent progress in diagnosis and treatment approaches for the COVID-19 infection. We also highlight key similarities and differences between COVID-19 and influenza A to ensure the theoretical and practical details of COVID-19.

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Seroprevalence study of infection with influenza A(H1N1)pdm09 virus in San Felipe Town, Chile

World Journal of Cardiovascular Diseases ◽

10.4236/wjcd.2013.37075 ◽

2013 ◽

Vol 03 (07) ◽

pp. 476-482

Author(s):

Olea Andrea ◽

Fasce Rodrigo ◽

Aguilera Ximena ◽

Oliva Otavio ◽

Muñoz Sergio ◽

...

Keyword(s):

Influenza A ◽

Seroprevalence Study ◽

Pdm09 Virus ◽

Influenza A H1n1

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Fluctuations in influenza-like illness epidemics and suicide mortality: A time-series regression of 13-year mortality data in South Korea

PLoS ONE ◽

10.1371/journal.pone.0244596 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0244596

Author(s):

Sun Jae Jung ◽

Sung-Shil Lim ◽

Jin-Ha Yoon

Keyword(s):

Time Series ◽

South Korea ◽

Influenza A ◽

Suicide Mortality ◽

Mortality Data ◽

Time Series Regression ◽

Influenza Like Illness ◽

Pdm09 Virus ◽

Influenza A H1n1 ◽

Novel Influenza A

Aims We explored the association between influenza epidemic and suicide mortality rates in a large population using a time-series regression of 13-year mortality data in South Korea. Methods Weekly suicide mortalities and influenza-like illness (ILI) were analyzed using time series regression. Regression coefficient for suicide mortality based on percentage change of ILI was calculated using a quasi-Poisson regression. Non-linear distributed lag models with quadratic function up to 24 weeks were constructed. Results The association between ILI and suicide mortality increased significantly up to 8 weeks post-influenza diagnosis. A significant positive association between ILI and suicide mortality was observed from 2009, when a novel influenza A(H1N1)pdm09 virus provoked a worldwide pandemic. No meaningful association between these factors was observed before 2009. Conclusion There was a significant positive relationship between ILI and suicide mortality after 2009, when a novel influenza A(H1N1)pdm09 virus provoked a worldwide pandemic.

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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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