Selenium Nanoparticles Inhibited H1N1 Influenza Virus Induced Apoptosis By Improving The Level of Gpx1

Abstract Influenza A (H1N1) viruses are distributed around the world and pose a threat to public health. Vaccination is the main treatment strategy to prevent influenza infection, but antiviral drugs also play an important role in controlling seasonal and pandemic influenza. Currently, influenza viruses may emerge antiviral resistance, new agents with different modes of action are being investigated. Recently, selenium nanoparticles (SeNPs) which have antiviral effects attracted more and more attention in biomedical interventions. The appearance of nanotechnology attract great attention in the nanomedicine field. SeNPs constitute an attractive vector platform for delivering a variety of drugs to action targets. SeNPs is being explored for potential therapeutic efficacy in a variety of oxidative stress and inflammation-mediated diseases, such as cancer, arthritis, diabetes, and kidney disease. SeNPs could inhibit infection of Madin Darby Canine Kidney (MDCK) cells with H1N1 and prevent chromatin condensation and DNA fragmentation. ROS play a key role in physiological processes on apoptosis. SeNPs significantly inhibited the production of reactive oxygen species (ROS) in MDCK cells. Mechanistic investigation revealed that SeNPs inhibited the apoptosis induced by H1N1 virus infection in MDCK cells by improving the level of GPx1. Our results suggest that SeNPs is an effective selenium source to obtain H1N1 influenza antiviral candidate.

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The Inhibition of H1N1 influenza virus-induced apoptosis by functionalized Selenium nanoparticles with β-Thujaplicin through ROS-mediated P53 and AKT signaling pathways

10.21203/rs.3.rs-15986/v1 ◽

2020 ◽

Author(s):

Changbing Wang ◽

Mingqi Zhao ◽

Zhengfang Lin ◽

Min Guo ◽

Tiantian Xu ◽

...

Keyword(s):

Influenza Virus ◽

Signaling Pathways ◽

Mdck Cells ◽

Biological Activities ◽

Chromatin Condensation ◽

H1n1 Influenza ◽

Selenium Nanoparticles ◽

H1n1 Influenza Virus ◽

Biomedical Intervention ◽

Mechanistic Investigation

Abstract β-Thujaplicin possess a variety of biological activities. The use of modified biological nanoparticles (NPs) to develop novel anti-influenza drugs has increased in recent years. Selenium nanoparticles (SeNPs) with antiviral has attracted increasing attention for biomedical intervention. Functionalized SeNPs by β-Thujaplicin (Se@TP) surface modified with superior antiviral were synthesized in this study. β-Thujaplicin decoration of SeNPs obviously inhibited H1N1 infection and were less toxicity. Se@TP could inhibit H1N1 from infecting Madin Darby Canine Kidney (MDCK) cells and block chromatin condensation and DNA fragmentation. Se@TP obviously prevented MDCK cells from generating reactive oxygen species (ROS). Furthermore, Se@TP prevent lung injury in H1N1 infected mice through eosin staining and hematoxylin in vivo . Additionally, when treated with Se@TP, the DNA damage of lung tissues reduced substantially by TUNEL-DAPI test. Mechanistic investigation revealed that Se@TP inhibited H1N1 influenza virus from infecting MDCK cells through induction of apoptosis via suppression AKT and p53 signaling pathways through Immunohistochemical assay. Our results suggest that β-Thujaplicin modified SeNPs as carriers is an efficient way to achieve antiviral pharmaceutical candidate for H1N1 influenza.

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Contemporary Seasonal Influenza A (H1N1) Virus Infection Primes for a More Robust Response To Split Inactivated Pandemic Influenza A (H1N1) Virus Vaccination in Ferrets

Clinical and Vaccine Immunology ◽

10.1128/cvi.00247-10 ◽

2010 ◽

Vol 17 (12) ◽

pp. 1998-2006 ◽

Cited By ~ 11

Author(s):

Ali H. Ellebedy ◽

Thomas P. Fabrizio ◽

Ghazi Kayali ◽

Thomas H. Oguin ◽

Scott A. Brown ◽

...

Keyword(s):

Influenza Virus ◽

Pandemic Influenza ◽

Influenza A ◽

Seasonal Influenza ◽

H1n1 Virus ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Inactivated Vaccine ◽

H1n1 Influenza Virus ◽

Influenza A H1n1

ABSTRACT Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.

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Zanamivir-Resistant Influenza Viruses with a Novel Neuraminidase Mutation

Journal of Virology ◽

10.1128/jvi.01200-09 ◽

2009 ◽

Vol 83 (20) ◽

pp. 10366-10373 ◽

Cited By ~ 158

Author(s):

Aeron C. Hurt ◽

Jessica K. Holien ◽

Michael Parker ◽

Anne Kelso ◽

Ian G. Barr

Keyword(s):

Southeast Asia ◽

Influenza A ◽

Seasonal Influenza ◽

Mdck Cells ◽

The United States ◽

Influenza Viruses ◽

Viral Fitness ◽

Wild Type Virus ◽

Clinical Specimens ◽

Influenza A H1n1

ABSTRACT The neuraminidase inhibitors zanamivir and oseltamivir are marketed for the treatment and prophylaxis of influenza and have been stockpiled by many countries for use in a pandemic. Although recent surveillance has identified a striking increase in the frequency of oseltamivir-resistant seasonal influenza A (H1N1) viruses in Europe, the United States, Oceania, and South Africa, to date there have been no reports of significant zanamivir resistance among influenza A (H1N1) viruses or any other human influenza viruses. We investigated the frequency of oseltamivir and zanamivir resistance in circulating seasonal influenza A (H1N1) viruses in Australasia and Southeast Asia. Analysis of 391 influenza A (H1N1) viruses isolated between 2006 and early 2008 from Australasia and Southeast Asia revealed nine viruses (2.3%) that demonstrated markedly reduced zanamivir susceptibility and contained a previously undescribed Gln136Lys (Q136K) neuraminidase mutation. The mutation had no effect on oseltamivir susceptibility but caused approximately a 300-fold and a 70-fold reduction in zanamivir and peramivir susceptibility, respectively. The role of the Q136K mutation in conferring zanamivir resistance was confirmed using reverse genetics. Interestingly, the mutation was not detected in the primary clinical specimens from which these mutant isolates were grown, suggesting that the resistant viruses either occurred in very low proportions in the primary clinical specimens or arose during MDCK cell culture passage. Compared to susceptible influenza A (H1N1) viruses, the Q136K mutant strains displayed greater viral fitness than the wild-type virus in MDCK cells but equivalent infectivity and transmissibility in a ferret model.

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Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors

Eurosurveillance ◽

10.2807/1560-7917.es2014.19.27.20849 ◽

2014 ◽

Vol 19 (27) ◽

Author(s):

U Perez-Sautu ◽

F Pozo ◽

I Cuesta ◽

S Monzon ◽

A Calderon ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Substitution ◽

Influenza A ◽

High Throughput Sequencing ◽

Biological Significance ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Neuraminidase Inhibitors ◽

Epidemic Season ◽

Influenza A H1n1

The Y155H amino acid substitution in the neuraminidase gene (NA) has previously been associated with highly reduced inhibition by neuraminidase inhibitors in the seasonal H1N1 influenza A virus which circulated in humans before the 2009 pandemic. During the 2012/13 epidemic season in Spain, two A(H1N1)pdm09 viruses bearing the specific Y155H substitution in the NA were detected and isolated from two patients diagnosed with severe respiratory syndrome and pneumonia requiring admission to the intensive care unit. Contrary to what was observed in the seasonal A(H1N1) viruses, neither of the Y155H A(H1N1)pdm09 viruses described here showed a phenotype of reduced inhibition by NAIs as determined by the neuraminidase enzyme inhibition assay (MUNANA). High-throughput sequencing of the NA of both Y155H viruses showed that they were composed to >99% of H155 variants. We believe that this report can contribute to a better understanding of the biological significance of amino acid substitutions in the neuraminidase protein with regard to susceptibility of influenza viruses to neuraminidase inhibitors. This is of critical importance for optimal management of influenza disease patients.

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The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase

mBio ◽

10.1128/mbio.00067-10 ◽

2010 ◽

Vol 1 (1) ◽

Cited By ~ 47

Author(s):

Brett W. Jagger ◽

Matthew J. Memoli ◽

Zong-Mei Sheng ◽

Li Qi ◽

Rachel J. Hrabal ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

H1n1 Virus ◽

Influenza Pandemic ◽

Influenza Infection ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Pandemic Virus ◽

2009 H1n1 ◽

Animal Reservoirs

ABSTRACTThe swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years. The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths. Given the virus’s recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential. We tested the hypothesis that mutations in the polymerase PB2 gene at residues 627 and 701 would enhance virulence but found that influenza viruses containing these mutations in the context of the pandemic virus polymerase complex are attenuated in cell culture and mice.IMPORTANCEInfluenza A virus (IAV) evolution is characterized by host-specific lineages, and IAVs derived in whole or in part from animal reservoirs have caused pandemics in humans. Because IAVs are known to acquire host-adaptive genome mutations, and since the PB2 gene of the 2009 H1N1 virus is of recent avian derivation, there exists concern that the pathogenicity of the 2009 H1N1 influenza A pandemic virus could be potentiated by acquisition of the host-adaptive PB2-E627K or -D701N mutations, which have been shown to enhance the virulence of other influenza viruses. We present data from a mouse model of influenza infection showing that such mutations do not increase the virulence of viruses containing the 2009 H1N1 viral polymerase.

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Infrarenal Aorta Thrombosis Associated with H1N1 Influenza A Virus Infection

Case Reports in Infectious Diseases ◽

10.1155/2016/9567495 ◽

2016 ◽

Vol 2016 ◽

pp. 1-3 ◽

Cited By ~ 2

Author(s):

Can Hüzmeli ◽

Mustafa Saglam ◽

Ali Arıkan ◽

Barıs Doner ◽

Gulay Akıncı ◽

...

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

H1n1 Virus ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Infrarenal Aorta ◽

Influenza A H1n1 ◽

Polymerase Chain ◽

Influenza A Virus Infection

Influenza viruses are members of the Orthomyxoviridae family, of which influenza A, B, and C viruses constitute three separate genera. Arterial thrombosis associated with H1N1 influenza A virus infection has rarely been reported. A Turkish man aged 28 years was admitted to our emergency department with dyspnea, bilateral lower extremity insensitivity, and cold. He reported symptoms of fever, myalgia, and cough, which he had had for fifteen days before being admitted to our hospital. The patient was tested for pandemic influenza A (H1N1) virus using polymerase chain reaction (PCR) tests, which were positive. Abdominal computerized tomography with contrast revealed a large occlusive thrombus within the infrarenal aorta.

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Impact of the Baloxavir-Resistant Polymerase Acid I38T Substitution on the Fitness of Contemporary Influenza A(H1N1)pdm09 and A(H3N2) Strains

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz418 ◽

2019 ◽

Vol 221 (1) ◽

pp. 63-70 ◽

Cited By ~ 17

Author(s):

Liva Checkmahomed ◽

Zeineb M’hamdi ◽

Julie Carbonneau ◽

Marie-Christine Venable ◽

Mariana Baz ◽

...

Keyword(s):

Influenza A ◽

Mdck Cells ◽

Influenza Viruses ◽

Recombinant Viruses ◽

Influenza A H1n1 ◽

2009 H1n1 ◽

Similar Weight ◽

Viral Subtypes ◽

The Impact

Abstract Background Baloxavir is a cap-dependent inhibitor of the polymerase acid (PA) protein of influenza viruses. While appearing virologically superior to oseltamivir, baloxavir exhibits a low barrier of resistance. We sought to assess the impact of the common baloxavir-resistant I38T PA substitution on in vitro properties and virulence. Methods Influenza A/Quebec/144147/2009 (H1N1)pdm09 and A/Switzerland/9715293/2013 (H3N2) recombinant viruses and their I38T PA mutants were compared in single and competitive infection experiments in ST6GalI-MDCK cells and C57/BL6 mice. Virus titers in cell culture supernatants and lung homogenates were determined by virus yield assays. Ratios of wild-type (WT) and I38T mutant were assessed by digital RT-PCR. Results I38T substitution did not alter the replication kinetics of A(H1N1)pdm09 and A(H3N2) viruses. In competition experiments, a 50%:50% mixture evolved to 70%:30% (WT/mutant) for A(H1N1) and 88%:12% for A(H3N2) viruses after a single cell passage. The I38T substitution remained stable after 4 passages in vitro. In mice, the WT and its I38T mutant induced similar weight loss with comparable lung titers in both viral subtypes. The mutant virus tended to predominate over the WT in mouse competition experiments. Conclusion The fitness of baloxavir-resistant I38T PA mutants appears relatively unaltered in seasonal subtypes warranting surveillance for its dissemination.

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2750. Sequential Influenza A H1N1 and Influenza A H3N2 Challenge Infections in Healthy Volunteers

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2427 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S969-S969 ◽

Cited By ~ 1

Author(s):

Alison Han ◽

Luca Giurgea ◽

Adriana Cervantes-Medina ◽

Kristina Edwards ◽

Luz Angela Rosas ◽

...

Keyword(s):

Healthy Volunteers ◽

Influenza A ◽

Reverse Genetics ◽

Clinical Symptoms ◽

Influenza Infection ◽

Influenza Viruses ◽

Wild Type ◽

Viral Shedding ◽

Influenza A H1n1 ◽

The Impact

Abstract Background Seasonal influenza causes significant annual morbidity and mortality. The effects of yearly exposures on immunity are not clear and recent observations have demonstrated that long lasting protection against a matched strain may not naturally occur. The 2018–2019 influenza season consisted of an initial peak of H1N1 infections followed by a wave of H3N2 infections. These consecutive waves raise questions about how influenza immunity is affected by sequential exposure to different influenza strains. Challenge studies provide a unique opportunity to study this phenomenon. Here we describe a subset of participants who were sequentially infected in two separate challenge studies with wild-type H1N1 and H3N2 viruses. Methods Healthy volunteers completed two sequential influenza challenge studies at the NIH Clinical Center. Participants were inoculated with reverse genetics, cell-based, GMP wild-type influenza viruses, A(H1N1)pdm09 and A(H3N2) strains. Participants remained isolated in the hospital for a minimum of 9 days and were monitored daily for viral shedding and clinical symptoms. After discharge, participants were followed for 2 months. Results Between 2014 and 2017, 14 healthy volunteers were exposed to Influenza A(H1N1) and Influenza A(H3N2). Time between infections ranged from 2 months to 2 years. Thirteen (93%) participants developed confirmed influenza infection after H1N1 challenge and 9 (64%) after H3N2 challenge. Eight (57%) participants developed confirmed infections after both exposures. Variable degrees of symptoms, shedding, and disease severity were observed. Systemic antibody responses to the HA and NA of both H1N1 and H3N2 varied over time during these sequential infections. Conclusion More than half of all participants who completed 2 sequential H1N1 and H3N2 challenge studies demonstrated confirmed infection to both viruses. These sequential infections had varying effects on the disease experienced and the immunity that developed after infection. These observations are important in understanding the impact of sequential exposures on influenza immunity. Disclosures All authors: No reported disclosures.

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SALIENT FEATURES OF CIRCULATING RESPIRATORY VIRUSES IN THE PRE– AND PANDEMIC INFLUENZA AND COVID–19 SEASONS

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-sfo-1662 ◽

2021 ◽

Author(s):

I. V. Kiseleva ◽

N. V. Larionova ◽

E. P. Grigorieva ◽

A. D. Ksenafontov ◽

M. Al Farroukh ◽

...

Keyword(s):

Pandemic Influenza ◽

Influenza A ◽

Influenza Infection ◽

Opportunity To Learn ◽

Respiratory Viruses ◽

Influenza Viruses ◽

Effective Prevention ◽

Pdm09 Virus ◽

Influenza A H1n1 ◽

Syncytial Virus

Abstract. A wide variety of zoonotic viruses that can cross the interspecies barrier promote the emergence of new, potentially pandemic viruses in the human population that was often accompanied by the disappearance of existing circulating strains. Among the various reasons underlying this phenomenon is the strengthening of populational immunity by expanding the immune layer of the population and improving the means and methods of medical care. However, “Natura abhorret vacuum”, and new pathogens come to replace disappearing pathogens. In the past ten years, there have been two critical events – the pandemic spread of the swine influenza A (H1N1) pdm09 virus in 2009 and the novel SARS–CoV–2 coronavirus in 2019, providing scientists with a unique opportunity to learn more about a relationship between respiratory viruses and their pathogenesis. Together with viruses of pandemic significance, a large number of seasonal respiratory viruses circulate, which contribute to the structure of human morbidity, and co–infections aggravate the condition of the illness. In the conditions of the spread of new viruses with unexplored characteristics, in the absence of means of prevention and therapy, it is especially important to prevent the aggravation of morbidity due to mixed infections. Here we review the mutual involvement of pandemic influenza A(H1N1)pdm09 and SARS–CoV–2 coronavirus and seasonal respiratory viruses in the epidemic process, discuss some issues related to their spread, potential causes affecting the spread and severity of the morbidity. The given facts, testify to the existence of seasonality and temporal patterns of the beginning and end of the circulation of respiratory viruses. Interestingly, the beginning of the circulation of the pandemic influenza A(H1N1)pdm09 virus led to a shift in the timing and intensity of circulation of some respiratory viruses, which is probably caused by the existence of "replication conflicts" between them, and did not affect others. Co–infection with SARS–CoV–2–19 and other respiratory viruses, especially respiratory syncytial virus and rhinoviruses, was quite often observed. At the current stage, no aggravating effect of influenza on the course of COVID–19 in mixed infection has been established. Whether this is due to the mild course of influenza infection in the 2020 epidemic season, or the competitive impact of SARS–CoV–2 on influenza viruses is not yet clear. Experts are still at the stage of accumulating facts and working on creating means of effective prevention and treatment of the new coronavirus infection.

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