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Influenza H1n1

Simone La Frazia, Sara Piacentini, Anna Riccio, Jean Francois Rossignol, M Gabriella Santoro
The emergence of new avian influenza virus (AIV) strains able to infect humans represents a serious threat to global human health. In addition to surveillance and vaccine development, antiviral therapy remains crucial for AIV control; however, the increase in drug-resistant AIV strains underscores the need for novel approaches to anti-influenza chemotherapy. We have previously shown that the thiazolide anti-infective nitazoxanide (NTZ) inhibits influenza A/PuertoRico/8/1934(H1N1) virus replication, and this effect was associated with inhibition of viral hemagglutinin (HA) maturation...
June 13, 2018: Antiviral Research
Hanjun Zhao, Kelvin K W To, Hin Chu, Qiulu Ding, Xiaoyu Zhao, Cun Li, Huiping Shuai, Shuofeng Yuan, Jie Zhou, Kin-Hang Kok, Shibo Jiang, Kwok-Yung Yuen
Limited efficacy of current antivirals and antiviral-resistant mutations impairs anti-influenza treatment. Here, we evaluate the in vitro and in vivo antiviral effect of three defective interfering genes (DIG-3) of influenza virus. Viral replication is significantly reduced in cell lines transfected with DIG-3. Mice treated with DIG-3 encoded by jetPEI-vector, as prophylaxis and therapeutics against A(H7N7) virus, respectively, have significantly better survivals (80% and 50%) than control mice (0%). We further develop a dual-functional peptide TAT-P1, which delivers DIG-3 with high efficiency and concomitantly exerts antiviral activity by preventing endosomal acidification...
June 15, 2018: Nature Communications
Bei Wang, Tze Hau Lam, Mun Kuen Soh, Zhiyong Ye, Jinmiao Chen, Ee Chee Ren
Human influenza virus (IAV) are among the most common pathogens to cause human respiratory infections. A better understanding on interplay between IAV and host factors may provide clues for disease prevention and control. While many viruses are known to downregulate p53 upon entering the cell to reduce the innate host antiviral response, IAV infection is unusual in that it activates p53. However, it has not been clear whether this process has proviral or antiviral effects. In this study, using human isogenic p53 wild-type and p53null A549 cells generated from the CRISPR/Cas9 technology, we observed that p53null cells exhibit significantly reduced viral propagation when infected with influenza A virus (strain A/Puerto Rico/8/1934 H1N1)...
2018: Frontiers in Immunology
Hui Cai, Meisui Liu, Charles J Russell
Reporter viruses provide a powerful tool to study infection, yet incorporating a non-essential gene often results in virus attenuation and genetic instability. Here, we used directed evolution of a luciferase-expressing pandemic H1N1 (pH1N1) 2009 influenza A virus in mice to restore replication kinetics and virulence, increase the bioluminescence signal, and maintain reporter gene expression. An unadapted pH1N1 virus with NanoLuc luciferase inserted into the 5' end of the PA gene segment grew to titers 10-fold less than wild-type in MDCK cells and in DBA/2 mice and was less virulent...
June 13, 2018: Journal of Virology
Raffael Nachbagauer, David Shore, Hua Yang, Scott K Johnson, Jon D Gabbard, S Mark Tompkins, Jens Wrammert, Patrick C Wilson, James Stevens, Rafi Ahmed, Florian Krammer, Ali H Ellebedy
Broadly cross-reactive antibodies that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (mAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus...
June 13, 2018: Journal of Virology
Daniel A Green, Kirsten St George
Rapid antigen tests for influenza, herein referred to as rapid influenza diagnostic tests (RIDTs), have been widely used for the diagnosis of influenza since their introduction in the 1990's due to their ease of use, rapid results, and suitability for point of care (POC) testing. However, issues related to the diagnostic sensitivity of these assays have been known for decades, and these issues gained greater attention following reports of their poor performance during the 2009 influenza A (H1N1) pandemic. In turn, significant concerns arose about the consequences of false negative results, which could pose significant risks to both individual patient care and to public health efforts...
June 13, 2018: Journal of Clinical Microbiology
K Russell, K Herrick, H Venkat, S Brady, K Komatsu, K Goodin, V Berisha, R Sunenshine, C Perez-Velez, S Elliott, S J Olsen, C Reed
The Arizona Department of Health Services identified unusually high levels of influenza activity and severe complications during the 2015-2016 influenza season leading to concerns about potential increased disease severity compared with prior seasons. We estimated state-level burden and severity to compare across three seasons using multiple data sources for community-level illness, hospitalisation and death. Severity ratios were calculated as the number of hospitalisations or deaths per community case. Community influenza-like illness rates, hospitalisation rates and mortality rates in 2015-2016 were higher than the previous two seasons...
June 14, 2018: Epidemiology and Infection
K Malbari, H Gonsalves, A Chintakrindi, D Gohil, M Joshi, S Kothari, S Srivastava, A Chowdhary, M Kanyalkar
Considering the need for discovery of new antiviral drugs, in view to combat the issue of resistance particularly to anti-influenza drugs, a series of 2'-amino, 3'-amino and 2', 4'-dihydroxy chalcone derivatives were designed. Structure-based drug design was used to design inhibitors of influenza virus - H1N1 neuraminidase enzyme. These were further optimized by a combination of iterative medicinal chemistry principles and molecular docking. Based on the best docking scores, some chalcone derivatives were synthesized and characterized by infrared spectroscopy (IR) and proton nuclear magnetic resonance (NMR)...
2018: Acta Virologica
Mai-Chi Trieu, Åsne Jul-Larsen, Marianne Sævik, Anders Madsen, Jane Kristin Nøstbakken, Fan Zhou, Steinar Skrede, Rebecca Jane Cox
Background: The 2009 influenza pandemic was caused by A/H1N1pdm09 virus, which was subsequently included in the seasonal vaccine as the A/H1N1 strain up to 2016/17. This provided a unique opportunity to investigate the antibody response to H1N1pdm09 over time. Methods: Healthcare workers (HCWs) were immunized with the AS03-adjuvanted H1N1pdm09 vaccine in 2009 (N=250), and subsequently vaccinated with seasonal vaccines containing H1N1pdm09 for 4 seasons (repeated group), <4 seasons (occasional group), or received no further vaccinations (single group)...
June 9, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Jie Zhou, Cun Li, Norman Sachs, Man Chun Chiu, Bosco Ho-Yin Wong, Hin Chu, Vincent Kwok-Man Poon, Dong Wang, Xiaoyu Zhao, Lei Wen, Wenjun Song, Shuofeng Yuan, Kenneth Kak-Yuen Wong, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Honglin Chen, Hans Clevers, Kwok-Yung Yuen
Novel reassortant avian influenza H7N9 virus and pandemic 2009 H1N1 (H1N1pdm) virus cause human infections, while avian H7N2 and swine H1N1 virus mainly infect birds and pigs, respectively. There is no robust in vitro model for assessing the infectivity of emerging viruses in humans. Based on a recently established method, we generated long-term expanding 3D human airway organoids which accommodate four types of airway epithelial cells: ciliated, goblet, club, and basal cells. We report differentiation conditions which increase ciliated cell numbers to a nearly physiological level with synchronously beating cilia readily discernible in every organoid...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Bernadett Boda, Sacha Benaoudia, Song Huang, Rosy Bonfante, Ludovic Wiszniewski, Eirini D Tseligka, Caroline Tapparel, Samuel Constant
Respiratory viral infections cause mild to severe diseases, such as common cold, bronchiolitis and pneumonia and are associated with substantial burden for society. To test new molecules for shortening, alleviating the diseases or to develop new therapies, relevant human in vitro models are mandatory. MucilAir™, a human standardized air-liquid interface 3D airway epithelial culture holds in vitro specific mechanisms to counter invaders comparable to the in vivo situation, such as mucus production, mucociliary clearance, and secretion of defensive molecules...
June 8, 2018: Antiviral Research
Binghui Xia, Jiansheng Lu, Rong Wang, Zhixin Yang, Xiaowei Zhou, Peitang Huang
Influenza A virus (IAV) is responsible for severe morbidity and mortality in animals and humans worldwide. miRNAs are a class of small noncoding single-stranded RNA molecules that can negatively regulate gene expression and play important roles in virus-host interaction. However, the roles of miRNAs in IAV infection are still not fully understood. Here, we profiled the cellular miRNAs of A549 cells infected with A/goose/Jilin/hb/2003 (H5N1) and a comparison A/Beijing/501/2009 (H1N1). miRNA microarray and quantitative PCR analysis showed that several miRNAs were differentially expressed in A549 cells during IAV infection...
2018: Frontiers in Cellular and Infection Microbiology
F Wang, Y Qian, J Deng, Y Sun, L Q Zhao, R Tian, R N Zhu
Objective: To analyze and compare the epidemiological features of prevalent influenza A viruses in children in Beijing during 13 consecutive surveillance seasons from 2004 to 2017. Methods: This was a repeated cross section study. Throat swabs were collected weekly from children with influenza-like illnesses (ILI) who presented to the outpatient/emergency department of Children's Hospital, Capital Institute of Pediatrics during the period from September, 2004 to August, 2017. All of the specimens were inoculated into Madin Darby canine kidney (MDCK) cells to isolate influenza viruses followed by identifying different types of influenza viruses with reference antisera by hemagglutination-inhibition assay...
June 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Saverio Caini, Peter Spreeuwenberg, Gabriela F Kusznierz, Juan Manuel Rudi, Rhonda Owen, Kate Pennington, Sonam Wangchuk, Sonam Gyeltshen, Walquiria Aparecida Ferreira de Almeida, Cláudio Maierovitch Pessanha Henriques, Richard Njouom, Marie-Astrid Vernet, Rodrigo A Fasce, Winston Andrade, Hongjie Yu, Luzhao Feng, Juan Yang, Zhibin Peng, Jenny Lara, Alfredo Bruno, Doménica de Mora, Celina de Lozano, Maria Zambon, Richard Pebody, Leticia Castillo, Alexey W Clara, Maria Luisa Matute, Herman Kosasih, Nurhayati, Simona Puzelli, Caterina Rizzo, Herve A Kadjo, Coulibaly Daouda, Lyazzat Kiyanbekova, Akerke Ospanova, Joshua A Mott, Gideon O Emukule, Jean-Michel Heraud, Norosoa Harline Razanajatovo, Amal Barakat, Fatima El Falaki, Sue Q Huang, Liza Lopez, Angel Balmaseda, Brechla Moreno, Ana Paula Rodrigues, Raquel Guiomar, Li Wei Ang, Vernon Jian Ming Lee, Marietjie Venter, Cheryl Cohen, Selim Badur, Meral A Ciblak, Alla Mironenko, Olha Holubka, Joseph Bresee, Lynnette Brammer, Phuong Vu Mai Hoang, Mai Thi Quynh Le, Douglas Fleming, Clotilde El-Guerche Séblain, François Schellevis, John Paget
BACKGROUND: Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases). METHODS: For each virus, we calculated a Relative Illness Ratio (defined as the ratio of the percentage of cases in an age group to the percentage of the country population in the same age group) for young children (0-4 years), older children (5-17 years), young adults (18-39 years), older adults (40-64 years), and the elderly (65+ years)...
June 8, 2018: BMC Infectious Diseases
Mélia Magnen, Brigitta Margit Elsässer, Olga Zbodakova, Petr Kasparek, Fabien Gueugnon, Agnès Petit-Courty, Radislav Sedlacek, Peter Goettig, Yves Courty
Every year, influenza A virus (IAV) affects and kills many humans worldwide. The viral hemagglutinin (HA) is a critical actor of influenza virus infectivity which needs to be cleaved by host serine proteases to exert its activity. KLK5 has been identified as an activating protease in humans with a preference for the H3N2 IAV subtype. We investigated the origin of this preference using influenza A/Puerto Rico/8/34 (PR8, H1N1) and A/Scotland/20/74 (Scotland, H3N2) viruses. Pretreatment of noninfectious virions with human KLK5 increased infectivity of Scotland IAV in MDCK cells and triggered influenza pneumonia in mice...
December 20, 2017: Biological Chemistry
Ithaisa Sologuren, María Teresa Martínez-Saavedra, Jordi Solé-Violán, Edgar de Borges de Oliveira, Eva Betancor, Inmaculada Casas, Carmen Oleaga-Quintas, Mónica Martínez-Gallo, Shen-Ying Zhang, Jose Pestano, Roger Colobran, Estefanía Herrera-Ramos, Carmen Pérez, Marta López-Rodríguez, José Juan Ruiz-Hernández, Nieves Franco, José María Ferrer, Cristina Bilbao, Miguel Andújar-Sánchez, Mercedes Álvarez Fernández, Michael J Ciancanelli, Felipe Rodríguez de Castro, Jean-Laurent Casanova, Jacinta Bustamante, Carlos Rodríguez-Gallego
The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2)...
June 7, 2018: Journal of Clinical Immunology
Xueting Fan, Qiudong Su, Feng Qiu, Yao Yi, Liping Shen, Zhiyuan Jia, Pu Liang, Yening Zou, Shengli Bi
Vaccine adjuvants are essential for enhancing immune responses during vaccination. However, only a limited number of safe and effective adjuvants, especially mucosal adjuvants, are available for use in vaccines. The development of a practically applicable mucosal adjuvant is therefore urgently needed. Here, we showed that the non-toxic CTA1-DD adjuvant, which combined the full enzymatic activity of the A1 subunit of cholera toxin (CT) with two immunoglobulin-binding domains of Staphylococcus aureus protein A (SpA), promoted mucosal and systemic humoral and cell-mediated immune responses following intranasal administration with H1N1 split vaccine in mice...
June 4, 2018: Vaccine
Gabriela Fontanella Biondo, João Carlos Santana, Patrícia M Lago, Jefferson Piva, Paulo Ricardo A Souza, Joana Genz Gaulke, Juliana M Sebben
BACKGROUND: A/H1N1 influenza is a viral disease that affects a significant part of the population mainly in winter, leading to increased number of medical consultations, hospitalizations and consequently care spending in emergency. METHODS: This is a case-series retrospective study, involving patients admitted to a tertiary hospital in southern Brazil in 2016 with a clinical diagnosis of acute respiratory infection of the influenza type and laboratory confirmation of influenza A/H1N1...
June 4, 2018: Brazilian Journal of Infectious Diseases
Chisato Imai, Michiko Toizumi, Lisa Hall, Stephen Lambert, Kate Halton, Katharina Merollini
BACKGROUND: Influenza vaccination is a commonly used intervention to prevent influenza infection in healthcare workers (HCWs) and onward transmission to other staff and patients. We undertook a systematic review to synthesize the latest evidence of the direct epidemiological and economic effectiveness of seasonal influenza vaccination among HCW. METHODS: We conducted a systematic search of MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials from 1980 through January 2018...
2018: PloS One
Rebecca Garten, Lenee Blanton, Anwar Isa Abd Elal, Noreen Alabi, John Barnes, Matthew Biggerstaff, Lynnette Brammer, Alicia P Budd, Erin Burns, Charisse N Cummings, Todd Davis, Shikha Garg, Larisa Gubareva, Yunho Jang, Krista Kniss, Natalie Kramer, Stephen Lindstrom, Desiree Mustaquim, Alissa O'Halloran, Wendy Sessions, Calli Taylor, Xiyan Xu, Vivien G Dugan, Alicia M Fry, David E Wentworth, Jacqueline Katz, Daniel Jernigan
The United States 2017-18 influenza season (October 1, 2017-May 19, 2018) was a high severity season with high levels of outpatient clinic and emergency department visits for influenza-like illness (ILI), high influenza-related hospitalization rates, and elevated and geographically widespread influenza activity across the country for an extended period. Nationally, ILI activity began increasing in November, reaching an extended period of high activity during January-February, and remaining elevated through March...
June 8, 2018: MMWR. Morbidity and Mortality Weekly Report
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