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Brian R Wasik, Karen N Barnard, Robert J Ossiboff, Zahra Khedri, Kurtis H Feng, Hai Yu, Xi Chen, Daniel R Perez, Ajit Varki, Colin R Parrish
Sialic acids (Sias) are important glycans displayed on the cells and tissues of many different animals and are frequent targets for binding and modification by pathogens, including influenza viruses. Influenza virus hemagglutinins bind Sias during the infection of their normal hosts, while the encoded neuraminidases and/or esterases remove or modify the Sia to allow virion release or to prevent rebinding. Sias naturally occur in a variety of modified forms, and modified Sias can alter influenza virus host tropisms through their altered interactions with the viral glycoproteins...
September 2017: MSphere
Vivian K Leung, Natalie Spirason, Hilda Lau, Iwona Buettner, Sook-Kwan Leang, Michelle K Chow
As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System, the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a total of 5,557 influenza positive samples during 2015. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties. In 2015, influenza B viruses predominated over influenza A(H1)pdm09 and A(H3) viruses, accounting for a total of 58% of all viruses analysed. The vast majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2015...
June 30, 2017: Communicable Diseases Intelligence Quarterly Report
Taeeun Kim, Choong Eun Jin, Heungsup Sung, Bonhan Koo, Joungha Park, Sun-Mi Kim, Ji Yeun Kim, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Jung-Hee Lee, Je-Hwan Lee, Kyoo-Hyung Lee, Yong Shin, Sung-Han Kim
BACKGROUND: Although fomites or contaminated surfaces have been considered as transmission routes, the role of environmental contamination by human parainfluenza virus type 3 (hPIV-3) in healthcare settings is not established. AIM: To describe an hPIV-3 nosocomial outbreak and the results of environmental sampling to elucidate the source of nosocomial transmission and the role of environmental contamination. METHODS: During an hPIV-3 outbreak between May and June 2016, we swabbed environmental surfaces in contact with clustered patients and used respiratory specimens from infected patients and epidemiologically unlinked controls...
September 8, 2017: Journal of Hospital Infection
Megan L Shaw
Options for influenza therapy are currently limited to one class of drug, the neuraminidase inhibitors. Amidst concerns about drug resistance, much effort has been placed on the discovery of new drugs with distinct targets and mechanisms of action, with great success. There are now several candidates in late stage development which include small molecules targeting the three subunits of the viral polymerase complex and monoclonal antibodies targeting the hemagglutinin, as well as host-directed therapies. The availability of drugs with diverse mechanisms now opens the door to exploring combination therapies for influenza, and the range of administration routes presents more opportunities for treating hospitalized patients...
September 11, 2017: ACS Infectious Diseases
Jason R Wilson, Jessica A Belser, Juliana DaSilva, Zhu Guo, Xiangjie Sun, Shane Gansebom, Yaohui Bai, Thomas J Stark, Jessie Chang, Paul Carney, Min Z Levine, John Barnes, James Stevens, Taronna R Maines, Terrence M Tumpey, Ian A York
The emergence of A(H7N9) virus strains with resistance to neuraminidase (NA) inhibitors highlights a critical need to discover new countermeasures for treatment of A(H7N9) virus-infected patients. We previously described an anti-NA mAb (3c10-3) that has prophylactic and therapeutic efficacy in mice lethally challenged with A(H7N9) virus when delivered intraperitoneally (i.p.). Here we show that intrananasal (i.n.) administration of 3c10-3 protects 100% of mice from mortality when treated 24h post-challenge and further characterize the protective efficacy of 3c10-3 using a nonlethal A(H7N9) challenge model...
September 6, 2017: Virology
Yu-Jin Kim, Eun-Ju Ko, Min-Chul Kim, Yu-Na Lee, Ki-Hye Kim, Yu-Jin Jung, Sang-Moo Kang
Although neuraminidase (NA) is the second major viral glycoprotein of influenza virus, its immune mechanism as a vaccine target has been less considered. Here we compared the properties of antibodies and the efficacy of cross protection by N1 and N2 NA proteins, inactivated split influenza vaccines (split), and tandem repeat extracellular domain M2 on virus-like particles (M2e5x VLP). Anti-NA immune sera could confer better cross-protection against multiple heterologous influenza viruses correlating with NA inhibition activity compared to split vaccine immune sera...
September 5, 2017: Biochemical and Biophysical Research Communications
Martin Bitzan, Jakub Zieg
Thrombotic microangiopathy (TMA) refers to phenotypically similar disorders, including hemolytic uremic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP). This review explores the role of the influenza virus as trigger of HUS or TTP. We conducted a literature survey in PubMed and Google Scholar using HUS, TTP, TMA, and influenza as keywords, and extracted and analyzed reported epidemiological and clinical data. We identified 25 cases of influenza-associated TMA. Five additional cases were linked to influenza vaccination and analyzed separately...
September 7, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Sehee Park, Jin Il Kim, Ilseob Lee, Joon-Yong Bae, Kirim Yoo, Misun Nam, Juwon Kim, Mee Sook Park, Ki-Joon Song, Jin-Won Song, Sun-Ho Kee, Man-Seong Park
It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry. We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice. The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region. To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics...
September 7, 2017: Scientific Reports
Ji-Hui Jin, Jin-Long Cheng, Zi-Rong He, Ying-Chao Ren, Xiao-Hui Yu, Yang Song, Hui-Ming Yang, Yan-Ling Yang, Tong Liu, Guo-Zhong Zhang
To investigate the exact effects of different origins of Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) protein to the biological characteristics of the virus, we systematically studied the correlation between the HN protein and NDV virulence by exchanging the HN of velogenic or lentogenic NDV strains with the HN from other strains of different virulence. The results revealed that the rSG10 or rLaSota derivatives bearing the HN gene of other viruses exhibited decreased or increased hemadsorption (HAd), neuraminidase and fusion promotion activities...
2017: Frontiers in Microbiology
Gwladys C Monamele, Marie-Astrid Vernet, Mohammed R Njankouo, Kathleen Victoir, Jane Francis Akoachere, Damian Anong, Richard Njouom
The first outbreak of influenza A(H3N2) occurred in 1968 and caused the third flu pandemic of the 20th century. It has affected multiple countries over time. The best strategy to reduce the burden of influenza is through vaccination whose efficacy varies with respect to the circulating strains. This study was performed to better understand the molecular evolution of influenza A(H3N2) and assess vaccine efficacy in Cameroon. Complete sequences of three gene segments were obtained from 2014 to 2016 influenza seasons in Cameroon...
2017: PloS One
Masayoshi Higashiguchi, Tomoshige Matsumoto, Takashi Fujii
BACKGROUND: Laninamivir octanoate is a recently developed inhaled neuraminidase inhibitor for treating influenza virus infection. We performed meta-analyses to clarify the efficacy of laninamivir octanoate on influenza treatment and prevention. METHODS: MEDLINE and CENTRAL were searched to identify eligible studies. The log median time to event ratios (logMRs) and log odds ratios (logORs) were combined with meta-analysis. RESULTS: Nine studies in treatment settings and three studies in prophylaxis settings were eligible for this meta-analysis...
September 4, 2017: Antiviral Therapy
Mahmoud M Naguib, Abdel-Satar Arafa, Rokshana Parvin, Martin Beer, Thomas Vahlenkamp, Timm C Harder
Low pathogenic avian influenza (LPAI) H9N2 viruses have established endemic status in Egyptian poultry populations since 2012. Recently, four cases of human H9N2 virus infections in Egypt demonstrated the zoonotic potential of these viruses. Egyptian H9N2 viruses obtained from 2011 to 2014 phylogenetically grouped into three clusters (1-3) within subclade B of the G1 lineage. Antigenically, a close clustering of the Egyptian H9N2 viruses with other recent G1-B like H9N2 strains and a significant antigenic distance from viruses outside the G1-B lineage was evident...
August 29, 2017: Virology
Yi-Min She, Aaron Farnsworth, Xuguang Li, Terry D Cyr
The outbreak of a pandemic influenza H1N1 in 2009 required the rapid generation of high-yielding vaccines against the A/California/7/2009 virus, which were achieved by either addition or deletion of a glycosylation site in the influenza proteins hemagglutinin and neuraminidase. In this report, we have systematically evaluated the glycan composition, structural distribution and topology of glycosylation for two high-yield candidate reassortant vaccines (NIBRG-121xp and NYMC-X181A) by combining various enzymatic digestions with high performance liquid chromatography and multiple-stage mass spectrometry...
August 31, 2017: Scientific Reports
Liqi Liu, Jian Lu, Jianfang Zhou, Zi Li, Heng Zhang, Dayan Wang, Yuelong Shu
Human infections with Eurasian avian-like swine influenza H1N1 viruses have been reported in China in past years. One case resulted in death and others were mild case. In 2016, the World Health Organization recommended the use of A/Hunan/42443/2015(H1N1) virus to construct the first candidate vaccine strain for Eurasian avian-like swine influenza H1N1 viruses. Previous reports showed that the neuraminidase of A/Puerto Rico/8/34(H1N1) might improve the viral yield of reassortant viruses. Therefore, we constructed two reassortant candidate vaccine viruses of A/Hunan/42443/2015(H1N1) by reverse genetic technology, with (6+2) and (7+1) gene constitution, respectively...
August 28, 2017: Microbes and Infection
Chung-Young Lee, Hyuk-Joon Kwon, Thanh Trung Nguyen, Ilhwan Kim, Hyung-Kwan Jang, Jae-Hong Kim
Twelve nucleotides located at the 3' end of viral genomic RNA (vRNA) are conserved among influenza A viruses (IAV) and have a promoter function. Hoffmann's 8-plasmid reverse genetics vector system introduced mutations at position 4, C nucleotide (C4) to U nucleotide (U4), of the 3' ends of neuraminidase (NA) and matrix (M) vRNAs of wild-type A/PR/8/34 (PR8). This resulted in a constellation of C4 and U4 vRNAs coding for low (polymerases) and relatively high (all others) copy number proteins, respectively. U4 has been reported to increase promoter activity in comparison to C4, but the constellation effect on the replication efficiency and pathogenicity of reverse genetics PR8 (rgPR8) has not been fully elucidated...
August 31, 2017: Journal of Veterinary Science
Jin-Wook Jang, Chung-Young Lee, Il-Hwan Kim, Jun-Gu Choi, Youn-Jeong Lee, Seong-Su Yuk, Ji-Ho Lee, Chang-Seon Song, Jae-Hong Kim, Hyuk-Joon Kwon
A/Puerto Rico/8/34 (PR8)-derived recombinant viruses have been used for seasonal flu vaccines; however, they are insufficient for vaccines against some human-fatal H5N1 highly pathogenic avian influenza (HPAI) viruses (HPAIV) due to low productivity. Additionally, the polymerase basic 2 (PB2) protein, an important mammalian-pathogenicity determinant, of PR8 possesses several mammalian-pathogenic mutations. We previously reported two avian PB2 genes (01310 and 0028) related to efficient replication in embryonated chicken eggs (ECEs) and nonpathogenicity in BALB/c mice...
August 31, 2017: Journal of Veterinary Science
Gabriela Arévalo-Pinzón, Maritza Bermúdez, Diana Hernández, Hernando Curtidor, Manuel Alfonso Patarroyo
The malarial parasite's invasion is complex, active and coordinated, involving many low and high affinity interactions with receptors on target cell membrane. Proteomics analysis has described around 40 proteins in P. vivax which could be involved in reticulocyte invasion; few have been studied with the aim of elucidating how many of them establish specific interactions with their respective host cells. Given the importance of knowing which of the parasite's protein regions are functionally important for invasion, minimum regions mediating specific interaction between Plasmodium vivax apical membrane antigen 1 (PvAMA-1) and its host cell were here elucidated...
August 30, 2017: Scientific Reports
Nguyen Minh Tam, Minh Tho Nguyen, Son Tung Ngo
The absolute free energy difference of binding (ΔG) between neuraminidase and its inhibitor was evaluated using fast pulling of ligand (FPL) method over steered molecular dynamics (SMD) simulations. The metric was computed through linear interaction approximation. Binding nature was described by free energy differences of electrostatic and van der Waals (vdW) interactions. The finding indicates that vdW metric is dominant over electrostatics in binding process. The computed values are in good agreement with experimental data with a correlation coefficient of R=0...
August 24, 2017: Journal of Molecular Graphics & Modelling
Yacine Abed, Guy Boivin
Anti-influenza drugs play major roles in the management of severe influenza infections. Neuraminidase inhibitors (NAIs), which are active against all influenza A subtypes and the 2 major influenza B lineages, constitute the only class of antivirals recommended for the control of influenza epidemics and eventual pandemics. Thus, the emergence of NAI resistance could be a major clinical concern. Although most currently circulating influenza A and B strains are susceptible to NAIs, clinical cases of influenza viruses harboring single or multiple NA substitutions or deletions conferring a cross-resistance phenotype to the 2 main NAIs (oseltamivir and zanamivir) have been reported, mostly in immunocompromised individuals...
2017: Open Forum Infectious Diseases
R Roosenhoff, A van der Linden, M Schutten, R A M Fouchier
No abstract text is available yet for this article.
March 2017: Virus Evolution
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