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Influenza hemagglutinin

Max Schelker, Caroline Maria Mair, Fabian Jolmes, Robert-William Welke, Edda Klipp, Andreas Herrmann, Max Flöttmann, Christian Sieben
After endocytic uptake, influenza viruses transit early endosomal compartments and eventually reach late endosomes. There, the viral glycoprotein hemagglutinin (HA) triggers fusion between endosomal and viral membrane, a critical step that leads to release of the viral segmented genome destined to reach the cell nucleus. Endosomal maturation is a complex process involving acidification of the endosomal lumen as well as endosome motility along microtubules. While the pH drop is clearly critical for the conformational change and membrane fusion activity of HA, the effect of intracellular transport dynamics on the progress of infection remains largely unclear...
October 2016: PLoS Computational Biology
Tyler Shelby, Tuhina Banerjee, Jyothi Kallu, Shoukath Sulthana, Irene Zegar, Santimukul Santra
Rapid detection and diagnosis of pathogenic strains of influenza is necessary for expedited treatment and quicker resolutions to the ever-rising flu pandemics. Considering this, we propose the development of novel magnetic relaxation nanosensors (MRnS) for the rapid detection of influenza through targeted binding with hemagglutinin. 2,6- and 2,3-sialic acid ligands and entry blocker peptides are conjugated to iron oxide nanoparticles to create functional MRnS. Positive detection of various hemagglutinin variants (H1 and H5) is possible with protein concentrations as little as 1...
October 25, 2016: Nanoscale
T Ilyicheva, A Durymanov, I Susloparov, N Kolosova, N Goncharova, S Svyatchenko, O Petrova, A Bondar, V Mikheev, A Ryzhikov
The influenza epidemic in 2015-2016 in Russia is characterized by a sharp increase of influenza cases (beginning from the second week of 2016) with increased fatalities. Influenza was confirmed in 20 fatal cases registered among children (0-10 years), in 5 cases among pregnant women, and in 173 cases among elderly people (60 years and older). Two hundred and ninety nine people died from influenza were patients with some chronic problems. The overwhelming majority among the deceased (more than 98%) were not vaccinated against influenza...
2016: PloS One
Seok-Joon Kwon, Dong Hee Na, Jong Hwan Kwak, Marc Douaisi, Fuming Zhang, Eun Ji Park, Jong-Hwan Park, Hana Youn, Chang-Seon Song, Ravi S Kane, Jonathan S Dordick, Kyung Bok Lee, Robert J Linhardt
Rapid change and zoonotic transmission to humans have enhanced the virulence of the influenza A virus (IAV). Neutralizing antibodies fail to provide lasting protection from seasonal epidemics. Furthermore, the effectiveness of anti-influenza neuraminidase inhibitors has declined because of drug resistance. Drugs that can block viral attachment and cell entry independent of antigenic evolution or drug resistance might address these problems. We show that multivalent 6'-sialyllactose-polyamidoamine (6SL-PAMAM) conjugates, when designed to have well-defined ligand valencies and spacings, can effectively inhibit IAV infection...
October 24, 2016: Nature Nanotechnology
Christina Kratsch, Thorsten R Klingen, Linda Mümken, Lars Steinbrück, Alice C McHardy
Human influenza viruses are rapidly evolving RNA viruses that cause short-term respiratory infections with substantial morbidity and mortality in annual epidemics. Uncovering the general principles of viral coevolution with human hosts is important for pathogen surveillance and vaccine design. Protein regions are an appropriate model for the interactions between two macromolecules, but the currently used epitope definition for the major antigen of influenza viruses, namely hemagglutinin, is very broad. Here, we combined genetic, evolutionary, antigenic, and structural information to determine the most relevant regions of the hemagglutinin of human influenza A/H3N2 viruses for interaction with human immunoglobulins...
January 2016: Virus Evolution
Karen K Yam, Angela Brewer, Virginie Bleau, Édith Beaulieu, Corey P Mallett, Brian J Ward
We investigated the long-term immune profiles of dose-sparing, AS03-adjuvanted vaccines compared to a traditional high-dose, unadjuvated influenza vaccine formulations. BALB/c mice received 2 IM injections of influenza A/Uruguay/716/2007 (H3N2) split vaccine antigen: high-dose (HD) (3 µg hemagglutinin (HA)/dose) or low-dose (LD) formulations (0.03 µg or 0.003 µg HA) with AS03 and were followed to 34 weeks post-boost (pb). We examined serologic responses, spleen and bone marrow (BM) HA-specific antibody-secreting cells (ASCs) by ELISpot, influenza-specific cytokine/chemokine production in re-stimulated splenocytes by multiplex ELISA, and antigen-specific CD4+ T cells that express cytokines (IL-2, IFNγ, TNFa and IL-5) by flow cytometry...
October 21, 2016: Human Vaccines & Immunotherapeutics
Wenfei Zhu, Hong Zhang, Xingyu Xiang, Lili Zhong, Lei Yang, Junfeng Guo, Yiran Xie, Fangcai Li, Zhihong Deng, Hong Feng, Yiwei Huang, Shixiong Hu, Xin Xu, Xiaohui Zou, Xiaodan Li, Tian Bai, Yongkun Chen, Zi Li, Junhua Li, Yuelong Shu
In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus...
November 2016: Emerging Infectious Diseases
Mamoona Chaudhry, Maqbool Ahmad, Hamad Bin Rashid, Bakhat Sultan, Haroon Rashid Chaudhry, Aayesha Riaz, Muhammad Shabir Shaheen
A prospective study was conducted from November 2013 to February 2014 to estimate the spatial clustering; cumulative incidence and risk factors associated with avian influenza (AI) subtype H9 infection on commercial poultry farms of Pakistan. A total of 400 farms were enrolled and followed during the study period. Among these, 109 farms submitted samples suspected for AI to the laboratory, and only 47 farms were confirmed positive by hemagglutinin inhibition (HI) test. Data was collected from these 109 farms about their demography, management, and biosecurity practices...
October 20, 2016: Tropical Animal Health and Production
Aleksandar Antanasijevic, Nicholas J Hafeman, Smanla Tundup, Carolyn Kingsley, Rama K Mishra, Lijun Rong, Balaji Manicassamy, Duncan Wardrop, Michael Caffrey
The viral envelope protein hemagglutinin (HA) plays a critical role in influenza entry and thus is an attractive target for novel therapeutics. The small molecule tert-butylhydroquinone (TBHQ) has previously been shown to bind to HA and inhibit HA-mediated entry with low micromolar potency. However, enthusiasm for the use of TBHQ has diminished due to the compound's antioxidant properties. In this work we show that the antioxidant properties of TBHQ are not responsible for the inhibition of HA-mediated entry...
September 9, 2016: ACS Infectious Diseases
Makoto Kawaguchi, Noboru Hara, Vladimir Bilim, Hiroshi Koike, Mituko Suzuki, Tae-Sun Kim, Nan Gao, Yu Dong, Sheng Zhang, Yuji Fujinawa, Osamu Yamamoto, Hiromi Ito, Yoshihiko Tomita, Yuchi Naruse, Akira Sakamaki, Yoko Ishii, Koichi Tsuneyama, Masaaki Inoue, Johbu Itoh, Masanori Yasuda, Nobuo Sakata, Cha-Gyun Jung, Satoshi Kanazawa, Hiroyasu Akatsu, Hiroshi Minato, Takayuki Nojima, Kiyofumi Asai, Yutaka Miura
BACKGROUND: Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma...
October 18, 2016: BMC Cancer
Boopathy Ramakrishnan, Karthik Viswanathan, Kannan Tharakaraman, Vlado Dančík, Rahul Raman, Gregory J Babcock, Zachary Shriver, Ram Sasisekharan
Broadly neutralizing monoclonal antibodies (bNAbs) for viral infections, such as HIV, respiratory syncytial virus (RSV), and influenza, are increasingly entering clinical development. For influenza, most neutralizing antibodies target influenza virus hemagglutinin. These bNAbs represent an emerging, promising modality for treatment and prophylaxis of influenza due to their multiple mechanisms of antiviral action and generally safe profile. Preclinical work in other viral diseases, such as dengue, has demonstrated the potential for antibody-based therapies to enhance viral uptake, leading to enhanced viremia and worsening of disease...
October 14, 2016: Trends in Microbiology
Freek Cox, Ted Kwaks, Boerries Brandenburg, Martin H Koldijk, Vincent Klaren, Bastiaan Smal, Hans J W M Korse, Eric Geelen, Lisanne Tettero, David Zuijdgeest, Esther J M Stoop, Eirikur Saeland, Ronald Vogels, Robert H E Friesen, Wouter Koudstaal, Jaap Goudsmit
Interactions with receptors for the Fc region of IgG (FcγRs) have been shown to contribute to the in vivo protection against influenza A viruses provided by broadly neutralizing antibodies (bnAbs) that bind to the viral hemagglutinin (HA) stem. In particular, Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) has been shown to contribute to protection by stem-binding bnAbs. Fc-mediated effector functions appear not to contribute to protection provided by strain-specific HA head-binding antibodies...
2016: Frontiers in Immunology
Tiziano Gaiotto, Simon E Hufton
Cross-neutralising monoclonal antibodies against influenza hemagglutinin (HA) are of considerable interest as both therapeutics and diagnostic tools. We have recently described five different single domain antibodies (nanobodies) which share this cross-neutralising activity and suggest their small size, high stability, and cleft binding properties may present distinct advantages over equivalent conventional antibodies. We have used yeast display in combination with deep mutational scanning to give residue level resolution of positions in the antibody-HA interface which are crucial for binding...
2016: PloS One
Satoru Yamasaki, Kanako Shimizu, Kohei Kometani, Maki Sakurai, Masami Kawamura, Shin-Ichiro Fujii
An induction of long-term cellular and humoral immunity is for the goal of vaccines, but the combination of antigens and adjuvant remain unclear. Here, we show, using a cellular vaccine carrying foreign protein antigen plus iNKT cell glycolipid antigen, designated as artificial adjuvant vector cells (aAVCs), that mature XCR1(-) DCs in situ elicit not only ordinal antigen-specific CD4(+)T cells, but also CD4(+) Tfh and germinal center, resulted in inducing long-term antibody production. As a mechanism for leading the long-term antibody production by aAVC, memory CD4(+) Tfh cells but not iNKTfh cells played an important role in a Bcl6 dependent manner...
October 14, 2016: Scientific Reports
Tatsufumi Usui, Kosuke Soda, Yukiko Tomioka, Hiroshi Ito, Toshiyo Yabuta, Hiroki Takakuwa, Koichi Otsuki, Toshihiro Ito, Tsuyoshi Yamaguchi
Since 2014, clade H5 subtype highly pathogenic avian influenza viruses (HPAIVs) have been distributed worldwide. These viruses, which were reported to be highly virulent in chickens by intravenous inoculation, have a consensus HPAI motif PLRERRRKR at the HA cleavage site. However, two-clade H5N8 viruses which we isolated from wild migratory birds in late 2014 in Japan possessed atypical HA cleavage sequences. A swan isolate, Tottori/C6, had a novel polybasic cleavage sequence, PLGERRRKR, and another isolate from a dead mandarin duck, Gifu/01, had a heterogeneous mixture of consensus PLRERRRKR and variant PLRERRRRKR sequences...
October 13, 2016: Virus Genes
(no author information available yet)
Avian influenza viruses affect both poultry production and public health. A subtype H5N8 (clade virus, following an outbreak in poultry in South Korea in January 2014, rapidly spread worldwide in 2014-2015. Our analysis of H5N8 viral sequences, epidemiological investigations, waterfowl migration, and poultry trade showed that long-distance migratory birds can play a major role in the global spread of avian influenza viruses. Further, we found that the hemagglutinin of clade virus was remarkably promiscuous, creating reassortants with multiple neuraminidase subtypes...
October 14, 2016: Science
Kuang-Po Li, Poa-Chun Chang, Ming-Chu Cheng, Duen-Huey Tan, Li-Hsuan Chen, Yu-Pin Liu, Yu-Ju Lin, Hsiang-Jung Tsai, Jui-Hung Shien
The sequence at the hemagglutinin (HA) cleavage site (CS) plays a key role in determining the pathogenicity of avian influenza viruses. Three types of HA CS sequences, QREKR/GL, QRKKR/GL and QRRKR/GL, were previously reported in Taiwanese H5N2 viruses that were isolated from chickens from 2003 to 2013. However, no HA CS sequence was reported for viruses isolated after 2013. This article presents the HA CS sequences and pathogenicity of H5N2 viruses that were isolated from chickens in Taiwan during 2013-2015...
October 3, 2016: Journal of Veterinary Medical Science
Xilong Kang, Yun Yang, Yang Jiao, Hongqin Song, Li Song, Dan Xiong, Lili Wu, Zhiming Pan, Xinan Jiao
In 2009, a novel pandemic swine-origin influenza A (H1N1) virus caused a public emergency of international concern. Vaccination is the primary strategy for the control of influenza epidemics. However, the poor immunopotency of many vaccine antigens is a major barrier to the development of effective vaccines against influenza. Flagellin, a Toll-like receptor 5 (TLR5) ligand, has been used as an adjuvant to enhance the immunopotency of vaccines in preclinical studies. Here, we developed a recombinant candidate vaccine, HA1-2-fljB, in which the globular head of the hemagglutinin (HA) antigen (residues 62-284) from H1N1 virus was fused genetically to the N-terminus of Salmonella typhimurium fljB...
October 8, 2016: Journal of Molecular Microbiology and Biotechnology
Claire D McWhite, Austin G Meyer, Claus O Wilke
Clinical influenza A virus isolates are frequently not sequenced directly. Instead, a majority of these isolates (~70% in 2015) are first subjected to passaging for amplification, most commonly in non-human cell culture. Here, we find that this passaging leaves distinct signals of adaptation, which can confound evolutionary analyses of the viral sequences. We find distinct patterns of adaptation to Madin-Darby (MDCK) and monkey cell culture absent from unpassaged hemagglutinin sequences. These patterns also dominate pooled datasets not separated by passaging type, and they increase in proportion to the number of passages performed...
July 2016: Virus Evolution
Ronan N Rouxel, Emilie Mérour, Stéphane Biacchesi, Michel Brémont
Novirhabdoviruses like Viral Hemorrhagic Septicemia Virus (VHSV) and Infectious Hematopoietic Necrosis Virus (IHNV) are fish-infecting Rhabdoviruses belonging to the Mononegavirales order. By reverse genetics, we previously showed that a recombinant VHSV expressing the West Nile Virus (WNV) E glycoprotein could serve as a vaccine platform against WNV. In the current study, we aimed to evaluate the potential of the Novirhabdovirus platform as a vaccine against influenza virus. Recombinant Novirhabdoviruses, rVHSV-HA and rIHNV-HA, expressing at the viral surface the hemagglutinin HA ectodomain were generated and used to immunized mice...
2016: PloS One
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