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Influenza hemagglutinin

Yoichiro Fujioka, Shinya Nishide, Toyoyuki Ose, Tadaki Suzuki, Izumi Kato, Hideo Fukuhara, Mari Fujioka, Kosui Horiuchi, Aya O Satoh, Prabha Nepal, Sayaka Kashiwagi, Jing Wang, Mika Horiguchi, Yuko Sato, Sarad Paudel, Asuka Nanbo, Tadaaki Miyazaki, Hideki Hasegawa, Katsumi Maenaka, Yusuke Ohba
Influenza A virus (IAV) infection is initiated by the attachment of the viral glycoprotein hemagglutinin (HA) to sialic acid on the host cell surface. However, the sialic acid-containing receptor crucial for IAV infection has remained unidentified. Here, we show that HA binds to the voltage-dependent Ca2+ channel Cav 1.2 to trigger intracellular Ca2+ oscillations and subsequent IAV entry and replication. IAV entry was inhibited by Ca2+ channel blockers (CCBs) or by knockdown of Cav 1.2. The CCB diltiazem also inhibited virus replication in vivo...
May 10, 2018: Cell Host & Microbe
Meiyue Wang, Zhenyu Zhang, Xiaojun Wang
Tetherin/BST-2/CD317 is an interferon-induced host restriction factor that can block the budding of enveloped viruses by tethering them to the cell surface. Many viruses use certain proteins to counteract restriction by tetherin from their natural hosts, but not from other species. The influenza A virus (FLUAV) has a wide range of subtypes with different host tropisms. Human tetherin (huTHN) has been reported to restrict only specific FLUAV strains and the viral hemagglutinin (HA) and neuraminidase (NA) genes determine the sensitivity to huTHN...
May 16, 2018: Viruses
Divya Venkatesh, Marjolein J Poen, Theo M Bestebroer, Rachel D Scheuer, Oanh Vuong, Mzia Chkhaidze, Anna Machablishvili, Jimsher Mamuchadze, Levan Ninua, Nadia B Fedorova, Rebecca A Halpin, Xudong Lin, Amy Ransier, Timothy B Stockwell, David E Wentworth, Divya Kriti, Jayeeta Dutta, Harm van Bakel, Anita Puranik, Marek J Slomka, Steve Essen, Ian H Brown, Ron A M Fouchier, Nicola S Lewis
Wild ducks and gulls are the major reservoirs for avian influenza A viruses (AIVs). The mechanisms that drive AIV evolution are complex at sites where various duck and gull species from multiple flyways breed, winter or stage. The Republic of Georgia is located at the intersection of three migratory flyways: Central Asian Flyway, East Asian/East African Flyway and Black Sea/Mediterranean Flyway. For six consecutive years (2010-2016), we collected AIV samples from various duck and gull species that breed, migrate and overwinter in Georgia...
May 16, 2018: Journal of Virology
Ping He, Guojun Wang, Yanning Mo, Qingxiong Yu, Xiong Xiao, Wenjuan Yang, Weifeng Zhao, Xuan Guo, Qiong Chen, Jianqiao He, Mingli Liang, Jian Zhu, Yangbao Ding, Zuzhang Wei, Kang Ouyang, Fang Liu, Hui Jian, Weijian Huang, Adolfo García-Sastre, Ying Chen
Considered a "mixing vessel" for influenza viruses, pigs can give rise to new influenza virus reassortants that can threaten humans. During our surveillance of pigs in Guangxi, China from 2013 to 2015, we isolated 11 H1N1 and three H3N2 influenza A viruses of swine origin (IAVs-S). Out of the 14, we detected ten novel triple-reassortant viruses, which contained surface genes (hemagglutinin and neuraminidase) from Eurasian avian-like (EA) H1N1 or seasonal human-like H3N2, matrix (M) genes from H1N1/2009 pandemic or EA H1N1, nonstructural (NS) genes from classical swine, and the remaining genes from H1N1/2009 pandemic...
May 16, 2018: Emerging Microbes & Infections
Xinrui Zhou, Jie Zheng, Fransiskus Xaverius Ivan, Rui Yin, Shoba Ranganathan, Vincent T K Chow, Chee-Keong Kwoh
BACKGROUND: Influenza viruses are undergoing continuous and rapid evolution. The fatal influenza A/H7N9 has drawn attention since the first wave of infections in March 2013, and raised more grave concerns with its increased potential to spread among humans. Experimental studies have revealed several host and virulence markers, indicating differential host binding preferences which can help estimate the potential of causing a pandemic. Here we systematically investigate the sequence pattern and structural characteristics of novel influenza A/H7N9 using computational approaches...
May 9, 2018: BMC Genomics
Katherine A Richards, John J Treanor, Jennifer L Nayak, Andrea J Sant
There is limited information on the antigen specificity and functional potential of the influenza-specific CD4 T cell repertoire in humans. Here, ELISPOT assays were used to examine circulating CD4 T cell influenza specificities directly ex vivo in healthy adults.  Our studies revealed CD4 T cell reactivity to multiple influenza proteins, including hemagglutinins, NA, M1 and NP. Unexpectedly, the immunodominance hierarchies and functional potential of cells reactive toward influenza A were distinct from influenza B...
May 12, 2018: Journal of Infectious Diseases
T M Babu, R Perera, J T Wu, T Fitzgerald, C Nolan, B J Cowling, S Krauss, J T Treanor, M Peiris
Introduction: Influenza A pandemics cause significant mortality and morbidity. H2N2 viruses have caused prior pandemic, and are circulating in avian reservoirs. The age-related frequency of current population immunity to H2 viruses was evaluated. Methods: Hemagglutinin inhibition (HAI) assays against historical human and recent avian influenza A (H2N2) viruses were performed across age groups in Rochester, NY and Hong Kong, China. The impact of existing cross-reactive HAI immunity on the effective reproductive number(R) was modeled...
May 12, 2018: Journal of Infectious Diseases
Akinlolu Jegede, Qigao Fu, Yohannes Berhane, Min Lin, Ashok Kumar, Jiewen Guan
The H9N2 strains of avian influenza viruses (AIVs) circulate worldwide in poultry and cause sporadic infection in humans. To better understand the evolution of these viruses while circulating in poultry, an H9N2 chicken isolate was passaged 19 times in chickens via aerosol inoculation. Whole-genome sequencing showed that the viruses from the initial stock and those after the 8th and 19th passages (P0, P8, and P19) all had the same monobasic cleavage site in the hemagglutinin (HA), typical for viruses of low pathogenicity...
April 2018: Canadian Journal of Veterinary Research, Revue Canadienne de Recherche Vétérinaire
Irina A Rudneva, Tatiana A Timofeeva, Evgenia A Mukasheva, Anna V Ignatieva, Aleksandr A Shilov, Elena I Burtseva, Boris I Timofeev, Nikolai V Kaverin
In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We investigated pH optimum of fusion, temperatures of HA heat inactivation, in vivo and in vitro replication kinetics, and connectivity with panel of sera of survivors patients in different epidemic seasons of the previously obtained influenza H1 escape mutants. Our results showed that N133D (H3 numbering) mutation significantly lowered the pH of fusion optimum. Several amino acid substitutions, including K163 N, Q192 L, D190E, G228E, and K285 M, reduced the stability of HA as determined by heat inactivation, whereas A198E substitution is associated with significant increase in HA thermostability compared to the wild-type virus...
May 10, 2018: Virus Research
Ya-Fang Wang, Chuan-Fa Chang, Huey-Pin Tsai, Chia-Yu Chi, Ih-Jen Su, Jen-Ren Wang
It is generally agreed that human influenza virus preferentially binds to α-2,6-linked sialic acid-containing receptors, and mutations that change the binding preference may alter virus infectivity and host tropism. Limited information is available on the glycan-binding specificity of epidemic influenza viruses. In this study, we systemically investigated the glycan-binding preferences of human influenza A(H3N2) viruses isolated from 1999 to 2007 in Taiwan using a high-throughput carbohydrate array. The binding patterns of 37 H3N2 viruses were classified into three groups with significant binding-pattern variations...
2018: PloS One
Yulia Desheva, Ivan Sychev, Tatiana Smolonogina, Andrey Rekstin, Natalia Ilyushina, Vladimir Lugovtsev, Anastasia Samsonova, Aleksey Go, Anna Lerner
The main objective of the study was to evaluate neuraminidase inhibiting (NI) antibodies against A/H1N1pdm09 influenza viruses in the community as a whole and after infection. We evaluated NI serum antibodies against A/California/07/09(H1N1)pdm and A/South Africa/3626/2013(H1N1)pdm in 134 blood donors of different ages using enzyme-linked lectin assay and in 15 paired sera from convalescents with laboratory confirmed influenza. The neuraminidase (NA) proteins of both A/H1N1pdm09 viruses had minimal genetic divergence, but demonstrated different enzymatic and antigenic properties...
2018: PloS One
Charlie S Bahnson, Rebecca L Poulson, Scott Krauss, Robert G Webster, David E Stallknecht
Influenza A virus (IAV) infections in shorebirds at Delaware Bay, New Jersey, USA, have historically included avian hemagglutinin (HA) subtypes H1-13, and H16. In a given year, infections are characterized by a limited number of HA and neuraminidase subtypes and a dominant HA subtype that often represents >50% of all isolates. Predominant HA subtypes shift between consecutive years. In addition, infection prevalence is consistently higher in Ruddy Turnstones ( Arenaria interpres morinella, RUTU) compared to Red Knots ( Calidris canutus rufa, REKN), despite comparable rates of exposure...
May 9, 2018: Journal of Wildlife Diseases
Sophie B Morgan, Barbara Holzer, Johanneke D Hemmink, Francisco J Salguero, John C Schwartz, Gloria Agatic, Elisabetta Cameroni, Barbara Guarino, Emily Porter, Pramila Rijal, Alain Townsend, Bryan Charleston, Davide Corti, Elma Tchilian
Influenza virus infection is a significant global health threat. Because of the lack of cross-protective universal vaccines, short time window during which antivirals are effective and drug resistance, new therapeutic anti-influenza strategies are required. Broadly, cross-protective antibodies that target conserved sites in the hemagglutinin (HA) stem region have been proposed as therapeutic agents. FI6 is the first proven such monoclonal antibody to bind to H1-H16 and is protective in mice and ferrets. Multiple studies have shown that Fc-dependent mechanisms are essential for FI6 in vivo efficacy...
2018: Frontiers in Immunology
Tianbo Zhang, Mengjie Xiao, Chun-Kwok Wong, Ka-Pun Chris Mok, Xin Zhao, Huihui Ti, Pang-Chui Shaw
BACKGROUND: Sheng Jiang San (SJS), a multi-herb formulation, is used in treating high fever, thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza nowadays. However, there is no evidence-based investigation and mechanism research to support the anti-influenza efficacy of SJS. This study aims at evaluating the anti-influenza effect of SJS and investigating its possible mechanism. METHODS: The inhibitory effect of SJS against different influenza virus strains on MDCK cells was examined...
May 8, 2018: BMC Complementary and Alternative Medicine
Giulietta Saletti, Thomas Gerlach, Guus F Rimmelzwaan
Currently used inactivated influenza vaccines aim at the induction of virus-neutralizing antibodies directed to the variable head domain of the viral hemagglutinin. Although these vaccines are effective against antigenically matching virus strains, they offer little protection against antigenically distinct drift variants or potentially pandemic viruses of alternative subtypes. In the last decades, the threat of novel influenza pandemics has sparked research efforts to develop vaccines that induce more broadly protective immunity...
May 4, 2018: Current Opinion in Immunology
Sarah F Andrews, Adrian B McDermott
One hundred years ago, the 1918 H1N1 Pandemic killed 20 million people worldwide. Despite the introduction of a worldwide surveillance system, large-scale production of influenza vaccines coupled with annual vaccination schemes, influenza remains a major public health concern. Prevention of influenza on a population basis requires intimate knowledge of the interplay between the virus' ability to escape the immune response and persistent recall and regeneration of the antibody response. Here we will briefly outline the nature of the antibody response, focusing on the response to intransigent regions of the hemagglutinin (HA) and speculate on the how this data may be used to inform and ultimately develop a universal influenza vaccine...
May 3, 2018: Current Opinion in Immunology
Rusheng Zhang, Dong Yao, Jingfang Chen, Wen Ye, Xinhua Ou, Tianmu Chen, Biancheng Sun
As of Aug 25, 2017, 17 incidences of human infection and 6 deaths due to the novel H5N6 virus have been reported in China. Genetic analysis of the viral genome revealed that this reassortant virus is highly pathogenic to poultry, and that the virus has a risk of transmission to humans. Accordingly, the development of a rapid, sensitive, and specific molecular diagnostic assay is critical for public health. In this study, a real-time reverse-transcription PCR (RT-PCR) assay was developed to specifically detect the novel H5N6 virus, with primer pairs targeting the hemagglutinin and neuraminidase gene sequences of this virus...
May 2, 2018: Journal of Virological Methods
Hideki Takahashi, Kazuki Misato, Taiki Aoshi, Yasuyuki Yamamoto, Yui Kubota, Xin Wu, Etsushi Kuroda, Ken J Ishii, Hirofumi Yamamoto, Yasuo Yoshioka
Vaccine adjuvants that can induce not only antigen-specific antibody responses but also Th1-type immune responses and CD8+ cytotoxic T lymphocyte responses are needed for the development of vaccines against infectious diseases and cancer. Of many available adjuvants, oligodeoxynucleotides (ODNs) with unmethylated cytosine-phosphate-guanine (CpG) motifs are the most promising for inducing the necessary immune responses, and these adjuvants are currently under clinical trials in humans. However, the development of novel delivery vehicles that enhance the adjuvant effects of CpG ODNs, subsequently increasing the production of cytokines such as type-I interferons (IFNs), is highly desirable...
2018: Frontiers in Immunology
Irina V Ilyina, Vladimir V Zarubaev, Irina N Lavrentieva, Anna A Shtro, Iana L Esaulkova, Dina V Korchagina, Sophia S Borisevich, Konstantin P Volcho, Nariman F Salakhutdinov
A set of (-)-isopulegol derived octahydro-2H-chromen-4-ols was synthesized and evaluated in vitro for antiviral activity against panel of reference influenza virus strains differing in subtype, origin (human or avian) and drug resistance. Compound (4R)-11a produced via one-pot synthesis by interaction between (-)-isopulegol and acetone was found to exhibit an outstanding activity against a number of H1N1 and H2N2 influenza virus strains with selectivity index more than 1500. (4R)-11a was shown to be most potent at early stages of viral cycle...
April 24, 2018: Bioorganic & Medicinal Chemistry Letters
L A Stepanova, R Y Kotlyarov, M A Shuklina, E A Blochina, M V Sergeeva, M V Potapchuk, A A Kovaleva, N V Ravin, L M Tsybalova
The ectodomain of the M2 protein (M2e) and the conserved fragment of the second subunit of hemagglutinin (HA2) are promising candidates for broadly protective vaccines. In this paper, we report on the design of chimeric constructs with differing orders of linkage of four tandem copies of M2e and the conserved fragment of HA2 (76-130) from phylogenetic group II influenza A viruses to the C-terminus of flagellin. The 3D-structure of two chimeric proteins showed that interior location of the M2e tandem copies (Flg-4M2e-HA2) provides partial α-helix formation nontypical of native M2e on the virion surface...
January 2018: Acta Naturae
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