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human influenza challenge

Ioannis Sitaras, Xanthoula Rousou, Ben Peeters, Mart C M de Jong
BACKGROUND: Transmission of highly pathogenic avian influenza (HPAI) viruses in poultry flocks is associated with huge economic losses, culling of millions of birds, as well as human infections and deaths. In the cases where vaccination against avian influenza is used as a control measure, it has been found to be ineffective in preventing transmission of field strains. Reports suggest that one of the reasons for this is the use of vaccine doses much lower than the ones recommended by the manufacturer, resulting in very low levels of immunity...
October 8, 2016: Vaccine
Pranab Chatterjee, Manish Kakkar, Sanjay Chaturvedi
BACKGROUND: Globally, the threat of infectious diseases, particularly emerging infectious diseases, originating at the human-animal-environment interface, has caught health systems off guard. With forecasts that future pathogen emergence will be centred in hotspots in Asia, Africa, and Latin America, the need to prepare policy frameworks that can combat this threat is urgent. DISCUSSION: Emergence of diseases such as avian influenza and Ebola virus disease, which threatened social disruption, have established the need for intersectoral coordination/collaboration...
October 3, 2016: Infectious Diseases of Poverty
Jason R Wilson, Zhu Guo, Adrian Reber, Ram P Kamal, Nedzad Music, Shane Gansebom, Yaohui Bai, Min Levine, Paul Carney, Wen-Pin Tzeng, James Stevens, Ian A York
Zoonotic A(H7N9) avian influenza viruses emerged in China in 2013 and continue to be a threat to human public health, having infected over 800 individuals with a mortality rate approaching 40%. Treatment options for people infected with A(H7N9) include the use of neuraminidase (NA) inhibitors. However, like other influenza viruses, A(H7N9) can become resistant to these drugs. The use of monoclonal antibodies is a rapidly developing strategy for controlling influenza virus infection. Here we generated a murine monoclonal antibody (3c10-3) directed against the NA of A(H7N9) and show that prophylactic systemic administration of 3c10-3 fully protected mice from lethal challenge with wild-type A/Anhui/1/2013 (H7N9)...
October 3, 2016: Antiviral Research
Ying Sun, Chenghuai Yang, Junping Li, Ling Li, Minghui Cao, Qihong Li, Huijiao Li
H9 subtype avian influenza viruses (AIVs) remain a significant burden in the poultry industry and are considered to be one of the most likely causes of any new influenza pandemic in humans. As ducks play an important role in the maintenance of H9 viruses in nature, successful control of the spread of H9 AIVs in ducks will have significant beneficial effects on public health. Duck enteritis virus (DEV) may be a promising candidate viral vector for aquatic poultry vaccination. In this study, we constructed a recombinant DEV, rDEV-∆UL2-HA, inserting the hemagglutinin (HA) gene from duck-origin H9N2 AIV into the UL2 gene by homologous recombination...
October 5, 2016: Archives of Virology
Arti Vashist, Ajeet Kaushik, Atul Vashist, Rahul Dev Jayant, Asahi Tomitaka, Sharif Ahmad, Y K Gupta, Madhavan Nair
Since centuries, the rapid spread and cure of infectious diseases have been a major concern to the progress and survival of humans. These diseases are a global burden and the prominent cause for worldwide deaths and disabilities. Nanomedicine has emerged as the most excellent tool to eradicate and halt their spread. Various nanoformulations (NFs) using advanced nanotechnology are in demand. Recently, hydrogel and nanogel based drug delivery devices have posed new prospects to simulate the natural intelligence of various biological systems...
October 18, 2016: Biomaterials Science
Ashley Sobel Leonard, Micah T McClain, Gavin J D Smith, David Wentworth, Rebecca A Halpin, Xudong Lin, Amy Ransier, Timothy B Stockwell, Suman Das, Anthony S Gilbert, Robert Lambkin-Williams, Geoffrey S Ginsburg, Christopher W Woods, Katia Koelle
: Knowledge of influenza evolution at the point of transmission and at the intra-host level remains limited, particularly for human hosts. Here, we analyze a unique viral dataset of next-generation sequencing (NGS) samples generated from a human influenza challenge study wherein 17 healthy subjects were inoculated with egg-passaged virus. Nasal wash samples collected from 7 of these subjects were successfully deep sequenced. From these, we characterized changes in the subjects' viral populations during infection and identified differences between the virus in these samples and the viral stock used to inoculate the subjects...
October 5, 2016: Journal of Virology
Peter Pushko, Xiangjie Sun, Irina Tretyakova, Rachmat Hidajat, Joanna A Pulit-Penaloza, Jessica A Belser, Taronna R Maines, Terrence M Tumpey
Avian-origin influenza represents a global public health concern. In 2013, the H10N8 virus caused documented human infections for the first time. Currently, there is no approved vaccine against H10 influenza. Recombinant virus-like particles (VLPs) represent a promising vaccine approach. In this study, we evaluated H10 VLPs containing hemagglutinin from H10N8 virus as an experimental vaccine in a ferret challenge model. In addition, we evaluated quadri-subtype VLPs co-localizing H5, H7, H9 and H10 subtypes...
October 17, 2016: Vaccine
Wei Chen, Yandong Huang, Jana Shen
Proton-coupled transmembrane proteins play important roles in human health and diseases; however, detailed mechanisms are often elusive. Experimentally resolving proton positions and structural details is challenging, and conventional molecular dynamics simulations are performed with preassigned and fixed protonation states. To address this challenge, here we illustrate the use of the state-of-the-art continuous constant pH molecular dynamics (CpHMD) to directly describe the activation of the M2 channel of influenza virus, for which abundant experimental data are available...
October 6, 2016: Journal of Physical Chemistry Letters
Ying Fu, Zhen Zhang, Jared Sheehan, Yuval Avnir, Callie Ridenour, Thomas Sachnik, Jiusong Sun, M Jaber Hossain, Li-Mei Chen, Quan Zhu, Ruben O Donis, Wayne A Marasco
Understanding the natural evolution and structural changes involved in broadly neutralizing antibody (bnAb) development holds great promise for improving the design of prophylactic influenza vaccines. Here we report an haemagglutinin (HA) stem-directed bnAb, 3I14, isolated from human memory B cells, that utilizes a heavy chain encoded by the IGHV3-30 germline gene. MAb 3I14 binds and neutralizes groups 1 and 2 influenza A viruses and protects mice from lethal challenge. Analysis of VH and VL germline back-mutants reveals binding to H3 and H1 but not H5, which supports the critical role of somatic hypermutation in broadening the bnAb response...
2016: Nature Communications
David B Ettensohn, Mark W Frampton, Joan E Nichols, Norbert J Roberts
The current studies were undertaken to determine the susceptibility of human alveolar macrophages (AMs) to influenza A virus (IAV) infection in comparison with autologous peripheral blood-derived monocytes-macrophages (PBMs). AMs and PBMs were exposed to IAV in vitro and examined for their ability to bind and internalize IAV, and synthesize viral proteins and RNA. PBMs but not AMs demonstrated binding and internalization of the virus, synthesizing viral proteins and RNA. Exposure of AMs in the presence of a sialidase inhibitor or anti-IAV antibody resulted in viral protein synthesis by the cells...
September 6, 2016: Journal of Infectious Diseases
Larisa Rudenko, Leena Yeolekar, Irina Kiseleva, Irina Isakova-Sivak
Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987. In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP)...
October 26, 2016: Vaccine
J H Leibler, K Dalton, A Pekosz, G C Gray, E K Silbergeld
While technological advances in animal husbandry have facilitated increases in global meat production, the high density and geographic concentration of food animal production facilities pose risks of infectious disease transmission. The scale of the 2014-2015 highly pathogenic avian influenza H5N2 outbreak in the United States demonstrates the challenges in achieving pathogen control within and around industrial animal facilities using existing technologies. We discuss gaps in current practice in two specific systems within these facilities - ventilation and waste management - which are under-recognized as important drivers of microbial porosity...
September 4, 2016: Zoonoses and Public Health
Tao Cheng, Xiang Wang, Yufeng Song, Xinying Tang, Chao Zhang, Hongbo Zhang, Xia Jin, Dongming Zhou
Highly pathogenic avian H5N1 viruses may give rise to the next influenza pandemic due to their reassortment and mutation of the genome. Vaccine against this virus is important for coping with its potential threat. Chimpanzee adenovirus (Ad) vectors are a novel type of vaccine vectors that share the advantages of human serotype Ad vectors but without being affected by pre-existing human neutralizing antibody to the vaccine vector. Based on a replication-deficient chimpanzee Ad vector, AdC7, we generated a novel H5N1 vaccine candidate AdC7-H5HA that expresses H5N1 Hemagglutinin(HA)...
September 22, 2016: Vaccine
Tejabhiram Yadavalli, Deepak Shukla
Nanotechnology is increasingly playing important roles in various fields including virology. The emerging use of metal or metal oxide nanoparticles in virus targeting formulations shows the promise of improved diagnostic or therapeutic ability of the agents while uniquely enhancing the prospects of targeted drug delivery. Although a number of nanoparticles varying in composition, size, shape, and surface properties have been approved for human use, the candidates being tested or approved for clinical diagnosis and treatment of viral infections are relatively less in number...
August 26, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Florian I Schmidt, Leo Hanke, Benjamin Morin, Rebeccah Brewer, Vesna Brusic, Sean P J Whelan, Hidde L Ploegh
Manipulation of proteins is key in assessing their in vivo function. Although genetic ablation is straightforward, reversible and specific perturbation of protein function remains a challenge. Single domain antibody fragments, such as camelid-derived VHHs, can serve as inhibitors or activators of intracellular protein function, but functional testing of identified VHHs is laborious. To address this challenge, we have developed a lentiviral screening approach to identify VHHs that elicit a phenotype when expressed intracellularly...
2016: Nature Microbiology
Stacey M Hartwig, Margaret Ketterer, Michael A Apicella, Steven M Varga
Respiratory syncytial virus (RSV) and the common commensal and opportunistic pathogen, non-typeable Haemophilus influenzae (NTHi) both serve as a frequent cause of respiratory infection in children. Although it is well established that some respiratory viruses can increase host susceptibility to secondary bacterial infections, few studies have examined how commensal bacteria could influence a secondary viral response. Here, we examined the impact of NTHi exposure on a subsequent RSV infection of human bronchial epithelial cells (16HBE14o-)...
November 2016: Virology
Hannes Uchtenhagen, Cliff Rims, Gabriele Blahnik, I-Ting Chow, William W Kwok, Jane H Buckner, Eddie A James
MHC tetramers are an essential tool for characterizing antigen-specific CD4+ T cells. However, their ex vivo analysis is limited by the large sample requirements. Here we demonstrate a combinatorial staining approach that allows simultaneous characterization of multiple specificities to address this challenge. As proof of principle, we analyse CD4+ T-cell responses to the seasonal influenza vaccine, establishing a frequency hierarchy and examining differences in memory and activation status, lineage commitment and cytokine expression...
2016: Nature Communications
Claire M Smith, Paul D Scott, Christopher O'Callaghan, Andrew J Easton, Nigel J Dimmock
Defective interfering (DI) viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8) was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1); it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1...
2016: Viruses
Chunlin Huang, Xingwu Liu, Shiwei Sun, Shuai Cheng Li, Minghua Deng, Guangxue He, Haicang Zhang, Chao Wang, Yang Zhou, Yanlin Zhao, Dongbo Bu
In this study, we present representative human contact networks among Chinese college students. Unlike schools in the US, human contacts within Chinese colleges are extremely clustered, partly due to the highly organized lifestyle of Chinese college students. Simulations of influenza spreading across real contact networks are in good accordance with real influenza records; however, epidemic simulations across idealized scale-free or small-world networks show considerable overestimation of disease prevalence, thus challenging the widely-applied idealized human contact models in epidemiology...
2016: Scientific Reports
Hanjun Zhao, Hin Chu, Xiaoyu Zhao, Huiping Shuai, Bosco Ho-Yin Wong, Lei Wen, Shuofeng Yuan, Bo-Jian Zheng, Jie Zhou, Kwok-Yung Yuen
To evaluate the pathogenicity, a highly pathogenic avian influenza H7N7 virus (A/Netherlands/219/03) isolated from human was passaged in mice. A mutant virus (mH7N7) with attenuated virulence was isolated from mouse lung, which had a 3-log higher MLD50 than the wild-type virus (wH7N7). Sequence analysis and reverse genetics study revealed that mutations in PA account for the compromised viral replication in mammalian cells and mice. A mini-genome assay demonstrated that PA mutations P103H and S659L can cooperatively decrease polymerase activity...
November 2016: Virology
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