scholarly journals Wipes Coated with a Singlet-Oxygen-Producing Photosensitizer Are Effective against Human Influenza Virus but Not against Norovirus

2014 ◽  
Vol 80 (14) ◽  
pp. 4391-4397 ◽  
Author(s):  
Katharina Verhaelen ◽  
Martijn Bouwknegt ◽  
Saskia Rutjes ◽  
Ana Maria de Roda Husman ◽  
Erwin Duizer
Keyword(s):  
Public Health ◽  
Influenza Virus ◽  
Health Risk ◽  
Singlet Oxygen ◽  
Human Adenovirus ◽  
Influenza Viruses ◽  
Murine Norovirus ◽  
Human Influenza ◽  
Human Influenza Virus ◽  
Public Health Risk

ABSTRACTTransmission of enteric and respiratory viruses, including human norovirus (hNoV) and human influenza virus, may involve surfaces. In food preparation and health care settings, surfaces are cleaned with wipes; however, wiping may not efficiently reduce contamination or may even spread viruses, increasing a potential public health risk. The virucidal properties of wipes with a singlet-oxygen-generating immobilized photosensitizer (IPS) coating were compared to those of similar but uncoated wipes (non-IPS) and of commonly used viscose wipes. Wipes were spiked with hNoV GI.4 and GII.4, murine norovirus 1 (MNV-1), human adenovirus type 5 (hAdV-5), and influenza virus H1N1 to study viral persistence. We also determined residual and transferred virus proportions on steel carriers after successively wiping a contaminated and an uncontaminated steel carrier. On IPS wipes only, influenza viruses were promptly inactivated with a 5-log10reduction.Dvalues of infectious MNV-1 and hAdV-5 were 8.7 and 7.0 h on IPS wipes, 11.6 and 9.3 h on non-IPS wipes, and 10.2 and 8.2 h on viscose wipes, respectively. Independently of the type of wipe, dry cleaning removed, or drastically reduced, initial spot contamination of hNoV on surfaces. All wipes transferred hNoV to an uncontaminated carrier; however, the risk of continued transmission by reuse of wipes after 6 and 24 h was limited for all viruses. We conclude that cleaning wet spots with dry wipes efficiently reduced spot contamination on surfaces but that cross-contamination with noroviruses by wiping may result in an increased public health risk at high initial virus loads. For influenza virus, IPS wipes present an efficient one-step procedure for cleaning and disinfecting contaminated surfaces.

scholarly journals Positive Selection in CD8+T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages

2015 ◽  
Vol 89 (22) ◽  
pp. 11275-11283 ◽  
Author(s):  
Heather M. Machkovech ◽  
Trevor Bedford ◽  
Marc A. Suchard ◽  
Jesse D. Bloom
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Positive Selection ◽  
Swine Influenza ◽  
Selective Advantage ◽  
Influenza Viruses ◽  
T Cell Epitopes ◽  
Human Influenza ◽  
Human Influenza Virus

ABSTRACTNumerous experimental studies have demonstrated that CD8+T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+T cells. Here we use a novel computational approach to test for selection in CD8+T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.IMPORTANCEThere is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8+T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal models and are associated with decreased symptoms in humans, no studies have proven with statistical significance that influenza virus evolves under positive selection to escape T cells. Here we use comparisons of human and swine influenza viruses to rigorously demonstrate that human influenza virus evolves under pressure to fix mutations in the nucleoprotein that promote escape from T cells. We further show that viruses with these mutations have a selective advantage since they are preferentially located on the “trunk” of the phylogenetic tree. Overall, our results show that CD8+T cells targeting nucleoprotein play an important role in shaping influenza virus evolution.

scholarly journals Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses

2016 ◽  
Vol 90 (24) ◽  
pp. 11157-11167 ◽  
Author(s):  
Xiangjie Sun ◽  
Hui Zeng ◽  
Amrita Kumar ◽  
Jessica A. Belser ◽  
Taronna R. Maines ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Avian Influenza ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Human Influenza ◽  
Avian Influenza Viruses ◽  
Human Influenza Virus ◽  
Pulmonary Endothelial Cells

ABSTRACTA role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans.IMPORTANCEAvian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary endothelial damage are known to be present during severe human infections, the role of pulmonary endothelial cells in the pathogenesis of avian influenza virus infections is largely unknown. By comparing human seasonal influenza strains to avian influenza viruses, we provide greater insight into the interaction of influenza virus with human pulmonary endothelial cells. We show that human influenza virus infection is blocked during the early stages of virus entry, which is likely due to the relatively high expression of the host antiviral factors IFITMs (interferon-induced transmembrane proteins) located in membrane-bound compartments inside cells. Overall, this study provides a mechanism by which human endothelial cells limit replication of human influenza virus strains, whereas avian influenza viruses overcome these restriction factors in this cell type.

scholarly journals Guinea Pig Model for Evaluating the Potential Public Health Risk of Swine and Avian Influenza Viruses

PLoS ONE ◽  
2010 ◽  
Vol 5 (11) ◽  
pp. e15537 ◽  
Author(s):  
Yipeng Sun ◽  
Yuhai Bi ◽  
Juan Pu ◽  
Yanxin Hu ◽  
Jingjing Wang ◽  
...  
Keyword(s):  
Public Health ◽  
Avian Influenza ◽  
Guinea Pig ◽  
Health Risk ◽  
Influenza Viruses ◽  
Pig Model ◽  
Avian Influenza Viruses ◽  
Public Health Risk ◽  
Guinea Pig Model ◽  
Potential Public Health

Public Health Risk from Avian Influenza Viruses

2005 ◽  
Vol 49 (3) ◽  
pp. 317-327 ◽  
Author(s):  
Michael L. Perdue ◽  
David E. Swayne
Keyword(s):  
Public Health ◽  
Avian Influenza ◽  
Health Risk ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Public Health Risk

scholarly journals IMMUNOLOGICAL RELATIONSHIP BETWEEN THE SWINE AND HUMAN INFLUENZA VIRUSES IN SWINE

1937 ◽  
Vol 66 (2) ◽  
pp. 151-168 ◽  
Author(s):  
Richard E. Shope
Keyword(s):  
Influenza Virus ◽  
Influenza Infection ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Human Influenza ◽  
Human Influenza Virus ◽  
Immunological Relationship ◽  
Cross Immunity ◽  
The Cross

Swine recovered from infection with either swine influenza or swine influenza virus alone are usually not only immune but refractory to human influenza infection. Swine recovered from infection with a mixture of human influenza virus and H. influenzae suis are usually immune to swine influenza while those recovered from infection with human influenza virus alone are usually not immune to swine influenza. The possible mechanisms involved in the cross-immunity between the influenza viruses are discussed.

scholarly journals Resistance to Neuraminidase Inhibitors Conferred by an R292K Mutation in a Human Influenza Virus H7N9 Isolate Can Be Masked by a Mixed R/K Viral Population

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
H.-L. Yen ◽  
J. L. McKimm-Breschkin ◽  
K.-T. Choy ◽  
D. D. Y. Wong ◽  
P. P. H. Cheung ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Mixed Population ◽  
Influenza Viruses ◽  
Viral Population ◽  
The Novel ◽  
Inhibition Assay ◽  
Human Influenza ◽  
Wild Type ◽  
Oseltamivir Carboxylate ◽  
Human Influenza Virus

ABSTRACTWe characterized the A/Shanghai/1/2013 virus isolated from the first confirmed human case of A/H7N9 disease in China. The A/Shanghai/1/2013 isolate contained a mixed population of R (65%; 15/23 clones) and K (35%; 8/23 clones) at neuraminidase (NA) residue 292, as determined by clonal sequencing. A/Shanghai/1/2013 with mixed R/K at residue 292 exhibited a phenotype that is sensitive to zanamivir and oseltamivir carboxylate by the enzyme-based NA inhibition assay. The plaque-purified A/Shanghai/1/2013 with dominant K292 (94%; 15/16 clones) showed sensitivity to zanamivir that had decreased by >30-fold and to oseltamivir carboxylate that had decreased by >100-fold compared to its plaque-purified wild-type counterpart possessing dominant R292 (93%, 14/15 clones). In Madin-Darby canine kidney (MDCK) cells, the plaque-purified A/Shanghai/1/2013-NAK292virus exhibited no reduction in viral titer under conditions of increasing concentrations of oseltamivir carboxylate (range, 0 to 1,000 µM) whereas the replication of the plaque-purified A/Shanghai/1/2013-NAR292and the A/Shanghai/2/2013 viruses was completely inhibited at 250 µM and 31.25 µM of oseltamivir carboxylate, respectively. Although the plaque-purified A/Shanghai/1/2013-NAK292virus exhibited lower NA enzyme activity and a higherKmfor 2′-(4-methylumbelliferryl)-α-d-N-acetylneuraminic acid than the wild-type A/Shanghai/1/2013-NAR292virus, the A/Shanghai/1/2013-NAK292virus formed large plaques and replicated efficientlyin vitro. Our results confirmed that the NA R292K mutation confers resistance to oseltamivir, peramivir, and zanamivir in the novel human H7N9 viruses. Importantly, detection of the resistance phenotype may be masked in the clinical samples containing a mixed population of R/K at NA residue 292 in the enzyme-based NA inhibition assay.IMPORTANCEThe neuraminidase (NA) inhibitors oseltamivir and zanamivir are currently the front-line therapeutic options against the novel H7N9 influenza viruses, which possess an S31N mutation that confers resistance to the M2 ion channel blockers. It is therefore important to evaluate the sensitivity of the clinical isolates to NA inhibitors and to monitor for the emergence of resistant variants. We characterized the A/Shanghai/1/2013 (H7N9) isolate which contained a mixed population of R/K at NA residue 292. While the clinical isolate exhibited a phenotype of sensitivity to NA inhibitors using the enzyme-based NA inhibition assay, the plaque-purified A/Shanghai/1/2013 virus with dominant K292 was resistant to zanamivir, peramivir, and oseltamivir. Resistance to NA inhibitors conferred by the R292K mutation in a human influenza virus H7N9 isolate can be masked by a mixed R/K viral population, and this should be taken into consideration while monitoring antiviral resistance in patients with H7N9 infection.

Reassortment ability of the 2009 pandemic H1N1 influenza virus with circulating human and avian influenza viruses: Public health risk implications

2013 ◽  
Vol 175 (2) ◽  
pp. 151-154 ◽  
Author(s):  
Maria Stincarelli ◽  
Rosaria Arvia ◽  
Maria Alessandra De Marco ◽  
Valeria Clausi ◽  
Fabiana Corcioli ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza Virus ◽  
Avian Influenza ◽  
Health Risk ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Avian Influenza Viruses ◽  
Pandemic H1n1 Influenza

scholarly journals NEUTRALIZATION TESTS WITH SERA OF CONVALESCENT OR IMMUNIZED ANIMALS AND THE VIRUSES OF SWINE AND HUMAN INFLUENZA

1936 ◽  
Vol 63 (5) ◽  
pp. 645-653 ◽  
Author(s):  
Thomas Francis ◽  
Richard E. Shope
Keyword(s):  
Influenza Virus ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Human Influenza ◽  
Human Influenza Virus ◽  
Neutralizing Capacity ◽  
Heterologous Virus

Human and swine influenza viruses were regularly neutralized by their homologous immune sera. However, the sera of animals convalescent from infection with either the swine or human influenza virus possessed little, if any, neutralizing capacity for the heterologous virus. Hyperimmunization of animals against swine influenza virus tended to increase the neutralizing capacity of their sera for human influenza virus, but in an inconstant fashion, whereas repeated inoculations with human influenza virus frequently resulted in sera with strong neutralizing activities against swine influenza virus. These observations serve to emphasize both the immunological distinctiveness and the interrelationships of swine and human influenza viruses.

scholarly journals Attenuation of Equine Influenza Viruses through Truncations of the NS1 Protein

2005 ◽  
Vol 79 (13) ◽  
pp. 8431-8439 ◽  
Author(s):  
Michelle Quinlivan ◽  
Dmitriy Zamarin ◽  
Adolfo García-Sastre ◽  
Ann Cullinane ◽  
Thomas Chambers ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Mdck Cells ◽  
Influenza Viruses ◽  
Common Disease ◽  
Ns1 Protein ◽  
Human Influenza ◽  
Equine Influenza Virus ◽  
Human Influenza Virus ◽  
Equine Influenza

ABSTRACT Equine influenza is a common disease of the horse, causing significant morbidity worldwide. Here we describe the establishment of a plasmid-based reverse genetics system for equine influenza virus. Utilizing this system, we generated three mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have previously shown that a recombinant human influenza virus lacking the NS1 gene (delNS1) could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 protein is responsible for IFN antagonist activity. Contrary to previous findings with human influenza virus, we found that in the case of equine influenza virus, the length of the NS1 protein did not correlate with the level of attenuation of that virus. With equine influenza virus, the mutant virus with the shortest NS1 protein turned out to be the least attenuated. We speculate that the basis for attenuation of the equine NS1 mutant viruses generated is related to their level of NS1 protein expression. Our findings show that the recombinant mutant viruses are impaired in their ability to inhibit IFN production in vitro and they do not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in MDCK cells, or in vivo in a mouse model. Therefore, these attenuated mutant NS1 viruses may have potential as candidates for a live equine influenza vaccine.

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