scholarly journals Arginine-rich histones have strong antiviral activity for influenza A viruses

2015 ◽  
Vol 21 (7) ◽  
pp. 736-745 ◽  
Author(s):  
Marloes Hoeksema ◽  
Shweta Tripathi ◽  
Mitchell White ◽  
Li Qi ◽  
Jeffery Taubenberger ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Influenza A Viruses ◽  
Strong Antiviral Activity

scholarly journals The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins

2013 ◽  
Vol 94 (1) ◽  
pp. 40-49 ◽  
Author(s):  
Shweta Tripathi ◽  
Tesfaldet Tecle ◽  
Anamika Verma ◽  
Erika Crouch ◽  
Mitchell White ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Epithelial Cells ◽  
Antiviral Activity ◽  
Influenza A ◽  
Density Lipoprotein ◽  
Surfactant Protein ◽  
Host Defence ◽  
Surfactant Protein D ◽  
Influenza A Viruses ◽  
Cationic Antimicrobial Peptide

LL-37, the only human cathelicidin, is a cationic antimicrobial peptide with antibacterial and antifungal activity. LL-37 is released from neutrophil granules and produced by epithelial cells. It has been implicated in host defence against influenza A virus (IAV) in recent studies. We now demonstrate dose-related neutralizing activity of LL-37 against several seasonal and mouse-adapted IAV strains. The ability of LL-37 to inhibit these IAV strains resulted mainly from direct effects on the virus, since pre-incubation of virus with LL-37 was needed for optimal inhibition. LL-37 bound high-density lipoprotein (HDL), and pre-incubation of LL-37 with human serum or HDL reduced its antiviral activity. LL-37 did not inhibit viral association with epithelial cells as assessed by quantitative RT-PCR or confocal microscopy. This finding contrasted with results obtained with surfactant protein D (SP-D). Unlike collectins or human neutrophil defensins (HNPs), LL-37 did not induce viral aggregation under electron microscopy. In the electron microscopy studies, LL-37 appeared to cause disruption of viral membranes. LL-37 had additive antiviral activity when combined with other innate inhibitors like SP-D, surfactant protein A and HNPs. Unlike HNPs, LL-37 did not bind SP-D significantly. These findings indicate that LL-37 contributes to host defence against IAV through a mechanism distinct from that of SP-D and HNPs.

scholarly journals Functional Comparison of Mx1 from Two Different Mouse Species Reveals the Involvement of Loop L4 in the Antiviral Activity against Influenza A Viruses

2015 ◽  
Vol 89 (21) ◽  
pp. 10879-10890 ◽  
Author(s):  
Judith Verhelst ◽  
Jan Spitaels ◽  
Cindy Nürnberger ◽  
Dorien De Vlieger ◽  
Tine Ysenbaert ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Influenza A Virus ◽  
Mus Musculus ◽  
Influenza A ◽  
Common Mechanism ◽  
Mus Spretus ◽  
Influenza A Viruses ◽  
Content Type ◽  
Mouse Species

ABSTRACTThe interferon-inducedMx1gene is an important part of the mammalian defense against influenza viruses.Mus musculusMx1 inhibits influenza A virus replication and transcription by suppressing the polymerase activity of viral ribonucleoproteins (vRNPs). Here, we compared the anti-influenza virus activity of Mx1 fromMus musculusA2G with that of its ortholog fromMus spretus. We found that the antiviral activity ofM. spretusMx1 was less potent than that ofM. musculusMx1. Comparison of theM. musculusMx1 sequence with theM. spretusMx1 sequence revealed 25 amino acid differences, over half of which were present in the GTPase domain and 2 of which were present in loop L4. However, thein vitroGTPase activity of Mx1 from the two mouse species was similar. Replacement of one of the residues in loop L4 inM. spretusMx1 by the corresponding residue of A2G Mx1 increased its antiviral activity. We also show that deletion of loop L4 prevented the binding of Mx1 to influenza A virus nucleoprotein and, hence, abolished the antiviral activity of mouse Mx1. These results indicate that loop L4 of mouse Mx1 is a determinant of antiviral activity. Our findings suggest that Mx proteins from different mammals use a common mechanism to inhibit influenza A viruses.IMPORTANCEMx proteins are evolutionarily conserved in vertebrates and inhibit a wide range of viruses. Still, the exact details of their antiviral mechanisms remain largely unknown. Functional comparison of theMxgenes from two species that diverged relatively recently in evolution can provide novel insights into these mechanisms. We show that bothMus musculusA2G Mx1 andMus spretusMx1 target the influenza virus nucleoprotein. We also found that loop L4 in mouse Mx1 is crucial for its antiviral activity, as was recently reported for primate MxA. This indicates that human and mouse Mx proteins, which have diverged by 75 million years of evolution, recognize and inhibit influenza A viruses by a common mechanism.

scholarly journals Mechanism of binding of surfactant protein D to influenza A viruses: importance of binding to haemagglutinin to antiviral activity

2000 ◽  
Vol 351 (2) ◽  
pp. 449-458 ◽  
Author(s):  
Kevan L. HARTSHORN ◽  
Mitchell R. WHITE ◽  
Dennis R. VOELKER ◽  
John COBURN ◽  
Ken ZANER ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Surfactant Protein ◽  
Systematic Evaluation ◽  
Surfactant Protein D ◽  
Globular Domain ◽  
Influenza A Viruses ◽  
Viral Neutralization ◽  
The Relationship ◽  
Haemagglutination Activity

Collectins are important in the initial containment of a variety of pathogens, including influenza A virus (IAV). We provide the first systematic evaluation of the oligosaccharide-binding sites for pulmonary surfactant protein D (SP-D) on specific IAV coat glycoproteins and define the relationship between this binding and antiviral activity. With the use of several techniques, SP-D was found to bind via its carbohydrate-recognition domain (CRD) to mannosylated, N-linked carbohydrates on the HA1 domain of the haemagglutinin (HA) and on the neuraminidase of IAV. Using a set of IAV strains that differed in the level and site of glycosylation, and a panel of recombinant collectins, we found that binding of SP-D to the globular domain of the HA was critical in mediating the inhibition of viral haemagglutination activity and infectivity. We also demonstrated that the pattern of binding of a collectin to IAV glycoproteins can be modified by altering the monosaccharide-binding affinity of its CRD or by linking the CRD to a different N-terminal/collagen domain. These studies clarify the mechanisms of viral neutralization by collectins and might be useful in engineering collectins for enhanced antiviral activity.

Evaluation of Multivalent Sialylated Polyglycerols for Resistance Induction in and Broad Antiviral Activity against Influenza A Viruses

2021 ◽  
Author(s):  
Marlena N. Stadtmueller ◽  
Sumati Bhatia ◽  
Pallavi Kiran ◽  
Malte Hilsch ◽  
Valentin Reiter-Scherer ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Influenza A Viruses ◽  
Resistance Induction

scholarly journals Antiviral Activity of the Human Cathelicidin, LL-37, and Derived Peptides on Seasonal and Pandemic Influenza A Viruses

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0124706 ◽  
Author(s):  
Shweta Tripathi ◽  
Guangshun Wang ◽  
Mitchell White ◽  
Li Qi ◽  
Jeffery Taubenberger ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Influenza A Viruses

scholarly journals Mutations flanking the carbohydrate binding site of surfactant protein D confer antiviral activity for pandemic influenza A viruses

2014 ◽  
Vol 306 (11) ◽  
pp. L1036-L1044 ◽  
Author(s):  
Nikolaos M. Nikolaidis ◽  
Mitchell R. White ◽  
Kimberly Allen ◽  
Shweta Tripathi ◽  
Li Qi ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Host Defense ◽  
Influenza A ◽  
Surfactant Protein ◽  
Viral Envelope ◽  
Surfactant Protein D ◽  
Carbohydrate Binding ◽  
Influenza A Viruses ◽  
Head Region ◽  
Pandemic Strains

We recently reported that a trimeric neck and carbohydrate recognition domain (NCRD) fragment of human surfactant protein D (SP-D), a host defense lectin, with combinatorial substitutions at the 325 and 343 positions (D325A+R343V) exhibits markedly increased antiviral activity for seasonal strains of influenza A virus (IAV). The NCRD binds to glycan-rich viral envelope proteins including hemagglutinin (HA). We now show that replacement of D325 with serine to create D325S+R343V provided equal or increased neutralizing activity compared with D325A+R343V. The activity of the double mutants was significantly greater than that of either single mutant (D325A/S or R343V). D325A+R343V and D325S+R343V also strongly inhibited HA activity, and markedly aggregated, the 1968 pandemic H3N2 strain, Aichi68. D325S+R343V significantly reduced viral loads and mortality of mice infected with Aichi68, whereas wild-type SP-D NCRD did not. The pandemic H1N1 strains of 1918 and 2009 have only one N-linked glycan side on the head region of the HA and are fully resistant to inhibition by native SP-D. Importantly, we now show that D325A+R343V and D325S+R343V inhibited Cal09 H1N1 and related strains, and reduced uptake of Cal09 by epithelial cells. Inhibition of Cal09 was mediated by the lectin activity of the NCRDs. All known human pandemic strains have at least one glycan attachment on the top or side of the HA head, and our results indicate that they may be susceptible to inhibition by modified host defense lectins.

Antiviral activity of the proteasome inhibitor VL-01 against influenza A viruses

2011 ◽  
Vol 91 (3) ◽  
pp. 304-313 ◽  
Author(s):  
Emanuel Haasbach ◽  
Eva-Katharina Pauli ◽  
Robert Spranger ◽  
David Mitzner ◽  
Ulrich Schubert ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Proteasome Inhibitor ◽  
Influenza A ◽  
Influenza A Viruses

scholarly journals Virucidal Activity of Moringa a From Moringa Oleifera Seeds Against Influenza A Viruses by Regulating TFEB

2020 ◽  
Author(s):  
Yongai Xiong ◽  
Muhammad Shahid Riaz Rajoka ◽  
MengXun Zhang ◽  
Ning Liang ◽  
Zhendan He
Keyword(s):  
Antiviral Activity ◽  
Inflammatory Cytokines ◽  
Influenza A ◽  
Moringa Oleifera ◽  
Cytopathic Effect ◽  
Cellular Protein ◽  
Host Cells ◽  
Influenza A Viruses ◽  
Different Types ◽  
Infected Cells

Abstract BackgroundInfluenza A viruses (IAVs) are highly contagious pathogens infecting human and numerous animals. The viruses cause millions of infection cases and thousands of deaths every year, thus making IAVs a continual threat to global health. MethodsMoringa A was isolated from Moringa oleifera seeds and tested for antiviral activity against H1N1. The antiviral activity of Moringa A was tested by checking their effect on hemagglutination and PFU activities of the studied virus, and the cytopathic effect was observed too. Additionally, the different types of treatment experiments were performed to complement the analysis of the antiviral activity of Moringa A, and the contents of inflammatory cytokines and the expression of TFEB were detected.ResultsMoringa A inhibits virus replication in host cells, and it protects infected cells from cytopathic effect induced by IAVs. The EC50 and EC90 value of Moringa A for IAVs were 1.27 and 5.30 μM, respectively. The different types of treatment experiments revealed that Moringa A has a significant inhibitory effect on the IAVs both before and after drug addition. What’s more, Moringa A was observed to decrease the levels of inflammatory cytokines TNF-α, IL-6, IL-1β and IFN-β in H1N1 infected RAW264.7 cells. Finaly, Moringa A was found to inhibit the expression and nuclear transfer of the cellular protein transcription factor EB (TFEB), and weaken the autophagy in infected cells, which could be an important antiviral mechnism of Moringa A. ConclusionsMoringa A has potent antiviral activity against IVAs, which could be due to the autophagy inhibition property.

Sign in / Sign up

Export Citation Format

Share Document