scholarly journals In silico analysis of local RNA secondary structure in influenza virus A, B and C finds evidence of widespread ordered stability but little evidence of significant covariation

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Jake M. Peterson ◽  
Collin A. O’Leary ◽  
Walter N. Moss
Keyword(s):  
Influenza Virus ◽  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Influenza A ◽  
H1n1 Virus ◽  
In Silico Analysis ◽  
Rna Sequences ◽  
Local Secondary Structure ◽  
Infectious Cycle ◽  
Silico Analysis

AbstractInfluenza virus is a persistent threat to human health; indeed, the deadliest modern pandemic was in 1918 when an H1N1 virus killed an estimated 50 million people globally. The intent of this work is to better understand influenza from an RNA-centric perspective to provide local, structural motifs with likely significance to the influenza infectious cycle for therapeutic targeting. To accomplish this, we analyzed over four hundred thousand RNA sequences spanning three major clades: influenza A, B and C. We scanned influenza segments for local secondary structure, identified/modeled motifs of likely functionality, and coupled the results to an analysis of evolutionary conservation. We discovered 185 significant regions of predicted ordered stability, yet evidence of sequence covariation was limited to 7 motifs, where 3—found in influenza C—had higher than expected amounts of sequence covariation.

scholarly journals Exacerbation of Influenza Virus Infections in Mice by Intranasal Treatments and Implications for Evaluation of Antiviral Drugs

2012 ◽  
Vol 56 (12) ◽  
pp. 6328-6333 ◽  
Author(s):  
Donald F. Smee ◽  
Mark von Itzstein ◽  
Beenu Bhatt ◽  
E. Bart Tarbet
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
Antiviral Agent ◽  
Virus Production ◽  
Lung Pathology ◽  
Virus Infections ◽  
Challenge Dose ◽  
Virus Challenge ◽  
Time To Death

ABSTRACTCompounds lacking oral activity may be delivered intranasally to treat influenza virus infections in mice. However, intranasal treatments greatly enhance the virulence of such virus infections. This can be partially compensated for by giving reduced virus challenge doses. These can be 100- to 1,000-fold lower than infections without such treatment and still cause equivalent mortality. We found that intranasal liquid treatments facilitate virus production (probably through enhanced virus spread) and that lung pneumonia was delayed by only 2 days relative to a 1,000-fold higher virus challenge dose not accompanied by intranasal treatments. In one study, zanamivir was 90 to 100% effective at 10 mg/kg/day by oral, intraperitoneal, and intramuscular routes against influenza A/California/04/2009 (H1N1) virus in mice. However, the same compound administered intranasally at 20 mg/kg/day for 5 days gave no protection from death although the time to death was significantly delayed. A related compound, Neu5Ac2en (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid), was ineffective at 100 mg/kg/day. Intranasal zanamivir and Neu5Ac2en were 70 to 100% protective against influenza A/NWS/33 (H1N1) virus infections at 0.1 to 10 and 30 to 100 mg/kg/day, respectively. Somewhat more difficult to treat was A/Victoria/3/75 virus that required 10 mg/kg/day of zanamivir to achieve full protection. These results illustrate that treatment of influenza virus infections by the intranasal route requires consideration of both virus challenge dose and virus strain in order to avoid compromising the effectiveness of a potentially useful antiviral agent. In addition, the intranasal treatments were shown to facilitate virus replication and promote lung pathology.

scholarly journals Influenza virus segment 5 (+)RNA - secondary structure and new targets for antiviral strategies

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Marta Soszynska-Jozwiak ◽  
Paula Michalak ◽  
Walter N. Moss ◽  
Ryszard Kierzek ◽  
Julita Kesy ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Secondary Structure ◽  
Rna Secondary Structure ◽  
New Targets

scholarly journals Changes in RNA secondary structure affect NS1 protein expression during early stage influenza virus infection

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Irina Baranovskaya ◽  
Mariia Sergeeva ◽  
Artem Fadeev ◽  
Renata Kadirova ◽  
Anna Ivanova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Secondary Structure ◽  
Protein Expression ◽  
Rna Secondary Structure ◽  
Reverse Genetics ◽  
Early Stage ◽  
Influenza Virus Infection ◽  
Main Function ◽  
Ns1 Protein ◽  
Virus Strains

AbstractRNA secondary structures play a key role in splicing, gene expression, microRNA biogenesis, RNA editing, and other biological processes. The importance of RNA structures has been demonstrated in the life cycle of RNA-containing viruses, including the influenza virus. At least two regions of conserved secondary structure in NS segment (+) RNA are predicted to vary among influenza virus strains with respect to thermodynamic stability; both fall in the NS1 open reading frame. The NS1 protein is involved in multiple virus-host interaction processes, and its main function is to inhibit the cellular immune response to viral infection. Using a reverse genetics approach, four influenza virus strains were constructed featuring mutations that have different effects on RNA secondary structure. Growth curve experiments and ELISA data show that, at least in the first viral replication cycle, mutations G123A and A132G affecting RNA structure in the (82–148) NS RNA region influence NS1 protein expression.

HA1-2-fljB Vaccine Induces Immune Responses against Pandemic Swine-Origin H1N1 Influenza Virus in Mice

2016 ◽  
Vol 26 (6) ◽  
pp. 422-432 ◽  
Author(s):  
Xilong Kang ◽  
Yun Yang ◽  
Yang Jiao ◽  
Hongqin Song ◽  
Li Song ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
Candidate Vaccine ◽  
Major Barrier ◽  
Excellent Starting Point ◽  
Starting Point ◽  
Influenza A H1n1 ◽  
N Terminus

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 <i>Salmonella typhimurium</i> &#xFB02;jB. The recombinant HA1-2-fljB protein was expressed efficiently in<i> Escherichia coli</i>, and the immunogenicity and protective efficacy of recombinant HA1-2-fljB were evaluated in a mouse model. Immunization with HA1-2-fljB elicited robust IgG antibodies and neutralizing antibodies and completely protected the mice against infection by swine-origin influenza A/swine/Jangsu/38/2010 (H1N1). These results suggest that HA antigen placed at the N-terminus of flagellin is also an excellent starting point for creating a fusion HA1-2-fljB protein as a candidate vaccine, and the recombinant HA1-2-fljB protein will contribute to the development of a more effective vaccine against swine-origin influenza virus infection.

scholarly journals Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression

2015 ◽  
Vol 89 (10) ◽  
pp. 5651-5667 ◽  
Author(s):  
Daniel Dlugolenski ◽  
Les Jones ◽  
Elizabeth Howerth ◽  
David Wentworth ◽  
S. Mark Tompkins ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Influenza A ◽  
H1n1 Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Pandemic H1n1 ◽  
Human Influenza ◽  
Swine Virus ◽  
Virus Reassortment

ABSTRACTSwine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression.IMPORTANCEInfluenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment independent of differential sialic acid distribution. The findings also establish that circulating neuraminidase (NA) and PA genes could alter the pathogenic phenotype of the pandemic H1N1 virus, resulting in enhanced disease. The identification of such factors provides a framework for pandemic modeling and surveillance.

scholarly journals Using small samples to estimate neutral component size and robustness in the genotype–phenotype map of RNA secondary structure

2020 ◽  
Vol 17 (166) ◽  
pp. 20190784 ◽  
Author(s):  
Marcel Weiß ◽  
Sebastian E. Ahnert
Keyword(s):  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Point Mutations ◽  
Local Environment ◽  
Small Samples ◽  
Sequence Length ◽  
Rna Sequences ◽  
Component Size ◽  
Naturally Occurring ◽  
Non Coding Rna

In genotype–phenotype (GP) maps, the genotypes that map to the same phenotype are usually not randomly distributed across the space of genotypes, but instead are predominantly connected through one-point mutations, forming network components that are commonly referred to as neutral components (NCs). Because of their impact on evolutionary processes, the characteristics of these NCs, like their size or robustness, have been studied extensively. Here, we introduce a framework that allows the estimation of NC size and robustness in the GP map of RNA secondary structure. The advantage of this framework is that it only requires small samples of genotypes and their local environment, which also allows experimental realizations. We verify our framework by applying it to the exhaustively analysable GP map of RNA sequence length L = 15, and benchmark it against an existing method by applying it to longer, naturally occurring functional non-coding RNA sequences. Although it is specific to the RNA secondary structure GP map in the first place, our framework can probably be transferred and adapted to other sequence-to-structure GP maps.

scholarly journals Contemporary Seasonal Influenza A (H1N1) Virus Infection Primes for a More Robust Response To Split Inactivated Pandemic Influenza A (H1N1) Virus Vaccination in Ferrets

2010 ◽  
Vol 17 (12) ◽  
pp. 1998-2006 ◽  
Author(s):  
Ali H. Ellebedy ◽  
Thomas P. Fabrizio ◽  
Ghazi Kayali ◽  
Thomas H. Oguin ◽  
Scott A. Brown ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Seasonal Influenza ◽  
H1n1 Virus ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Inactivated Vaccine ◽  
H1n1 Influenza Virus ◽  
Influenza A H1n1

ABSTRACT Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.

In silico, Physico-chemical characterization and analysis of Sandalwood proteins

2018 ◽  
Vol 3 (02) ◽  
pp. 150-157
Author(s):  
Asad Amir ◽  
Neelesh Kapoor ◽  
Hirdesh Kumar ◽  
Mohd. Tariq ◽  
Mohd. Asif Siddiqui
Keyword(s):  
Secondary Structure ◽  
In Silico ◽  
Chemical Characterization ◽  
In Silico Analysis ◽  
Chemical Parameters ◽  
Physico Chemical ◽  
In Silico Studies ◽  
The Family ◽  
Silico Analysis

Sandalwood is a commercially and culturally important plant species belonging to the family Santalaceae and the genus Santalum. In Indian sandalwood is renowned for its oil, which is highly rated for its sweet, fragrant, persistent aroma and the fixative property which is highly demanded by the perfume industry. For better production and varieties, requires to understanding the functions of proteins, their analysis and characterization of proteins sequences and their structures, their localizations in cell and their interaction with other functional partner. Due to limited number of in silico studies on sandalwood, in the present study we have performed in silico analysis by characterization of sandalwood proteins. Total 23 proteins were obtained and characterization using UniProtKB, identifying their physico-chemical parameters using ProtParam tool and prediction of their secondary structure elements using GOR of all 23 proteins.

scholarly journals The Modified JiuWei QiangHuo Decoction Alleviated Severe Lung Injury Induced by H1N1 Influenza Virus by Regulating the NF-κB Pathway in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Lijuan Chen ◽  
Xin Yan ◽  
Qianlin Yan ◽  
Jiajun Fan ◽  
Hai Huang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Lung Injury ◽  
Influenza A ◽  
H1n1 Virus ◽  
Alternative Therapy ◽  
Severe Pneumonia ◽  
H1n1 Influenza ◽  
Influenza A H1n1 ◽  
Lung Injuries ◽  
Severe Lung

A new approach to treat infections of highly pathogenic influenza virus is to inhibit excessive innate immune response. JiuWei QiangHuo decoction has been used for centuries for the treatment of pulmonary disorders in China. In this study, we evaluated the anti-inflammatory activities of the modified JiuWei QiangHuo (MJWQH) decoction in the treatment of influenza A (H1N1) virus-induced severe pneumonia in mice. The results showed that MJWQH significantly increased the survival rate of H1N1-infected mice and suppressed the production of TNF-α, IL-1, IL-6, MCP-1, RANTES, and IFN-αon day 4 after infection. Moreover, oral administration of MJWQH efficiently inhibited virus replication and alleviated the severity of lung injuries. The results also showed that MJWQH may have potential therapeutic effect on severe lung injury induced by H1N1 virus by regulating the NF-κB pathway. Our study suggested that MJWQH might be an alternative therapy for the treatment of viral pneumonia.

scholarly journals In silico analysis and molecular characterization of Influenza A (H1N1) pdm09 virus circulating and causing major outbreaks in central India, 2009-2019

2020 ◽  
Author(s):  
Arshi Siddiqui ◽  
Rashmi Chowdhary ◽  
Harjeet Singh Maan ◽  
Sudhir Kumar Goel ◽  
Nidhi Tripathi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Vaccine Efficacy ◽  
Influenza A ◽  
In Silico Analysis ◽  
Central India ◽  
Gene Sequences ◽  
Ha Gene ◽  
Influenza A H1n1 ◽  
Silico Analysis

Background and Objectives: Influenza A/H1N1pdm09 causes respiratory illness and remains a concern for public health. Since its first emergence in 2009, the virus has been continuously circulating in the form of its genetic variants. Influenza A/ H1N1pdm09 surveillance is essential for uncovering emerging variants of epidemiologic and vaccine efficacy. The present study attempts in silico analysis and molecular characterization of Influenza A (H1N1) pdm09 virus circulating and causing major outbreaks in central India during 2009-2019. Materials and Methods: We have investigated the antigenic drift analysis of 96 isolates’ hemagglutinin (HA) gene sequences (59 central Indian and 37 local Indian and 28 global reference HA gene sequences) of Influenza A/H1N1pdm09 viruses from 2009 to 2019. The study includes mutational (Multiple sequence Alignment), phylogenetic (Maximum Likelihood Method), and statistical analysis (Covariance and correlation) of HA sequences submitted in NCBI, IRD and GISAID from central India. Results: Phylogenetic analysis indicated maximum clustering of central Indian HA gene sequences in genogroup 6B. Analysis of amino acid sequence alignment revealed changes in receptor binding site (RBS). The frequency of S220T amino acid substitution was found to be high followed by S202T, K300E A273T, K180Q. The Karl Pearson correlation coefficient (r) and covariance between the number of mutations and the death toll was found +0.246 and +100.3 respectively. Conclusion: The study identifies the continuous genetic variations in the HA gene sequences of circulating Influenza A/ H1N1pdm09 in central India from the year 2009 to 2019. Further suggesting importance of monitoring the gradual evolution of the virus with regards to an increase in virulence, pathogenicity and vaccine efficacy timely.

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