scholarly journals Clinically Relevant Influenza Virus Evolution Reconstituted in a Human Lung Airway-on-a-Chip

2021 ◽  
Author(s):  
Longlong Si ◽  
Haiqing Bai ◽  
Crystal Yuri Oh ◽  
Lei Jin ◽  
Rachelle Prantil-Baun ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Severe Acute Respiratory Syndrome ◽  
Human Lung ◽  
Viral Evolution ◽  
Rapid Evolution ◽  
Virus Evolution ◽  
Influenza Viruses ◽  
Epidemiological Factors ◽  
Global Evolution ◽  
Evolution Of Viruses

The rapid evolution of viruses, such as influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is challenging the use and development of antivirals and vaccines. Studies of within-host viral evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape viral global evolution as well as development of better antivirals and vaccines.

scholarly journals Mutation and Epistasis in Influenza Virus Evolution

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 407 ◽  
Author(s):  
Daniel Lyons ◽  
Adam Lauring
Keyword(s):  
Public Health ◽  
Influenza Virus ◽  
Vaccine Efficacy ◽  
Rapid Evolution ◽  
Evolutionary Process ◽  
Virus Evolution ◽  
Influenza Viruses ◽  
Antiviral Resistance ◽  
Epistatic Interactions ◽  
Public Health Challenge

Influenza remains a persistent public health challenge, because the rapid evolution of influenza viruses has led to marginal vaccine efficacy, antiviral resistance, and the annual emergence of novel strains. This evolvability is driven, in part, by the virus’s capacity to generate diversity through mutation and reassortment. Because many new traits require multiple mutations and mutations are frequently combined by reassortment, epistatic interactions between mutations play an important role in influenza virus evolution. While mutation and epistasis are fundamental to the adaptability of influenza viruses, they also constrain the evolutionary process in important ways. Here, we review recent work on mutational effects and epistasis in influenza viruses.

Triazavirin might be the new hope to fight Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

2021 ◽  
Vol 70 (1) ◽  
pp. 18-25
Author(s):  
Malík Ivan ◽  
Čižmárik Jozef ◽  
Kováč Gustáv ◽  
Pecháčová Mária ◽  
Hudecová Lucia
Keyword(s):  
Influenza Virus ◽  
Severe Acute Respiratory Syndrome ◽  
Rift Valley Fever Virus ◽  
Encephalitis Virus ◽  
Influenza Viruses ◽  
Swine Flu ◽  
Influenza B Virus ◽  
Influenza B ◽  
Antiviral Compound ◽  
Virus Influenza

Since the beginning of the outbreak, a large number of clinical trials have been registered worldwide, and thousands of drugs have been investigated to face new health emergency of highly contagious COVID-19 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Drug repurposing, i.e., utilizing an approved drug for a different indication, offers a time- and cost-efficient alternative for making new (relevant) therapies available to physicians and patients. Considering given strategy, many approved and investigational antiviral compounds, alone or in various relevant combinations, used in the past to fight Severe Acute Respiratory Syndrome Coronavirus-1, Middle East Respiratory Syndrome Coronavirus, Human Immunodeficiency Virus type 1, or Influenza viruses are being evaluated against the SARS-CoV-2. Triazavirin (TZV), a non-toxic broad--spectrum antiviral compound, is efficient against various strains of the Influenza A virus (Influenza Virus A, Orthomyxoviridae), i.e., swine flu (H1N1, or H3N2), avian influenza (H5N1, H5N2, H9N2, or highly pathogenic H7N3 strain), Influenza B virus (Influenza Virus B, Orthomyxoviridae), Respiratory Syncytial Virus (Orthopneumovirus, Pneumoviridae), Tick-Borne Encephalitis Virus (known as Forest-Spring Encephalitis Virus; Flavivirus, Flaviviridae), West Nile Virus (Flavivirus, Flavaviridae), Rift Valley Fever Virus (Phlebovirus, Bunyaviridae), and Herpes viruses (Simplexviruses, Herpesviridae) as well. In regard to COVID-19, the molecule probably reduced inflammatory reactions, thus limiting the damage to vital organs and reducing the need for therapeutic support, respectively. In addition, in silico computational methods indicated relatively satisfactory binding affinities of the TZV ligand to both structural (E)- and (S)-proteins, non-structural 3-chymotrypsin-like protease (3-CLpro) of SARS-CoV-2 as well as human angiotensin-I converting enzyme-2 (ACE-2). The interactions between TZV and given viral structures or the ACE-2 receptor for SARS-CoV-2 might effectively block both the entry of the pathogen into a host cell and its replication. Promising treatment patterns of COVID-19 positive patients might be also based on a suitable combination of a membrane fusion inhibitor (umifenovir, for example) with viral RNA synthesis and replication inhibitor (TZV).

scholarly journals Bayesian inference of antigenic and non-antigenic variables from haemagglutination inhibition assays for influenza surveillance

2018 ◽  
Vol 5 (7) ◽  
pp. 180113
Author(s):  
Emmanuel S. Adabor ◽  
Wilfred Ndifon
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Bayesian Method ◽  
Haemagglutination Inhibition ◽  
Virus Evolution ◽  
Influenza Viruses ◽  
Influenza Surveillance ◽  
Antigenic Properties ◽  
Analytical Work

Haemagglutination inhibition (HI) assays are typically used for comparing and characterizing influenza viruses. Data obtained from the assays (titres) are used quantitatively to determine antigenic differences between influenza strains. However, the use of these titres has been criticized as they sometimes fail to capture accurate antigenic differences between strains. Our previous analytical work revealed how antigenic and non-antigenic variables contribute to the titres. Building on this previous work, we have developed a Bayesian method for decoupling antigenic and non-antigenic contributions to the titres in this paper. We apply this method to a compendium of HI titres of influenza A (H3N2) viruses curated from 1968 to 2016. Remarkably, the results of this fit indicate that the non-antigenic variable, which is inversely correlated with viral avidity for the red blood cells used in HI assays, oscillates during the course of influenza virus evolution, with a period that corresponds roughly to the timescale on which antigenic variants replace each other. Together, the results suggest that the new Bayesian method is applicable to the analysis of long-term dynamics of both antigenic and non-antigenic properties of influenza virus.

scholarly journals Detection of severe acute respiratory syndrome coronavirus 2 and influenza viruses based on CRISPR-Cas12a

2020 ◽  
pp. 153537022096379
Author(s):  
Oraphan Mayuramart ◽  
Pattaraporn Nimsamer ◽  
Somruthai Rattanaburi ◽  
Naphat Chantaravisoot ◽  
Kritsada Khongnomnan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Severe Acute Respiratory Syndrome ◽  
Influenza A ◽  
Limit Of Detection ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Influenza Virus A ◽  
B Virus

Due to the common symptoms of COVID-19, patients are similar to influenza-like illness. Therefore, the detection method would be crucial to discriminate between SARS-CoV-2 and influenza virus-infected patients. In this study, CRISPR-Cas12a-based detection was applied for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus which would be a practical and attractive application for screening of patients with COVID-19 and influenza in areas with limited resources. The limit of detection for SARS-CoV-2, influenza A, and influenza B detection was 10, 103, and 103 copies/reaction, respectively. Moreover, the assays yielded no cross-reactivity against other respiratory viruses. The results revealed that the detection of influenza virus and SARS-CoV-2 by using RT-RPA and CRISPR-Cas12a technology reaches 96.23% sensitivity and 100% specificity for SARS-CoV-2 detection. The sensitivity for influenza virus A and B detections was 85.07% and 94.87%, respectively. In addition, the specificity for influenza virus A and B detections was approximately 96%. In conclusion, the RT-RPA with CRISPR-Cas12a assay was an effective method for the screening of influenza viruses and SARS-CoV-2 which could be applied to detect other infectious diseases in the future.

scholarly journals Linking influenza virus evolution within and between human hosts

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Katherine S Xue ◽  
Jesse D Bloom
Keyword(s):  
Influenza Virus ◽  
Evolutionary Dynamics ◽  
Global Scale ◽  
Influenza Viruses ◽  
Global Evolution ◽  
Synonymous Sites ◽  
Selection For ◽  
H3n2 Influenza ◽  
Human Infections ◽  
Individual Human

Abstract Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.

scholarly journals High Level of Genetic Compatibility between Swine-Origin H1N1 and Highly Pathogenic Avian H5N1 Influenza Viruses

2010 ◽  
Vol 84 (20) ◽  
pp. 10918-10922 ◽  
Author(s):  
Cássio Pontes Octaviani ◽  
Makoto Ozawa ◽  
Shinya Yamada ◽  
Hideo Goto ◽  
Yoshihiro Kawaoka
Keyword(s):  
Influenza Virus ◽  
H5n1 Virus ◽  
Human Lung ◽  
Cultured Cells ◽  
Influenza Viruses ◽  
Compatibility Studies ◽  
Genetic Compatibility ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
High Level

Reassortment is an important mechanism for the evolution of influenza viruses. Here, we coinfected cultured cells with the pandemic swine-origin influenza virus (S-OIV) and a contemporary H5N1 virus and found that these two viruses have high genetic compatibility. Studies of human lung cell lines indicated that some reassortants had better growth kinetics than their parental viruses. We conclude that reassortment between these two viruses can occur and could create pandemic H5N1 viruses.

scholarly journals Replication Dynamics, Pathogenicity, and Evolution of Influenza Viruses in Intestinal Caco-2 Cells

2020 ◽  
Author(s):  
Israa Elbashir ◽  
Heba Al Khatib ◽  
Hadi Yassine
Keyword(s):  
Influenza Virus ◽  
Virus Replication ◽  
Deep Sequencing ◽  
Virus Evolution ◽  
Influenza Viruses ◽  
Intestinal Cells ◽  
Sequencing Analysis ◽  
Influenza Virus Replication ◽  
Ha Protein ◽  
Deep Sequencing Analysis

Background: Influenza virus is a major cause of respiratory infections worldwide. Besides the common respiratory symptoms, namouras cases with gastrointestinal symptoms have been reported. Moreover, influenza virus has been detected in feces of up to 20.6 % of influenza-infected patients. Therefore, direct infection of intestinal cells with influenza virus is suspected; however, the mechanism of this infection has not been explored. AIM: To investigate influenza virus replication, cellular responses to infection, and virus evolution following serial infection in human Caucasian colon adenocarcinoma cells (Caco-2 cells). Method: Two influenza A subtypes (A/H3N2 and A/H1N1pdm 09) and one influenza B virus (B/Yamagata) were serially passaged in Caco-2. Quantitative PCR was used to study hormones and cytokines expression following infection. Deep sequencing analysis of viral genome was used to assess the virus evolution. Results: The replication capacity of the three viruses was maintained throughout 12 passages, with H3N2 virus being the fastest in adaptation. The expression of hormone and cytokines in Caco-2 cells was considerably different between the viruses and among the passages, however, a pattern of induction was observed at the late phase of infection. Deep sequencing analysis revealed a few amino acid substitutions in the HA protein of H3N2 and H1N1 viruses, mostly in the antigenic site. Moreover, virus evolution at the quasispecies level based on HA protein revealed that H3N2 and H1N1 harbored more diverse virus populations when compared to IBV, indicating their higher evolution within Caco-2 cells. Conclusion: The findings of this study indicate the possibility of influenza virus replication in intestinal cells. To further explain the gastrointestinal complications of influenza infections in-vivo experiments with different influenza viruses are needed.

scholarly journals Genetic and Pathobiologic Characterization of Pandemic H1N1 2009 Influenza Viruses from a Naturally Infected Swine Herd

2009 ◽  
Vol 84 (5) ◽  
pp. 2245-2256 ◽  
Author(s):  
Hana M. Weingartl ◽  
Yohannes Berhane ◽  
Tamiko Hisanaga ◽  
James Neufeld ◽  
Helen Kehler ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Viral Evolution ◽  
H1n1 Influenza ◽  
The United States ◽  
Human Case ◽  
Influenza Viruses ◽  
Viral Rna ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Live Virus

ABSTRACT Since its initial identification in Mexico and the United States, concerns have been raised that the novel H1N1 influenza virus might cause a pandemic of severity comparable to that of the 1918 pandemic. In late April 2009, viruses phylogenetically related to pandemic H1N1 influenza virus were isolated from an outbreak on a Canadian pig farm. This outbreak also had epidemiological links to a suspected human case. Experimental infections carried out in pigs using one of the swine isolates from this outbreak and the human isolate A/Mexico/InDRE4487/2009 showed differences in virus recovery from the lower respiratory tract. Virus was consistently isolated from the lungs of pigs infected with A/Mexico/InDRE4487/2009, while only one pig infected with A/swine/Alberta/OTH-33-8/2008 yielded live virus from the lung, despite comparable amounts of viral RNA and antigen in both groups of pigs. Clinical disease resembled other influenza virus infections in swine, albeit with somewhat prolonged virus antigen detection and delayed viral-RNA clearance from the lungs. There was also a noteworthy amount of genotypic variability among the viruses isolated from the pigs on the farm. This, along with the somewhat irregular pathobiological characteristics observed in experimentally infected animals, suggests that although the virus may be of swine origin, significant viral evolution may still be ongoing.

scholarly journals DAS181 Inhibits H5N1 Influenza Virus Infection of Human Lung Tissues

2009 ◽  
Vol 53 (9) ◽  
pp. 3935-3941 ◽  
Author(s):  
Renee W. Y. Chan ◽  
Michael C. W. Chan ◽  
Adam C. N. Wong ◽  
Rositsa Karamanska ◽  
Anne Dell ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Lung Tissue ◽  
Therapeutic Agent ◽  
Human Lung ◽  
Ex Vivo ◽  
Influenza Viruses ◽  
Human Lung Tissue

ABSTRACT DAS181 is a novel candidate therapeutic agent against influenza virus which functions via the mechanism of removing the virus receptor, sialic acid (Sia), from the adjacent glycan structures. DAS181 and its analogues have previously been shown to be potently active against multiple strains of seasonal and avian influenza virus strains in several experimental models, including cell lines, mice, and ferrets. Here we demonstrate that DAS181 treatment leads to desialylation of both α2-6-linked and α2-3-linked Sia in ex vivo human lung tissue culture and primary pneumocytes. DAS181 treatment also effectively protects human lung tissue and pneumocytes against the highly pathogenic avian influenza virus H5N1 (A/Vietnam/3046/2004). Two doses of DAS181 treatment given 12 h apart were sufficient to block H5N1 infection in the ex vivo lung tissue culture. These findings support the potential value of DAS181 as a broad-spectrum therapeutic agent against influenza viruses, especially H5N1.

Imported infectious respiratory disease

2007 ◽  
pp. 137-144
Keyword(s):  
Influenza Virus ◽  
Severe Acute Respiratory Syndrome ◽  
Avian Influenza ◽  
Respiratory Disease ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Species Barrier ◽  
Nasal Secretions

Avian influenza 138 Severe acute respiratory syndrome (SARS) 142 There are few avian influenza viruses that have crossed the species barrier to infect humans, all known cases of which have resulted from contact with infected birds. Infected birds shed influenza virus in saliva, nasal secretions, and faeces....

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