The antiviral resistance of influenza virus

Therapy ◽  
2011 ◽  
Vol 8 (6) ◽  
pp. 741-762 ◽  
Author(s):  
Vanessa Escuret ◽  
Olivier Ferraris ◽  
Bruno Lina
Keyword(s):  
Influenza Virus ◽  
Antiviral Resistance

scholarly journals Antiviral resistance markers in influenza virus sequences in Mexico, 2000–2017

2018 ◽  
Vol Volume 11 ◽  
pp. 1751-1756 ◽  
Author(s):  
William Toledo-Rueda ◽  
Nora H Rosas-Murrieta ◽  
José Esteban Muñoz-Medina ◽  
César González-Bonilla ◽  
Julio Reyes-Leyva ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Resistance ◽  
Resistance Markers

scholarly journals Influenza Virus: Small Molecule Therapeutics and Mechanisms of Antiviral Resistance

2019 ◽  
Vol 25 (38) ◽  
pp. 5115-5127 ◽  
Author(s):  
Julianna Han ◽  
Jasmine Perez ◽  
Adam Schafer ◽  
Han Cheng ◽  
Norton Peet ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Small Molecule ◽  
Virus Disease ◽  
The Elderly ◽  
Significant Loss ◽  
Influenza Viruses ◽  
Antiviral Resistance ◽  
Novel Therapeutics ◽  
Seasonal Epidemics ◽  
Small Molecule Therapeutics

Background: Influenza viruses cause severe upper respiratory illness in children and the elderly during seasonal epidemics. Influenza viruses from zoonotic reservoirs can also cause pandemics with significant loss of life in all age groups. Although vaccination is one of the most effective methods to protect against seasonal epidemics, seasonal vaccines vary in efficacy, can be ineffective in the elderly population, and do not provide protection against novel strains. Small molecule therapeutics are a critical part of our antiviral strategies to control influenza virus epidemics and pandemics as well as to ameliorate disease in elderly and immunocompromised individuals. Objective: This review aims to summarize the existing antiviral strategies for combating influenza viruses, the mechanisms of antiviral resistance for available drugs, and novel therapeutics currently in development. Methods: We systematically evaluated and synthesized the published scientific literature for mechanistic detail into therapeutic strategies against influenza viruses. Results: Current IAV strains have developed resistance to neuraminidase inhibitors and nearly complete resistance to M2 ion channel inhibitors, exacerbated by sub-therapeutic dosing used for treatment and chemoprophylaxis. New tactics include novel therapeutics targeting host components and combination therapy, which show potential for fighting influenza virus disease while minimizing viral resistance. Conclusion: Antiviral drugs are crucial for controlling influenza virus disease burden, but their efficacy is limited by human misuse and the capacity of influenza viruses to circumvent antiviral barriers. To relieve the public health hardship of influenza virus, emerging therapies must be selected for their capacity to impede not only influenza virus disease, but also the development of antiviral resistance.

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.

scholarly journals INFLUENZA VIRUS SURVEILLANCE BY THE INSTITUTO ADOLFO LUTZ, INFLUENZA SEASON 2014: ANTIVIRAL RESISTANCE

2015 ◽  
Vol 57 (1) ◽  
pp. 92-92
Author(s):  
Katia Corrêa de Oliveira Santos ◽  
Daniela Bernardes Borges da Silva ◽  
Margarete Aparecida Benega ◽  
Renato de Sousa Paulino ◽  
Elian Reis E Silva Jr ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza Season ◽  
Antiviral Resistance ◽  
Virus Surveillance

scholarly journals The Discovery of the Antiviral Resistance GeneMx: A Story of Great Ideas, Great Failures, and Some Success

2018 ◽  
Vol 5 (1) ◽  
pp. 33-51 ◽  
Author(s):  
Otto Haller ◽  
Heinz Arnheiter ◽  
Jovan Pavlovic ◽  
Peter Staeheli
Keyword(s):  
Influenza Virus ◽  
Antiviral Resistance ◽  
Innate Resistance ◽  
Interferon Stimulated Genes ◽  
Pure Chance ◽  
New View

The discovery of the Mx gene–dependent, innate resistance of mice against influenza virus was a matter of pure chance. Although the subsequent analysis of this antiviral resistance was guided by straightforward logic, it nevertheless led us into many blind alleys and was full of surprising turns and twists. Unexpectedly, this research resulted in the identification of one of the first interferon-stimulated genes and provided a new view of interferon action. It also showed that in many species, MX proteins have activities against a broad range of viruses. To this day, Mx research continues to flourish and to provide insights into the never-ending battle between viruses and their hosts.

Antiviral resistance of influenza virus in the season 2014/15 in Denmark

2015 ◽  
Vol 70 ◽  
pp. S47
Author(s):  
R. Trebbien ◽  
K. Vorborg ◽  
J. Rønn ◽  
C.B. Christiansen ◽  
M.K. Thomsen ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Resistance

Are R292K, E119V and I222L substitutions associated with antiviral resistance in all Influenza virus subtypes within group 2 neuraminidases (N3, N6, N7, and N9)?

2015 ◽  
Vol 70 ◽  
pp. S46
Author(s):  
A. Gaymard ◽  
C. Aymeric ◽  
M. Sabatier ◽  
Michèle Ottmann ◽  
B. Lina ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Resistance ◽  
Group 2

scholarly journals Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Rebecca Frise ◽  
Konrad Bradley ◽  
Neeltje van Doremalen ◽  
Monica Galiano ◽  
Ruth A. Elderfield ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Resistance ◽  
Contact Transmission ◽  
Droplet Transmission

scholarly journals Intrahost Dynamics of Antiviral Resistance in Influenza A Virus Reflect Complex Patterns of Segment Linkage, Reassortment, and Natural Selection

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Matthew B. Rogers ◽  
Timothy Song ◽  
Robert Sebra ◽  
Benjamin D. Greenbaum ◽  
Marie-Eve Hamelin ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Influenza Virus ◽  
Natural Selection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Antiviral Resistance ◽  
Human Influenza ◽  
Individual Host ◽  
Complex Patterns

ABSTRACT Resistance following antiviral therapy is commonly observed in human influenza viruses. Although this evolutionary process is initiated within individual hosts, little is known about the pattern, dynamics, and drivers of antiviral resistance at this scale, including the role played by reassortment. In addition, the short duration of human influenza virus infections limits the available time window in which to examine intrahost evolution. Using single-molecule sequencing, we mapped, in detail, the mutational spectrum of an H3N2 influenza A virus population sampled from an immunocompromised patient who shed virus over a 21-month period. In this unique natural experiment, we were able to document the complex dynamics underlying the evolution of antiviral resistance. Individual resistance mutations appeared weeks before they became dominant, evolved independently on cocirculating lineages, led to a genome-wide reduction in genetic diversity through a selective sweep, and were placed into new combinations by reassortment. Notably, despite frequent reassortment, phylogenetic analysis also provided evidence for specific patterns of segment linkage, with a strong association between the hemagglutinin (HA)- and matrix (M)-encoding segments that matches that previously observed at the epidemiological scale. In sum, we were able to reveal, for the first time, the complex interaction between multiple evolutionary processes as they occur within an individual host. IMPORTANCE Understanding the evolutionary forces that shape the genetic diversity of influenza virus is crucial for predicting the emergence of drug-resistant strains but remains challenging because multiple processes occur concurrently. We characterized the evolution of antiviral resistance in a single persistent influenza virus infection, representing the first case in which reassortment and the complex patterns of drug resistance emergence and evolution have been determined within an individual host. Deep-sequence data from multiple time points revealed that the evolution of antiviral resistance reflects a combination of frequent mutation, natural selection, and a complex pattern of segment linkage and reassortment. In sum, these data show how immunocompromised hosts may help reveal the drivers of strain emergence.

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