scholarly journals Structures and functions linked to genome-wide adaptation of human influenza A viruses

2018 ◽  
Author(s):  
Thorsten R. Klingen ◽  
Jens Loers ◽  
Stephanie Stanelle-Bertram ◽  
Gülsah Gabriel ◽  
Alice C. McHardy
Keyword(s):  
Influenza A ◽  
Inflammatory Responses ◽  
Respiratory Infections ◽  
Protein Structures ◽  
Antiviral Drug ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Mortality And Morbidity ◽  
Evolutionary Forces ◽  
Genome Wide

AbstractHuman influenza A viruses elicit short-term respiratory infections with considerable mortality and morbidity. While H3N2 viruses circulate since almost 50 years, the recent introduction of pH1N1 viruses presents an excellent opportunity for a comparative analysis of the genome-wide evolutionary forces acting on both subtypes. Here, we inferred patches of sites relevant for adaptation, i.e. being under positive selection, on eleven viral protein structures, from all available data since 1968 and correlated these with known functional properties. Overall, pH1N1 had more patches than H3N2 viruses, especially in the viral polymerase complex, while antigenic evolution is more apparent for H3N2 viruses. In both subtypes, NS1 had the highest patch and patch site frequency, indicating that NS1-mediated viral attenuation of host inflammatory responses is a continuously intensifying process, elevated even in the longtime-circulating subtype H3N2. We confirmed the resistance-causing effects of two pH1N1 changes against oseltamivir in NA activity assays, demonstrating the value of the resource for discovering functionally relevant changes. Our results represent an atlas of protein regions and sites with links to host adaptation, antiviral drug resistances and immune evasion for both subtypes for further study.

scholarly journals Structures and functions linked to genome-wide adaptation of human influenza A viruses

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Thorsten R. Klingen ◽  
Jens Loers ◽  
Stephanie Stanelle-Bertram ◽  
Gülsah Gabriel ◽  
Alice C. McHardy
Keyword(s):  
Influenza A ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Genome Wide ◽  
Wide Adaptation

scholarly journals Non-random reassortment in human influenza A viruses

2008 ◽  
Vol 2 (1) ◽  
pp. 9-22 ◽  
Author(s):  
Raul Rabadan ◽  
Arnold J. Levine ◽  
Michael Krasnitz
Keyword(s):  
Influenza A ◽  
Human Influenza ◽  
Influenza A Viruses

scholarly journals N-Glycolylneuraminic Acid in Animal Models for Human Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 815
Author(s):  
Cindy M. Spruit ◽  
Nikoloz Nemanichvili ◽  
Masatoshi Okamatsu ◽  
Hiromu Takematsu ◽  
Geert-Jan Boons ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Animal Models ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Upper Respiratory Tract ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Sialic Acid Content ◽  
Acetylneuraminic Acid

The first step in influenza virus infection is the binding of hemagglutinin to sialic acid-containing glycans present on the cell surface. Over 50 different sialic acid modifications are known, of which N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are the two main species. Animal models with α2,6 linked Neu5Ac in the upper respiratory tract, similar to humans, are preferred to enable and mimic infection with unadapted human influenza A viruses. Animal models that are currently most often used to study human influenza are mice and ferrets. Additionally, guinea pigs, cotton rats, Syrian hamsters, tree shrews, domestic swine, and non-human primates (macaques and marmosets) are discussed. The presence of NeuGc and the distribution of sialic acid linkages in the most commonly used models is summarized and experimentally determined. We also evaluated the role of Neu5Gc in infection using Neu5Gc binding viruses and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH)-/- knockout mice, which lack Neu5Gc and concluded that Neu5Gc is unlikely to be a decoy receptor. This article provides a base for choosing an appropriate animal model. Although mice are one of the most favored models, they are hardly naturally susceptible to infection with human influenza viruses, possibly because they express mainly α2,3 linked sialic acids with both Neu5Ac and Neu5Gc modifications. We suggest using ferrets, which resemble humans closely in the sialic acid content, both in the linkages and the lack of Neu5Gc, lung organization, susceptibility, and disease pathogenesis.

scholarly journals Improving pandemic influenza risk assessment

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Colin A Russell ◽  
Peter M Kasson ◽  
Ruben O Donis ◽  
Steven Riley ◽  
John Dunbar ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Sequence Data ◽  
Virus Genome ◽  
Influenza Viruses ◽  
Influenza Surveillance ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Virus Genotype

Assessing the pandemic risk posed by specific non-human influenza A viruses is an important goal in public health research. As influenza virus genome sequencing becomes cheaper, faster, and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk assessment capabilities. However, the complexities of the relationships between virus genotype and phenotype make such predictions extremely difficult. The integration of experimental work, computational tool development, and analysis of evolutionary pathways, together with refinements to influenza surveillance, has the potential to transform our ability to assess the risks posed to humans by non-human influenza viruses and lead to improved pandemic preparedness and response.

scholarly journals Influenza A and B viruses in the population of Vojvodina, Serbia

2014 ◽  
Vol 66 (1) ◽  
pp. 43-50 ◽  
Author(s):  
J. Radovanov ◽  
V. Milosevic ◽  
I. Hrnjakovic ◽  
V. Petrovic ◽  
M. Ristic ◽  
...  
Keyword(s):  
Influenza A ◽  
Respiratory Infections ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Nasopharyngeal Swab ◽  
Influenza B ◽  
Influenza A Viruses ◽  
B Virus ◽  
Life Threatening ◽  
Seasonal Epidemic

At present, two influenza A viruses, H1N1pdm09 and H3N2, along with influenza B virus co-circulate in the human population, causing endemic and seasonal epidemic acute febrile respiratory infections, sometimes with life-threatening complications. Detection of influenza viruses in nasopharyngeal swab samples was done by real-time RT-PCR. There were 60.2% (53/88) positive samples in 2010/11, 63.4% (52/82) in 2011/12, and 49.9% (184/369) in 2012/13. Among the positive patients, influenza A viruses were predominant during the first two seasons, while influenza B type was more active during 2012/13. Subtyping of influenza A positive samples revealed the presence of A (H1N1)pdm09 in 2010/11, A (H3N2) in 2011/12, while in 2012/13, both subtypes were detected. The highest seroprevalence against influenza A was in the age-group 30-64, and against influenza B in adults aged 30-64 and >65.

scholarly journals Specific therapy and emergency prevention of flu

2021 ◽  
pp. 116-123
Author(s):  
Wassili M. Delyagin
Keyword(s):  
Influenza A ◽  
Respiratory Infections ◽  
Age Groups ◽  
Antiviral Drug ◽  
Risk Groups ◽  
Diagnostic Methods ◽  
High Morbidity ◽  
Low Birth Weight Infants ◽  
Food Treatment ◽  
Number Of Patients

Influenza A and B epidemics, occasionally pandemics, are characterized by high morbidity and mortality rates. In most cases, an uncomplicated disease ends with recovery, but unfavorable outcomes, up to lethal, are possible, especially in premature, low birth weight, infants and young children, old people, pregnant and postpartum women, with chronic diseases, immunocompromised, receiving salicylates and anticoagulants. The use of modern diagnostic methods allows early detection of patients with influenza, distinguishing them from the total number of patients with respiratory infections. This allows you to optimize the timing of the examination, avoid unnecessary prescription of antibiotics, and timely prescribe specific chemotherapy and chemoprophylaxis. During epidemics, in the presence of an epidemiological history, the conclusion of the clinician is decisive for the diagnosis. Vaccination is an excellent method of preventing or relieving the flu. However, in case of an unfavorable course of the disease, in risk groups, in closed groups, it is recommended to use chemotherapy, pre-exposure or post-exposure chemoprophylaxis. Numerous studies have proven the effectiveness of the use of the drug oseltamivir, a specific blocker of the virus neuraminidase. As a result, its replication stops. The drug does not complicate the vaccination, it can be used in vaccinated people, in all age groups, is available in different dosages, and can be used with food. Treatment for uncomplicated influenza lasts 5 days. In certain situations, chemoprophylaxis and chemotherapy with the specific antiviral drug oseltamivir can help control influenza outbreaks in certain populations.

scholarly journals Large-Scale Sequence Analysis of M Gene of Influenza A Viruses from Different Species: Mechanisms for Emergence and Spread of Amantadine Resistance

2009 ◽  
Vol 53 (10) ◽  
pp. 4457-4463 ◽  
Author(s):  
Yuki Furuse ◽  
Akira Suzuki ◽  
Hitoshi Oshitani
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Drug Resistant ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
M Gene ◽  
Drug Pressure ◽  
Human Influenza Virus ◽  
Selective Pressures ◽  
Amantadine Resistance

ABSTRACT Influenza A virus infects many species, and amantadine is used as an antiviral agent. Recently, a substantial increase in amantadine-resistant strains has been reported, most of which have a substitution at amino acid position 31 in the M2 gene. Understanding the mechanism responsible for the emergence and spread of antiviral resistance is important for developing a treatment protocol for seasonal influenza and for deciding on a policy for antiviral stockpiling for pandemic influenza. The present study was conducted to identify the existence of drug pressure on the emergence and spread of amantadine-resistant influenza A viruses. We analyzed data on more than 5,000 virus sequences and constructed a phylogenetic tree to calculate selective pressures on sites in the M2 gene associated with amantadine resistance (positions 26, 27, 30, and 31) among different hosts. The phylogenetic tree revealed that the emergence and spread of the drug-resistant M gene in different hosts and subtypes were independent and not through reassortment. For human influenza virus, positive selection was detected only at position 27. Selective pressures on the sites were not always higher for human influenza virus than for viruses of other hosts. Additionally, selective pressure on position 31 did not increase after the introduction of amantadine. Although there is a possibility of drug pressure on human influenza virus, we could not find positive pressure on position 31. Because the recent rapid increase in drug-resistant virus is associated with the substitution at position 31, the resistance may not be related to drug use.

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