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Pathogens
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Advance in Influenza A Virus
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Advance in Influenza A Virus

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 40900

Special Issue Editor

Dr. Pawel Zmora

E-Mail Website
Guest Editor
Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznań, Poland
Interests: influenza virus; virus-host interaction; antivirals; hemagglutinin; RNA structure
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The influenza A virus (IVA) has been present for centuries, with remedies such as the influenza vaccine and specific anti-influenza treatment (i.e., amantadine, oseltamivir) having been around for nearly a century or for several years, respectively. Nevertheless, IAV continues to cause illness every 6 seconds and a death every 2 minutes today. To combat influenza, we need to understand virus biology at the cellular and organism level and combine this knowledge with human immunology, physiology and genetic, as well as epidemiological data, basic knowledge on the chemistry of antivirals, as well as development and formulation of vaccines.

However, due to the amazing IAV evolution rate, the emergence of new IAV strains, as well as IAV adaptation to new hosts and environments, we need to reanalyze and confirm our findings. Even though, through many years on the IAV research, we have found solutions to many problems, many questions still remain unanswered, and even more questions not even asked.

In this Special Issue of Pathogens, we invite you to submit research articles, reviews or short communications focused on the recent advances in IAV biology, including cell entry, replication, virus budding and release, IAV genetics and structure, as well as virus–host interaction, development of new antivirals and vaccines, and finally, IAV diagnostics and epidemiology.

Dr. Pawel Zmora
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • influenza A virus
  • viral life cycle
  • virus-host interaction
  • antivirals
  • vaccine
  • epidemiology

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Published Papers (9 papers)

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Research

Jump to: Review, Other

17 pages, 4195 KiB  
Article
Rapid and Efficient Cell-to-Cell Transmission of Avian Influenza H5N1 Virus in MDCK Cells Is Achieved by Trogocytosis
by Supasek Kongsomros, Suwimon Manopwisedjaroen, Jarinya Chaopreecha, Sheng-Fan Wang, Suparerk Borwornpinyo and Arunee Thitithanyanont
Pathogens 2021, 10(4), 483; https://doi.org/10.3390/pathogens10040483 - 16 Apr 2021
Cited by 8 | Viewed by 3776
Abstract
Viruses have developed direct cell-to-cell transfer strategies to enter target cells without being released to escape host immune responses and antiviral treatments. These strategies are more rapid and efficient than transmission through indirect mechanisms of viral infection between cells. Here, we demonstrate that [...] Read more.
Viruses have developed direct cell-to-cell transfer strategies to enter target cells without being released to escape host immune responses and antiviral treatments. These strategies are more rapid and efficient than transmission through indirect mechanisms of viral infection between cells. Here, we demonstrate that an H5N1 influenza virus can spread via direct cell-to-cell transfer in Madin-Darby canine kidney (MDCK) cells. We compared cell-to-cell transmission of the H5N1 virus to that of a human influenza H1N1 virus. The H5N1 virus has been found to spread to recipient cells faster than the human influenza H1N1 virus. Additionally, we showed that plasma membrane exchange (trogocytosis) occurs between co-cultured infected donor cells and uninfected recipient cells early point, allowing the intercellular transfer of viral material to recipient cells. Notably, the H5N1 virus induced higher trogocytosis levels than the H1N1 virus, which could explain the faster cell-to-cell transmission rate of H5N1. Importantly, this phenomenon was also observed in A549 human lung epithelial cells, which are representative cells in the natural infection site. Altogether, our results provide evidence demonstrating that trogocytosis could be the additional mechanism utilized by the H5N1 virus for rapid and efficient cell-to-cell transmission. Full article
(This article belongs to the Special Issue Advance in Influenza A Virus)
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18 pages, 3650 KiB  
Article
Spread of Influenza Viruses in Poland and Neighboring Countries in Seasonal Terms
by Karol Szymański, Ewelina Hallmann, Katarzyna Łuniewska, Katarzyna Kondratiuk, Anna Poznańska and Lidia B. Brydak
Pathogens 2021, 10(3), 316; https://doi.org/10.3390/pathogens10030316 - 8 Mar 2021
Cited by 3 | Viewed by 1976
Abstract
In Poland, flu supervision is coordinated by the National Influenza Center at the National Institute of Public Health—National Institute of Hygiene. In this publication, we want to determine geographical trends in influenza virus circulation in the region. A detailed analysis of virological and [...] Read more.
In Poland, flu supervision is coordinated by the National Influenza Center at the National Institute of Public Health—National Institute of Hygiene. In this publication, we want to determine geographical trends in influenza virus circulation in the region. A detailed analysis of virological and epidemiological data showed the course of the epidemic season in Poland, as well as in neighboring countries. The spatial differentiation of the incidence of infection between voivodships was examined, as well as compared to countries that border a given voivodship. The results show a significant variation in the incidence of infection in terms of time and space. This points to the need to increase the number of tests and to raise awareness among health care professionals and the public about the probability of an influenza pandemic, as undetected viruses can spread further into the European Union. Full article
(This article belongs to the Special Issue Advance in Influenza A Virus)
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13 pages, 3545 KiB  
Article
In Vitro Characterization of Multidrug-Resistant Influenza A(H1N1)pdm09 Viruses Carrying a Dual Neuraminidase Mutation Isolated from Immunocompromised Patients
by Emi Takashita, Seiichiro Fujisaki, Masaru Yokoyama, Masayuki Shirakura, Hiroko Morita, Kazuya Nakamura, Noriko Kishida, Tomoko Kuwahara, Hironori Sato, Ikuko Doi, Yuji Sato, Shinichi Takao, Yukie Shimazu, Takeshi Shimomura, Takuo Ito, Shinji Watanabe, Takato Odagiri and on behalf of The Influenza Virus Surveillance Group of Japan
Pathogens 2020, 9(9), 725; https://doi.org/10.3390/pathogens9090725 - 2 Sep 2020
Cited by 10 | Viewed by 3805
Abstract
Influenza A(H1N1)pdm09 viruses carrying a dual neuraminidase (NA) substitution were isolated from immunocompromised patients after administration of one or more NA inhibitors. These mutant viruses possessed an H275Y/I223R, H275Y/I223K, or H275Y/G147R substitution in their NA and showed enhanced cross-resistance to oseltamivir and peramivir [...] Read more.
Influenza A(H1N1)pdm09 viruses carrying a dual neuraminidase (NA) substitution were isolated from immunocompromised patients after administration of one or more NA inhibitors. These mutant viruses possessed an H275Y/I223R, H275Y/I223K, or H275Y/G147R substitution in their NA and showed enhanced cross-resistance to oseltamivir and peramivir and reduced susceptibility to zanamivir compared to single H275Y mutant viruses. Baloxavir could be a treatment option against the multidrug-resistant viruses because these dual H275Y mutant viruses showed susceptibility to this drug. The G147R substitution appears to stabilize the NA structure, with the fitness of the H275Y/G147R mutant virus being similar or somewhat better than that of the wild-type virus. Since the multidrug-resistant viruses may be able to transmit between humans, surveillance of these viruses must continue to improve clinical management and to protect public health. Full article
(This article belongs to the Special Issue Advance in Influenza A Virus)
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Review

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13 pages, 6404 KiB  
Review
Squalene-Based Influenza Vaccine Adjuvants and Their Impact on the Hemagglutinin-Specific B Cell Response
by Phuong Nguyen-Contant, Mark Y. Sangster and David J. Topham
Pathogens 2021, 10(3), 355; https://doi.org/10.3390/pathogens10030355 - 17 Mar 2021
Cited by 33 | Viewed by 5875
Abstract
Influenza infections continue to cause significant annual morbidity and mortality despite ongoing influenza vaccine research. Adjuvants are administered in conjunction with influenza vaccines to enhance the immune response and strengthen protection against disease. Squalene-based emulsion adjuvants including MF59, AS03, and AF03, are registered [...] Read more.
Influenza infections continue to cause significant annual morbidity and mortality despite ongoing influenza vaccine research. Adjuvants are administered in conjunction with influenza vaccines to enhance the immune response and strengthen protection against disease. Squalene-based emulsion adjuvants including MF59, AS03, and AF03, are registered for administration with influenza vaccines and are widely used in many countries. Squalene-based emulsion adjuvants induce a strong innate immune response, enhancing antigen presentation both quantitively and qualitatively to generate strong B cell responses and antibody production. They also diversify the reactivity profiles and strengthen the affinities of antibodies against the influenza hemagglutinin, increasing protection across virus clades. In this review, we consider the mechanisms of the enhancement of innate and adaptive immune responses by squalene-based emulsionSE adjuvants and the resulting increase in magnitude and breadth of hemagglutinin-specific B cell responses. We relate observed effects of SE adjuvants and current mechanistic understandings to events in responding lymph nodes. These insights will guide the rational design and optimization of influenza vaccines to provide broad and effective protection. Full article
(This article belongs to the Special Issue Advance in Influenza A Virus)
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24 pages, 1580 KiB  
Review
Anti-Influenza Strategies Based on Nanoparticle Applications
by Klaudia Wieczorek, Barbara Szutkowska and Elzbieta Kierzek
Pathogens 2020, 9(12), 1020; https://doi.org/10.3390/pathogens9121020 - 3 Dec 2020
Cited by 16 | Viewed by 4163
Abstract
Influenza virus has the potential for being one of the deadliest viruses, as we know from the pandemic’s history. The influenza virus, with a constantly mutating genome, is becoming resistant to existing antiviral drugs and vaccines. For that reason, there is an urgent [...] Read more.
Influenza virus has the potential for being one of the deadliest viruses, as we know from the pandemic’s history. The influenza virus, with a constantly mutating genome, is becoming resistant to existing antiviral drugs and vaccines. For that reason, there is an urgent need for developing new therapeutics and therapies. Despite the fact that a new generation of universal vaccines or anti-influenza drugs are being developed, the perfect remedy has still not been found. In this review, various strategies for using nanoparticles (NPs) to defeat influenza virus infections are presented. Several categories of NP applications are highlighted: NPs as immuno-inducing vaccines, NPs used in gene silencing approaches, bare NPs influencing influenza virus life cycle and the use of NPs for drug delivery. This rapidly growing field of anti-influenza methods based on nanotechnology is very promising. Although profound research must be conducted to fully understand and control the potential side effects of the new generation of antivirals, the presented and discussed studies show that nanotechnology methods can effectively induce the immune responses or inhibit influenza virus activity both in vitro and in vivo. Moreover, with its variety of modification possibilities, nanotechnology has great potential for applications and may be helpful not only in anti-influenza but also in the general antiviral approaches. Full article
(This article belongs to the Special Issue Advance in Influenza A Virus)
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19 pages, 1015 KiB  
Review
Organization of the Influenza A Virus Genomic RNA in the Viral Replication Cycle—Structure, Interactions, and Implications for the Emergence of New Strains
by Julita Piasecka, Aleksandra Jarmolowicz and Elzbieta Kierzek
Pathogens 2020, 9(11), 951; https://doi.org/10.3390/pathogens9110951 - 15 Nov 2020
Cited by 8 | Viewed by 4234
Abstract
The influenza A virus is a human pathogen causing respiratory infections. The ability of this virus to trigger seasonal epidemics and sporadic pandemics is a result of its high genetic variability, leading to the ineffectiveness of vaccinations and current therapies. The source of [...] Read more.
The influenza A virus is a human pathogen causing respiratory infections. The ability of this virus to trigger seasonal epidemics and sporadic pandemics is a result of its high genetic variability, leading to the ineffectiveness of vaccinations and current therapies. The source of this variability is the accumulation of mutations in viral genes and reassortment enabled by its segmented genome. The latter process can induce major changes and the production of new strains with pandemic potential. However, not all genetic combinations are tolerated and lead to the assembly of complete infectious virions. Reports have shown that viral RNA segments co-segregate in particular circumstances. This tendency is a consequence of the complex and selective genome packaging process, which takes place in the final stages of the viral replication cycle. It has been shown that genome packaging is governed by RNA–RNA interactions. Intersegment contacts create a network, characterized by the presence of common and strain-specific interaction sites. Recent studies have revealed certain RNA regions, and conserved secondary structure motifs within them, which may play functional roles in virion assembly. Growing knowledge on RNA structure and interactions facilitates our understanding of the appearance of new genome variants, and may allow for the prediction of potential reassortment outcomes and the emergence of new strains in the future. Full article
(This article belongs to the Special Issue Advance in Influenza A Virus)
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19 pages, 959 KiB  
Review
RNA Secondary Structure as a First Step for Rational Design of the Oligonucleotides towards Inhibition of Influenza A Virus Replication
by Marta Szabat, Dagny Lorent, Tomasz Czapik, Maria Tomaszewska, Elzbieta Kierzek and Ryszard Kierzek
Pathogens 2020, 9(11), 925; https://doi.org/10.3390/pathogens9110925 - 7 Nov 2020
Cited by 19 | Viewed by 4771
Abstract
Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness [...] Read more.
Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness of vaccination and anti-influenza drugs. Hence, there is a necessity to develop new antiviral drugs and strategies to limit the influenza spread. IAV is a single-stranded negative sense RNA virus with a genome (viral RNA—vRNA) consisting of eight segments. Segments within influenza virion are assembled into viral ribonucleoprotein (vRNP) complexes that are independent transcription-replication units. Each step in the influenza life cycle is regulated by the RNA and is dependent on its interplay and dynamics. Therefore, viral RNA can be a proper target to design novel therapeutics. Here, we briefly described examples of anti-influenza strategies based on the antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA) and catalytic nucleic acids. In particular we focused on the vRNA structure-function relationship as well as presented the advantages of using secondary structure information in predicting therapeutic targets and the potential future of this field. Full article
(This article belongs to the Special Issue Advance in Influenza A Virus)
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19 pages, 1679 KiB  
Review
Roles of the Non-Structural Proteins of Influenza A Virus
by Wenzhuo Hao, Lingyan Wang and Shitao Li
Pathogens 2020, 9(10), 812; https://doi.org/10.3390/pathogens9100812 - 3 Oct 2020
Cited by 26 | Viewed by 7329
Abstract
Influenza A virus (IAV) is a segmented, negative single-stranded RNA virus that causes seasonal epidemics and has a potential for pandemics. Several viral proteins are not packed in the IAV viral particle and only expressed in the infected host cells. These proteins are [...] Read more.
Influenza A virus (IAV) is a segmented, negative single-stranded RNA virus that causes seasonal epidemics and has a potential for pandemics. Several viral proteins are not packed in the IAV viral particle and only expressed in the infected host cells. These proteins are named non-structural proteins (NSPs), including NS1, PB1-F2 and PA-X. They play a versatile role in the viral life cycle by modulating viral replication and transcription. More importantly, they also play a critical role in the evasion of the surveillance of host defense and viral pathogenicity by inducing apoptosis, perturbing innate immunity, and exacerbating inflammation. Here, we review the recent advances of these NSPs and how the new findings deepen our understanding of IAV–host interactions and viral pathogenesis. Full article
(This article belongs to the Special Issue Advance in Influenza A Virus)
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Other

Jump to: Research, Review

12 pages, 587 KiB  
Case Report
Serological Evidence of Backyard Pig Exposure to Highly Pathogenic Avian Influenza H5N8 Virus during 2016–2017 Epizootic in France
by Séverine Hervé, Audrey Schmitz, François-Xavier Briand, Stéphane Gorin, Stéphane Quéguiner, Éric Niqueux, Frédéric Paboeuf, Axelle Scoizec, Sophie Le Bouquin-Leneveu, Nicolas Eterradossi and Gaëlle Simon
Pathogens 2021, 10(5), 621; https://doi.org/10.3390/pathogens10050621 - 18 May 2021
Cited by 26 | Viewed by 3747
Abstract
In autumn/winter 2016–2017, HPAI-H5N8 viruses belonging to the A/goose/Guandong/1/1996 (Gs/Gd) lineage, clade 2.3.4.4b, were responsible for outbreaks in domestic poultry in Europe, and veterinarians were requested to reinforce surveillance of pigs bred in HPAI-H5Nx confirmed mixed herds. In this context, ten pig herds [...] Read more.
In autumn/winter 2016–2017, HPAI-H5N8 viruses belonging to the A/goose/Guandong/1/1996 (Gs/Gd) lineage, clade 2.3.4.4b, were responsible for outbreaks in domestic poultry in Europe, and veterinarians were requested to reinforce surveillance of pigs bred in HPAI-H5Nx confirmed mixed herds. In this context, ten pig herds were visited in southwestern France from December 2016 to May 2017 and serological analyses for influenza A virus (IAV) infections were carried out by ELISA and hemagglutination inhibition assays. In one herd, one backyard pig was shown to have produced antibodies directed against a virus bearing a H5 from clade 2.3.4.4b, suggesting it would have been infected naturally after close contact with HPAI-H5N8 contaminated domestic ducks. Whereas pigs and other mammals, including humans, may have limited sensitivity to HPAI-H5 clade 2.3.4.4b, this information recalls the importance of implementing appropriate biosecurity measures in pig and poultry farms to avoid IAV interspecies transmission, a prerequisite for co-infections and subsequent emergence of new viral genotypes whose impact on both animal and human health cannot be predicted. Full article
(This article belongs to the Special Issue Advance in Influenza A Virus)
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