Research

17 pages, 4195 KiB

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10040483 - 16 Apr 2021

Cited by 6 | Viewed by 3014

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

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10030316 - 08 Mar 2021

Cited by 1 | Viewed by 1481

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

Open AccessEditor’s ChoiceArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9090725 - 02 Sep 2020

Cited by 7 | Viewed by 3172

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

Jump to: Research, Other

13 pages, 6404 KiB

Open AccessEditor’s ChoiceReview

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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10030355 - 17 Mar 2021

Cited by 26 | Viewed by 4684

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

Open AccessEditor’s ChoiceReview

Anti-Influenza Strategies Based on Nanoparticle Applications

by Klaudia Wieczorek, Barbara Szutkowska and Elzbieta Kierzek

Pathogens 2020, 9(12), 1020; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9121020 - 03 Dec 2020

Cited by 15 | Viewed by 3398

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

Open AccessReview

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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9110951 - 15 Nov 2020

Cited by 7 | Viewed by 3540

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

Open AccessEditor’s ChoiceReview

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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9110925 - 07 Nov 2020

Cited by 16 | Viewed by 3999

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

Open AccessReview

Roles of the Non-Structural Proteins of Influenza A Virus

by Wenzhuo Hao, Lingyan Wang and Shitao Li

Pathogens 2020, 9(10), 812; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9100812 - 03 Oct 2020

Cited by 20 | Viewed by 5703

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

Open AccessCase 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://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10050621 - 18 May 2021

Cited by 22 | Viewed by 3027

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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