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Microorganisms
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The Biology of Influenza Viruses
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The Biology of Influenza Viruses

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 36183

Special Issue Editor

Dr. Mariana Baz

E-Mail Website1 Website2
Guest Editor
Research Center in Infectious Diseases of the CHU of Québec and Université Laval, Québec City, QC G1V 4G2, Canada
Interests: influenza viruses; pathogenesis and transmission; antivirals; vaccines; high-risk populations; animal models; clinical studies; emerging and re-emerging viruses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Influenza viruses spread around the world causing annual epidemics and sporadic pandemics which constitute a serious threat to the worldwide health care system and economy. There are four types of influenza viruses: A, B, C, and D. Influenza has high morbidity rates for people of all ages but particularly in high-risk populations such as children, adults >65 years old, patients with chronic illnesses, and pregnant women. In addition to infecting humans, influenza viruses have been isolated from pigs, dogs, cats, seals, and numerous avian species.

In this Special Issue, we aim to gather a collection of research and review articles as well as short communications that provide recent advances in the understanding of the biology of influenza viruses. Topics of interest include but are not limited to human and animal influenza viruses, virus replication, pathogenesis and transmission, mathematical and computational evolutionary biology, preclinical studies, antivirals, and vaccines for immunocompetent and high-risk populations and drug discovery.

Dr. Mariana Baz
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. Microorganisms 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 2700 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

  • Human influenza viruses 
  • Animal influenza viruses 
  • Influenza virus replication 
  • Mathematical and computational evolutionary biology 
  • Novel therapeutic strategies
  • Antivirals
  • Antiviral resistance 
  • Drug discovery 
  • Vaccines 
  • Animal models
  • Phatogenesis and transmission 
  • High-risk populations

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Published Papers (7 papers)

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Research

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13 pages, 958 KiB  
Article
Effects of Different Drug Combinations in Immunodeficient Mice Infected with an Influenza A/H3N2 Virus
by Zeineb Mhamdi, Hugues Fausther-Bovendo, Olus Uyar, Julie Carbonneau, Marie-Christine Venable, Yacine Abed, Gary Kobinger, Guy Boivin and Mariana Baz
Microorganisms 2020, 8(12), 1968; https://doi.org/10.3390/microorganisms8121968 - 11 Dec 2020
Cited by 4 | Viewed by 3029
Abstract
The prolonged treatment of immunosuppressed (IS) individuals with anti-influenza monotherapies may lead to the emergence of drug-resistant variants. Herein, we evaluated oseltamivir and polymerase inhibitors combinations against influenza A/H3N2 infections in an IS mouse model. Mice were IS with cyclophosphamide and infected with [...] Read more.
The prolonged treatment of immunosuppressed (IS) individuals with anti-influenza monotherapies may lead to the emergence of drug-resistant variants. Herein, we evaluated oseltamivir and polymerase inhibitors combinations against influenza A/H3N2 infections in an IS mouse model. Mice were IS with cyclophosphamide and infected with 3 × 103 PFU of a mouse-adapted A/Switzerland/9715293/2013 (H3N2) virus. Forty-eight hours post-infection, the animals started oseltamivir, favipiravir or baloxavir marboxil (BXM) as single or combined therapies for 10 days. Weight losses, survival rates and lung viral titers (LVTs) were determined. The neuraminidase (NA) and polymerase genes from lung viral samples were sequenced. All untreated animals died. Oseltamivir and favipiravir monotherapies only delayed mortality (the mean day to death (MDD) of 21.4 and 24 compared to 11.4 days for those untreated) while a synergistic improvement in survival (80%) and LVT reduction was observed in the oseltamivir/favipiravir group compared to the oseltamivir group. BXM alone or in double/triple combination provided a complete protection and significantly reduced LVTs. Oseltamivir and BXM monotherapies induced the E119V (NA) and I38T (PA) substitutions, respectively, while no resistance mutation was detected with combinations. We found that the multiple dose regimen of BXM alone provided superior benefits compared to oseltamivir and favipiravir monotherapies. Moreover, we suggest the potential for drug combinations to reduce the incidence of resistance. Full article
(This article belongs to the Special Issue The Biology of Influenza Viruses)
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15 pages, 3515 KiB  
Article
Irradiation by a Combination of Different Peak-Wavelength Ultraviolet-Light Emitting Diodes Enhances the Inactivation of Influenza A Viruses
by Mizuki Kojima, Kazuaki Mawatari, Takahiro Emoto, Risa Nishisaka-Nonaka, Thi Kim Ngan Bui, Takaaki Shimohata, Takashi Uebanso, Masatake Akutagawa, Yohsuke Kinouchi, Takahiro Wada, Masayuki Okamoto, Hiroshi Ito, Kenji Tojo, Tomo Daidoji, Takaaki Nakaya and Akira Takahashi
Microorganisms 2020, 8(7), 1014; https://doi.org/10.3390/microorganisms8071014 - 8 Jul 2020
Cited by 15 | Viewed by 5318
Abstract
Influenza A viruses (IAVs) pose a serious global threat to humans and their livestock. This study aimed to determine the ideal irradiation by ultraviolet-light emitting diodes (UV-LEDs) for IAV disinfection. We irradiated the IAV H1N1 subtype with 4.8 mJ/cm2 UV using eight [...] Read more.
Influenza A viruses (IAVs) pose a serious global threat to humans and their livestock. This study aimed to determine the ideal irradiation by ultraviolet-light emitting diodes (UV-LEDs) for IAV disinfection. We irradiated the IAV H1N1 subtype with 4.8 mJ/cm2 UV using eight UV-LEDs [peak wavelengths (WL) = 365, 310, 300, 290, 280, 270, and 260 nm)] or a mercury low pressure (LP)-UV lamp (Peak WL = 254 nm). Inactivation was evaluated by the infection ratio of Madin–Darby canine kidney (MDCK) cells or chicken embryonated eggs. Irradiation by the 260 nm UV-LED showed the highest inactivation among all treatments. Because the irradiation-induced inactivation effects strongly correlated with damage to viral RNA, we calculated the correlation coefficient (RAE) between the irradiant spectrum and absorption of viral RNA. The RAE scores strongly correlated with the inactivation by the UV-LEDs and LP-UV lamp. To increase the RAE score, we combined three different peak WL UV-LEDs (hybrid UV-LED). The hybrid UV-LED (RAE = 86.3) significantly inactivated both H1N1 and H6N2 subtypes to a greater extent than 260 nm (RAE = 68.6) or 270 nm (RAE = 42.2) UV-LEDs. The RAE score is an important factor for increasing the virucidal effects of UV-LED irradiation. Full article
(This article belongs to the Special Issue The Biology of Influenza Viruses)
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22 pages, 2011 KiB  
Article
Epidemiology and Genetic Variability of Circulating Influenza B Viruses in Uruguay, 2012–2019
by María José Rivas, Miguel Alegretti, Leticia Cóppola, Viviana Ramas, Héctor Chiparelli and Natalia Goñi
Microorganisms 2020, 8(4), 591; https://doi.org/10.3390/microorganisms8040591 - 19 Apr 2020
Cited by 11 | Viewed by 3721
Abstract
Influenza B viruses (IBV) are an important cause of morbidity and mortality during interpandemic periods in the human population. Two phylogenetically distinct IBV lineages, B/Yamagata and B/Victoria, co-circulate worldwide and they present challenges for vaccine strain selection. Until the present study, there was [...] Read more.
Influenza B viruses (IBV) are an important cause of morbidity and mortality during interpandemic periods in the human population. Two phylogenetically distinct IBV lineages, B/Yamagata and B/Victoria, co-circulate worldwide and they present challenges for vaccine strain selection. Until the present study, there was little information regarding the pattern of the circulating strains of IBV in Uruguay. A subset of positive influenza B samples from influenza-like illness (ILI) outpatients and severe acute respiratory illness (SARI) inpatients detected in sentinel hospitals in Uruguay during 2012–2019 were selected. The sequencing of the hemagglutinin (HA) and neuraminidase (NA) genes showed substitutions at the amino acid level. Phylogenetic analysis reveals the co-circulation of both lineages in almost all seasonal epidemics in Uruguay, and allows recognizing a lineage-level vaccine mismatch in approximately one-third of the seasons studied. The epidemiological results show that the proportion of IBV found in ILI was significantly higher than the observed in SARI cases across different groups of age (9.7% ILI, 3.2% SARI) and patients between 5–14 years constituted the majority (33%) of all influenza B infection (p < 0.05). Interestingly, we found that individuals >25 years were particularly vulnerable to Yamagata lineage infections. Full article
(This article belongs to the Special Issue The Biology of Influenza Viruses)
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Review

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20 pages, 2974 KiB  
Review
New Technologies for Influenza Vaccines
by Steven Rockman, Karen L. Laurie, Simone Parkes, Adam Wheatley and Ian G. Barr
Microorganisms 2020, 8(11), 1745; https://doi.org/10.3390/microorganisms8111745 - 6 Nov 2020
Cited by 38 | Viewed by 7118
Abstract
Vaccine development has been hampered by the long lead times and the high cost required to reach the market. The 2020 pandemic, caused by a new coronavirus (SARS-CoV-2) that was first reported in late 2019, has seen unprecedented rapid activity to generate a [...] Read more.
Vaccine development has been hampered by the long lead times and the high cost required to reach the market. The 2020 pandemic, caused by a new coronavirus (SARS-CoV-2) that was first reported in late 2019, has seen unprecedented rapid activity to generate a vaccine, which belies the traditional vaccine development cycle. Critically, much of this progress has been leveraged off existing technologies, many of which had their beginnings in influenza vaccine development. This commentary outlines the most promising of the next generation of non-egg-based influenza vaccines including new manufacturing platforms, structure-based antigen design/computational biology, protein-based vaccines including recombinant technologies, nanoparticles, gene- and vector-based technologies, as well as an update on activities around a universal influenza vaccine. Full article
(This article belongs to the Special Issue The Biology of Influenza Viruses)
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13 pages, 1762 KiB  
Review
TRIM Proteins and Their Roles in the Influenza Virus Life Cycle
by Hye-Ra Lee, Myoung Kyu Lee, Chan Woo Kim and Meehyein Kim
Microorganisms 2020, 8(9), 1424; https://doi.org/10.3390/microorganisms8091424 - 16 Sep 2020
Cited by 12 | Viewed by 4535
Abstract
The ubiquitin-proteasome system (UPS) has been recognized for regulating fundamental cellular processes, followed by induction of proteasomal degradation of target proteins, and triggers multiple signaling pathways that are crucial for numerous aspects of cellular physiology. Especially tripartite motif (TRIM) proteins, well-known E3 ubiquitin [...] Read more.
The ubiquitin-proteasome system (UPS) has been recognized for regulating fundamental cellular processes, followed by induction of proteasomal degradation of target proteins, and triggers multiple signaling pathways that are crucial for numerous aspects of cellular physiology. Especially tripartite motif (TRIM) proteins, well-known E3 ubiquitin ligases, emerge as having critical roles in several antiviral signaling pathways against varying viral infections. Here we highlight recent advances in the study of antiviral roles of TRIM proteins toward influenza virus infection in terms of the modulation of pathogen recognition receptor (PRR)-mediated innate immune sensing, direct obstruction of influenza viral propagation, and participation in virus-induced autophagy. Full article
(This article belongs to the Special Issue The Biology of Influenza Viruses)
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17 pages, 956 KiB  
Review
Regulation of Host Immune Responses against Influenza A Virus Infection by Mitogen-Activated Protein Kinases (MAPKs)
by Jiabo Yu, Xiang Sun, Jian Yi Gerald Goie and Yongliang Zhang
Microorganisms 2020, 8(7), 1067; https://doi.org/10.3390/microorganisms8071067 - 17 Jul 2020
Cited by 29 | Viewed by 5364
Abstract
Influenza is a major respiratory viral disease caused by infections from the influenza A virus (IAV) that persists across various seasonal outbreaks globally each year. Host immune response is a key factor determining disease severity of influenza infection, presenting an attractive target for [...] Read more.
Influenza is a major respiratory viral disease caused by infections from the influenza A virus (IAV) that persists across various seasonal outbreaks globally each year. Host immune response is a key factor determining disease severity of influenza infection, presenting an attractive target for the development of novel therapies for treatments. Among the multiple signal transduction pathways regulating the host immune activation and function in response to IAV infections, the mitogen-activated protein kinase (MAPK) pathways are important signalling axes, downstream of various pattern recognition receptors (PRRs), activated by IAVs that regulate various cellular processes in immune cells of both innate and adaptive immunity. Moreover, aberrant MAPK activation underpins overexuberant production of inflammatory mediators, promoting the development of the “cytokine storm”, a characteristic of severe respiratory viral diseases. Therefore, elucidation of the regulatory roles of MAPK in immune responses against IAVs is not only essential for understanding the pathogenesis of severe influenza, but also critical for developing MAPK-dependent therapies for treatment of respiratory viral diseases. In this review, we will summarise the current understanding of MAPK functions in both innate and adaptive immune response against IAVs and discuss their contributions towards the cytokine storm caused by highly pathogenic influenza viruses. Full article
(This article belongs to the Special Issue The Biology of Influenza Viruses)
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13 pages, 3217 KiB  
Review
Evolution and Adaptation of the Avian H7N9 Virus into the Human Host
by Andrew T. Bisset and Gerard F. Hoyne
Microorganisms 2020, 8(5), 778; https://doi.org/10.3390/microorganisms8050778 - 21 May 2020
Cited by 13 | Viewed by 5991
Abstract
Influenza viruses arise from animal reservoirs, and have the potential to cause pandemics. In 2013, low pathogenic novel avian influenza A(H7N9) viruses emerged in China, resulting from the reassortment of avian-origin viruses. Following evolutionary changes, highly pathogenic strains of avian influenza A(H7N9) viruses [...] Read more.
Influenza viruses arise from animal reservoirs, and have the potential to cause pandemics. In 2013, low pathogenic novel avian influenza A(H7N9) viruses emerged in China, resulting from the reassortment of avian-origin viruses. Following evolutionary changes, highly pathogenic strains of avian influenza A(H7N9) viruses emerged in late 2016. Changes in pathogenicity and virulence of H7N9 viruses have been linked to potential mutations in the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA), as well as the viral polymerase basic protein 2 (PB2). Recognizing that effective viral transmission of the influenza A virus (IAV) between humans requires efficient attachment to the upper respiratory tract and replication through the viral polymerase complex, experimental evidence demonstrates the potential H7N9 has for increased binding affinity and replication, following specific amino acid substitutions in HA and PB2. Additionally, the deletion of extended amino acid sequences in the NA stalk length was shown to produce a significant increase in pathogenicity in mice. Research shows that significant changes in transmissibility, pathogenicity and virulence are possible after one or a few amino acid substitutions. This review aims to summarise key findings from that research. To date, all strains of H7N9 viruses remain restricted to avian reservoirs, with no evidence of sustained human-to-human transmission, although mutations in specific viral proteins reveal the efficacy with which these viruses could evolve into a highly virulent and infectious, human-to-human transmitted virus. Full article
(This article belongs to the Special Issue The Biology of Influenza Viruses)
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