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Viruses
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Antigenic Drift in Respiratory Viruses
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Antigenic Drift in Respiratory Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 1705

Special Issue Editor

Dr. Gabriel Gonzalez

E-Mail Website
Guest Editor
1. Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan
2. National Virus Reference Laboratory, University College Dublin, Belfield, Dublin, Ireland
Interests: respiratory viruses; pathogens; vaccines; viral evolution; risk assessment; virus characterization; zoonotic viruses

Special Issue Information

Dear Colleagues,

Understanding the evolutionary patterns that increase the diversity of viral respiratory pathogens has become paramount. The recent COVID-19 pandemic experience highlighted how a virus can spread in the population and negatively affect all human activities in multiple countries with socioeconomic consequences lasting for years. Furthermore, the world faces increasing risks of major infectious outbreaks posed by other pathogens, such as influenza virus, adenovirus, respiratory syncytial virus, and even other members of the Coronaviridae family. In this context, technological and analytical approaches have made it possible to simulate in silico, and experimentally characterize in detail, the effects of viral diversity. Such characterizations extend also to predictions regarding diverse variants of viruses, better identification of evolutionary events such as host-switching and recombination/reassortment, and methods to surveil viral agents affecting public health. This Special Issue aims to compile scientific reports on these efforts to disseminate best practices aimed to aid in the development of accessible diagnostics and treatments, and the prevention of future infectious outbreaks. As proper shared knowledge is the key to preventing and ameliorating the consequences of the next pandemic, this is an invitation to join this endeavor by showcasing the results of your work and their potential applications.

Dr. Gabriel Gonzalez
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 250 words) can be sent to the Editorial Office for assessment.

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. Viruses 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 2600 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

  • respiratory viruses
  • virus diversity
  • viral recombination
  • reassortment
  • zoonotic viruses
  • wastewater pathogen surveillance
  • viral sequencing
  • virus evolutionary characterization
  • animal viruses

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Published Papers (3 papers)

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Research

19 pages, 14856 KB  
Article
Genomic Evolution of Influenza A(H1N1)pdm09 and A/H3N2 Viruses Among Children in Wuhan, China, Spanning the COVID-19 Pandemic (2020–2023)
by Muhammad Arif Rizwan, Ying Li, Jiaming Huang, Haizhou Liu, Muhammad Noman, Ismaila Damilare Isiaka, Hebin Chen, Wenqing Li, Yuehu Liu, Huaying Wang, Yuyi Xiao, Yi Yan, Xiaoxia Lu and Di Liu
Viruses 2026, 18(2), 210; https://doi.org/10.3390/v18020210 - 5 Feb 2026
Abstract
Despite the persistent global threat of seasonal influenza viruses such as A(H1N1)pdm09 and A/H3N2, their epidemiological and genetic characteristics in China following the implementation of COVID-19 non-pharmaceutical interventions (NPIs) remain poorly characterized. Between September 2020 and December 2023, we conducted an integrated epidemiological [...] Read more.
Despite the persistent global threat of seasonal influenza viruses such as A(H1N1)pdm09 and A/H3N2, their epidemiological and genetic characteristics in China following the implementation of COVID-19 non-pharmaceutical interventions (NPIs) remain poorly characterized. Between September 2020 and December 2023, we conducted an integrated epidemiological and genomic analysis of influenza A viruses in children in Wuhan. The overall positivity rate for influenza A virus was markedly low at 3.43% (109/3171), reflecting a profound suppression of circulation during the pandemic. Among genotyped positives, H1N1pdm09 was predominant (52.3%), followed by H3N2 (16.5%) and untypeable strains (32.1%). Preschool children showed the highest susceptibility. Phylogenetic analysis revealed that the circulating H1N1 strains (90%) belonged to clade 6B.1A.5a.2, clustering with viruses from Hong Kong and Pakistan. In contrast, H3N2 strains (76.92%) primarily fell into clade 3C.2a1b.2a.2b, closely related to contemporary strains from Europe and North America. Notably, we identified key hemagglutinin mutations associated with antigenic drift (e.g., R240Q in H1N1; E78G, R158G in H3N2) and neuraminidase mutations potentially conferring antiviral resistance (e.g., S247N in H1N1; S245N, a putative novel glycosylation site, in H3N2). Evidence of reassortment events was also detected, underscoring the continued genomic evolution of these viruses despite their low prevalence. Our findings demonstrate that genetically diverse and antigenically drifted influenza A viruses continued to circulate and evolve in Wuhan during the COVID-19 pandemic, albeit at dramatically reduced levels. This highlights the critical need for sustained genomic surveillance and timely updates of vaccine compositions to pre-empt the resurgence of influenza in the post-pandemic era. Full article
(This article belongs to the Special Issue Antigenic Drift in Respiratory Viruses)
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15 pages, 2726 KB  
Article
Tiled-Amplicon Whole-Genome Sequencing Method Reveals Endemic Circulation of Human Adenovirus Type 3 in Japan
by Gabriel Gonzalez, Naganori Nao, Koshiro Tabata, Yukari Itakura, Shinji Saito, Kenichiro Takahashi, Masaaki Kobayashi, Nobuyoshi Kitaichi, Nobuhisa Ishiguro, Tsuguto Fujimoto, Adriana E. Kajon, Hirofumi Sawa and Nozomu Hanaoka
Viruses 2026, 18(1), 74; https://doi.org/10.3390/v18010074 - 5 Jan 2026
Viewed by 365
Abstract
Human adenovirus type 3 (HAdV-3) in the species Mastadenovirus blackbeardi is a frequent cause of hundreds of respiratory infections in Japan, with outbreaks varying in clinical severity. Such a high frequency of cases could be due to regular migration of novel variants or [...] Read more.
Human adenovirus type 3 (HAdV-3) in the species Mastadenovirus blackbeardi is a frequent cause of hundreds of respiratory infections in Japan, with outbreaks varying in clinical severity. Such a high frequency of cases could be due to regular migration of novel variants or persistent circulation of endemic strains. Either scenario would require different measures to ameliorate the burden on public health. We designed a new cost-effective whole-genome sequencing protocol based on tiled amplicons and nanopore sequencing to clarify the circumstances behind the frequent outbreaks. This protocol was used with clinical samples collected between 2011 and 2020 from Japanese patients with acute respiratory illness (n = 110), resulting in near whole-genome sequences (~99% length) for 105 samples with high read coverage (~262.6 ± 192 reads). Phylogenetic analysis indicated sustained circulation of endemic strains in Japan during the analyzed decade and their relation to other strains worldwide with publicly available genome sequences. However, a comparison with other Japanese HAdV-3 strains circulating since 2023 suggested the public health measures introduced during the COVID-19 pandemic (2020–2022) indirectly affected the prevalence of circulating HAdV-3 variants. Additionally, our approach enabled the detection and partial sequencing (~71% completion) of co-infecting strains from the species Mastadenovirus caesari (n = 4) in the examined samples. The detection of adenoviruses belonging to different species in the same sample highlights how our protocol enhances the distinction of circulating viruses. In conclusion, these results and the introduced protocol will enable timely characterization and clinical interventions to mitigate this virus. Full article
(This article belongs to the Special Issue Antigenic Drift in Respiratory Viruses)
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12 pages, 3199 KB  
Article
H128N Substitution in the Sa Antigenic Site of HA1 Causes Antigenic Drift Between Eurasian Avian-like H1N1 and 2009 Pandemic H1N1 Influenza Viruses
by Fei Meng, Zhang Cheng, Zijian Feng, Yijie Zhang, Yali Zhang, Yanwen Wang, Yujia Zhai, Peichun Kuang, Rui Qu, Yan Chen, Chuanling Qiao, Hualan Chen and Huanliang Yang
Viruses 2025, 17(10), 1360; https://doi.org/10.3390/v17101360 - 12 Oct 2025
Viewed by 1010
Abstract
The antigenic relationship between Eurasian avian-like H1N1 swine influenza viruses (EA H1N1) and human pandemic 2009 H1N1 viruses (2009/H1N1) remains a critical question for influenza surveillance and vaccine efficacy. This study systematically investigated the antigenic differences between strains A/swine/Tianjin/312/2016 (TJ312, EA H1N1) and [...] Read more.
The antigenic relationship between Eurasian avian-like H1N1 swine influenza viruses (EA H1N1) and human pandemic 2009 H1N1 viruses (2009/H1N1) remains a critical question for influenza surveillance and vaccine efficacy. This study systematically investigated the antigenic differences between strains A/swine/Tianjin/312/2016 (TJ312, EA H1N1) and A/Guangdong-Maonan/SWL1536/2019 (GD1536, 2009/H1N1). Cross-hemagglutination inhibition (HI) assays revealed a significant antigenic disparity, with a 16-fold reduction in heterologous versus homologous HI titers. Comparative sequence analysis identified 22 amino acid differences across the five major antigenic sites (Sa, Sb, Ca1, Ca2, and Cb) of the HA1 subunit. Using reverse genetics, a panel of mutant viruses was generated. This study revealed that a single histidine (H)-to-asparagine (N) substitution at residue 128 (H3 numbering) in the Sa antigenic site acts as a primary determinant of antigenic variation, sufficient to cause a four-fold change in HI titers and a measurable drift in antigenic distance. Structural modeling via AlphaFold3 and PyMOL software suggests that the H128N mutation may alter the local conformation of the antigenic site. It is plausible that H at position 128 could exert electrostatic repulsion with adjacent amino acids, whereas N might facilitate hydrogen bond formation with neighboring residues. These interactions would potentially lead to structural changes in the antigenic site. Our findings confirm that residue 128 is a critical molecular marker for the antigenic differentiation of EA H1N1 and 2009/H1N1 viruses. The study underscores the necessity of monitoring specific HA mutations that could reduce cross-reactivity and provides valuable insights for refining vaccine strain selection and pandemic preparedness strategies. Full article
(This article belongs to the Special Issue Antigenic Drift in Respiratory Viruses)
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