- Exploration of genes and identification of evolutionary evidence in adeno-associated viruses
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Chanhee Lee, Jihong Min, Somin Lim, Anyeseu Park, Seokjin Kwak, Soyeon Hwang, Sooyeon Park, Yong-Suk Jang, Se-Yeoun Cha, Sung-Gook Cho, Jeong Yoon Lee
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J. Microbiol. 2026;64(2):e2511016. Published online February 28, 2026
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DOI: https://doi.org/10.71150/jm.2511016
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 Abstract
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Adeno-associated virus (AAV) commonly infects humans and non-human primates, generally inducing mild or even asymptomatic outcomes. AAVs have been shaped and diversified by evolutionary pressures, resulting in the identification of 13 serotypes thus far. Each serotype of AAV exhibits distinct tissue tropisms, targeting various organs, including the lung, central nervous system (CNS), liver, and skeletal muscle, thereby establishing AAVs as widely utilized vectors for therapeutic gene delivery. Bioinformatics analysis of specific viruses enables the inference of evolutionary patterns and offers valuable insights for predicting the emergence of novel viruses. While DNA sequence-based analysis has effectively facilitated the observation of mutation patterns accumulating within specific genes, it often provides limited insight into the actual impact of these mutations on proteins, the fundamental functional units. Utilizing proteotyping, an amino acid sequence-based comparative analysis, we identified hypervariable regions (HVR) within the AAV Cap gene and revealed concentrated evolutionary pressures in serotypes 4, 5, 11, and 12. Furthermore, we found that AAV-5 proteins exhibited considerable amino acid sequence divergence compared to those of other serotypes. Despite divergence, all AAV-5 proteins maintained a noticeable structural similarity to their counterparts in other serotypes. Our findings provide sequence-based insights into the evolutionary processes of AAV, facilitating the efficient identification of novel viruses.
- Genomic Evolution and Recombination Dynamics of Human Adenovirus D Species: Insights from Comprehensive Bioinformatic Analysis
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Anyeseu Park, Chanhee Lee, Jeong Yoon Lee
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J. Microbiol. 2024;62(5):393-407. Published online March 7, 2024
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DOI: https://doi.org/10.1007/s12275-024-00112-5
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Human adenoviruses (HAdVs) can infect various epithelial mucosal cells, ultimately causing different symptoms in infected organ systems. With more than 110 types classified into seven species (A-G), HAdV-D species possess the highest number of viruses and are the fastest proliferating. The emergence of new adenovirus types and increased diversity are driven by homologous recombination (HR) between viral genes, primarily in structural elements such as the penton base, hexon and fiber proteins, and the E1 and E3 regions. A comprehensive analysis of the HAdV genome provides valuable insights into the evolution of human adenoviruses and identifies genes that display high variation across the entire genome to determine recombination patterns. Hypervariable regions within genetic sequences correlate with functional characteristics, thus allowing for adaptation to new environments and hosts. Proteotyping of newly emerging and already established adenoviruses allows for prediction of the characteristics of novel viruses. HAdV-D species evolved in a direction that increased diversity through gene recombination. Bioinformatics analysis across the genome, particularly in highly variable regions, allows for the verification or re-evaluation of recombination patterns in both newly introduced and pre-existing viruses, ultimately aiding in tracing various biological traits such as virus tropism and pathogenesis. Our research does not only assist in predicting the emergence of new adenoviruses but also offers critical guidance in regard to identifying potential regulatory factors of homologous recombination hotspots.
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Citations
Citations to this article as recorded by  - Adenovirus Genotypes Associated With Severe Acute Respiratory Infections Outbreak in Children, in Antioquia, Colombia, 2022–2023
María Angélica Maya, Celeny Ortiz, Francisco Averhoff, Ana Isabel Davila, Diego Bastidas, Michael G. Berg, Gavin A. Cloherty, Laura S. Perez-Restrepo, Karl Ciuoderis-Aponte, Jaime Usuga, Isabel Moreno, Juan P. Hernandez-Ortiz, Paulina A. Rebolledo, Jorge
Pediatric Infectious Disease Journal.2026; 45(2): 112. CrossRef - Exploration of genes and identification of evolutionary evidence in adeno-associated viruses
Chanhee Lee, Jihong Min, Somin Lim, Anyeseu Park, Seokjin Kwak, Soyeon Hwang, Sooyeon Park, Yong-Suk Jang, Se-Yeoun Cha, Sung-Gook Cho, Jeong Yoon Lee
Journal of Microbiology.2026; 64(2): e2511016. CrossRef - A novel chimpanzee-derived adenovirus, a recombinant of Mastadenovirus exoticum and Mastadenovirus blackbeardi members, reveals lineage-specific recombination hotspots in simian adenoviruses
Ereth A. Robles-Chávez, Raúl E. López, Ramón A. González, Angélica Valle-Constantino, León P. Martínez Castilla, Adan Barbosa-López, Selene Maldonado-López, Julio C. Medina Ávila, Ma Isabel Salazar, Arturo Reyes-Sandoval, Jesús M. Torres-Flores
Virology.2026; 618: 110855. CrossRef - Deciphering 6-mer Spectra Distribution Rules in Coronavirus Genomes: Application to Comparative Genomic Analysis
Zhenhua Yang, Hong Li, Xiaolong Li, Guojun Liu
International Journal of Molecular Sciences.2026; 27(8): 3604. CrossRef - Relationship between adenovirus infection and intussusception via pathological evidence confirms
Lung-Huang Lin, Chi-Jung Huang, Cheng-Yu Lo, Yu-Hsien Lee, Yung-Chuan Chen
Journal of Clinical Pathology.2025; 78(10): 678. CrossRef - Diagnostic Performance of a Silver-Amplified vs. a Non-Amplified Lateral Flow Kit for Adenoviral Conjunctivitis: A Multicenter Prospective Study
Tsuguto Fujimoto, Nozomu Hanaoka, Kenichiro Takahashi, Hisatoshi Kaneko, Masaaki Kobayashi, Hisashi Nakagawa, Hiroshi Hatano, Tomoko Tsukahara-Kawamura, Hironori Migita, Kentaro Nakamura, Kiyoharu Kuramoto, Eiichi Uchio
Viruses.2025; 17(11): 1442. CrossRef - In Silico Intensive Analysis for the E4 Gene Evolution of Human Adenovirus Species D
Chanhee Lee, Anyeseu Park, Jeong Yoon Lee
Journal of Microbiology.2024; 62(5): 409. CrossRef
- In Silico Intensive Analysis for the E4 Gene Evolution of Human Adenovirus Species D
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Chanhee Lee, Anyeseu Park, Jeong Yoon Lee
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J. Microbiol. 2024;62(5):409-418. Published online April 30, 2024
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DOI: https://doi.org/10.1007/s12275-024-00132-1
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374
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6
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3
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3
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Abstract
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Adenovirus (Ad) is a ubiquitous pathogen capable of infecting a wide range of animals and humans. Human Adenovirus (HAdV) can cause severe infection, particularly in individuals with compromised immune systems. To date, over 110 types of HAdV have been classified into seven species from A to G, with the majority belonging to the human adenovirus species D (HAdV-D). In the HAdV-D, the most significant factor for the creation of new adenovirus types is homologous recombination between viral genes involved in determining the virus tropism or evading immune system of host cells. The E4 gene, consisting of seven Open Reading Frames (ORFs), plays a role in both the regulation of host cell metabolism and the replication of viral genes. Despite long-term studies, the function of each ORF remains unclear. Based on our updated information, ORF2, ORF3, and ORF4 have been identified as regions with relatively high mutations compared to other ORFs in the E4 gene, through the use of in silico comparative analysis. Additionally, we managed to visualize high mutation sections, previously undetectable at the DNA level, through a powerful amino acid sequence analysis tool known as proteotyping. Our research has revealed the involvement of the E4 gene in the evolution of human adenovirus, and has established accurate sequence information of the E4 gene, laying the groundwork for further research.
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Citations
Citations to this article as recorded by - A novel chimpanzee-derived adenovirus, a recombinant of Mastadenovirus exoticum and Mastadenovirus blackbeardi members, reveals lineage-specific recombination hotspots in simian adenoviruses
Ereth A. Robles-Chávez, Raúl E. López, Ramón A. González, Angélica Valle-Constantino, León P. Martínez Castilla, Adan Barbosa-López, Selene Maldonado-López, Julio C. Medina Ávila, Ma Isabel Salazar, Arturo Reyes-Sandoval, Jesús M. Torres-Flores
Virology.2026; 618: 110855. CrossRef - Commentary: E4orf1 as a key modulator in oncogenesis and of metabolism in Adenovirus infection
Masoud Nateqi, Vijay Hegde, Nikhil V. Dhurandhar
Frontiers in Virology.2026;[Epub] CrossRef - Exploration of genes and identification of evolutionary evidence in adeno-associated viruses
Chanhee Lee, Jihong Min, Somin Lim, Anyeseu Park, Seokjin Kwak, Soyeon Hwang, Sooyeon Park, Yong-Suk Jang, Se-Yeoun Cha, Sung-Gook Cho, Jeong Yoon Lee
Journal of Microbiology.2026; 64(2): e2511016. CrossRef
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