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Epidemiology, Pathogenesis and Immunity of Adenovirus

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

Deadline for manuscript submissions: closed (6 March 2026) | Viewed by 8751

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Special Issue Editors

Prof. Dr. Adriana Kajon

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Guest Editor

Lovelace Biomedical Research Institute, Albuquerque, NM 87108, USA
Interests: adenovirus; genetic variability; molecular epidemiology and pathogenesis of human adenovirus acute respiratory infections
Special Issues, Collections and Topics in MDPI journals

Dr. Jay R. Radke

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Guest Editor

1. Idaho Veterans Research and Education Foundation, Boise Veterans Administration Medical Center, Boise, ID 83702, USA
2. Department of Biological Sciences, Boise State University, Boise, ID 83702, USA
Interests: adenoviral gene control of host inflammatory responses to virally infected cells and related modulation of cellular innate immune responses and immunopathogenesis; viral oncogene effects on neoplastically transformed cell susceptibility to antitumor effects of natural killer cells and activated macrophages
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Human adenoviruses (HAdVs) represent a diverse group of pathogens responsible for a wide spectrum of clinical manifestations ranging from mild respiratory tract infections to severe multi-organ disease. Understanding the epidemiology and pathogenesis of adenovirus infections is crucial for developing effective prevention strategies and therapeutic interventions.

This Special Issue aims to explore the multifaceted aspects of adenovirus infections, encompassing studies on viral epidemiology, transmission dynamics, host susceptibility factors, and the underlying mechanisms of viral pathogenesis. Contributions are invited to delve into the molecular virology of adenoviruses, including viral entry, replication strategies, and immune evasion mechanisms. Additionally, epidemiological investigations should shed light on disease trends, outbreak scenarios, and the impact of adenovirus infections on public health.

Prof. Dr. Adriana Kajon
Dr. Jay R. Radke
Guest Editors

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.

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Keywords

human adenovirus
viral infection
pathogenesis
epidemiology
immune response
diagnosis
therapeutics
vaccine development

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Published Papers (7 papers)

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Research

16 pages, 1315 KB

Open AccessArticle

Correlation of Blood Leukocytes, CRP, LDH, and Cytokine Levels with Disease Severity in Children with Adenovirus Pneumonia

by Yuqun Wei, Xia Liu, Guangwan Lian, Ning Han, Yi Chen, Yingying Zhang, Wanli Liang, Xiaotong Zhan, Bing Zhu and Mingqi Zhao

Viruses 2026, 18(3), 364; https://doi.org/10.3390/v18030364 - 16 Mar 2026

Viewed by 328

Abstract

Objective: This study aims to investigate the correlation between blood leukocyte, CRP, LDH, and cytokine levels and the severity of illness in children with adenovirus pneumonia. Methods: A total of 100 children with adenovirus pneumonia (55 mild cases and 45 severe cases) who were treated at Guangzhou Women and Children’s Medical Center from January 2022 to January 2024, and 40 healthy children as a control group, were selected. Clinical data, some laboratory test data, and serum cytokine levels detected by flow cytometry were collected, and statistical methods were used to analyze the correlation between relevant indicators and the severity of the illness. Results: The research showed that among general clinical manifestations, the proportions of children with fever, dyspnea, pleural effusion, and moist rales in the severe group were all higher than those in the mild group (p < 0.05). Among the collected laboratory test data, indicators such as WBC, neutrophils, and LDH were significantly higher than in the mild group and the control group (p < 0.05) and were positively correlated with the severity of the disease. Regarding the tested cytokines, most children with adenovirus pneumonia showed elevated levels, and cytokines such as IL-6, IL-2, and IL-8 were significantly positively correlated with the disease. In the ROC curve analysis, NEU 6.03 × 10⁹/L (sensitivity 82.2%, specificity 72.7%, AUC 0.830) and IL-6 41.823 pg/mL (sensitivity 75.6%, specificity 81.8%, AUC 0.833) demonstrated certain value in the early identification of children with severe disease. Conclusion: In this study, laboratory indicators (C-reactive protein, lactate dehydrogenase, neutrophils, etc.) and changes in the levels of specific cytokines (TNF-β, IL-2, IL-6, IL-8, etc.) in children with adenovirus pneumonia were closely related to the severity of the disease. Notably, neutrophil count and interleukin-6 were significantly positively correlated with disease severity and had high AUC values, suggesting they may be important parameters for early prediction of the progression of mild adenovirus infection to severe disease. Full article

(This article belongs to the Special Issue Epidemiology, Pathogenesis and Immunity of Adenovirus)

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12 pages, 2573 KB

Open AccessArticle

Genomic Epidemiological Characteristics of Enteric Adenovirus F40 and F41 in Yantai, China, from 2022 to 2023

by Peihua Niu, Zhenlu Sun, Yu Zhang, Dapeng Zhang, Yiming Zhao, Yi Zhang, Ping Cheng, Qiao Gao, Yu Li, Lili Zhao, Jie Yan, Hongmei Zheng, Xuejun Ma and Ji Wang

Viruses 2025, 17(12), 1595; https://doi.org/10.3390/v17121595 - 9 Dec 2025

Viewed by 553

Abstract

This study aims to investigate the genomic epidemiological characteristics of enteric adenovirus types F40 and F41 circulating in Yantai from August 2022 to August 2023, with a focus on genetic diversity, recombination events, and their potential implications for public health and vaccine development. A total of 1200 stool specimens were collected from patients with suspected viral diarrhea, and 47 human adenovirus F subgroup positive samples in Yantai were analyzed. HAdV-F subgroup nucleic acid detection and whole-genome sequencing were performed to identify virus types and single nucleotide variants (SNVs). Phylogenetic and recombination analyses were conducted, and viral protein structures were predicted using AlphaFold3. HAdV-F40 strains exhibited relative genetic conservation, with mutations primarily localized to the fiber gene. In contrast, HAdV-F41 strains displayed pronounced genetic divergence, with a higher mutation burden in the hexon gene. Recombination analysis revealed clear intra-typic recombination events within HAdV-F41, particularly in the hexon gene region. Structural modeling indicated that although the overall protein architecture remained intact, amino acid changes in key antigenic regions may influence immune evasion. HAdV-F40 and HAdV-F41 strains circulating in Yantai show marked genetic diversity. Notably, HAdV-F41 undergoes significant recombination events that may enhance viral adaptability and immune escape. These findings provide important molecular evidence to inform future surveillance strategies and vaccine antigen design for HAdV-F subgroups. Full article

(This article belongs to the Special Issue Epidemiology, Pathogenesis and Immunity of Adenovirus)

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23 pages, 17396 KB

Open AccessArticle

Cargo and Biological Properties of Extracellular Vesicles Released from Human Adenovirus Type 4-Infected Lung Epithelial Cells

by Alessio Noghero, Stephanie Byrum, Chioma Okeoma and Adriana E. Kajon

Viruses 2025, 17(10), 1300; https://doi.org/10.3390/v17101300 - 25 Sep 2025

Viewed by 1023

Abstract

Extracellular vesicles (EVs) are rapidly gaining recognition as critical mediators of inter-cellular communication during viral infections. To contribute to fill the gap in knowledge regarding the role of EVs in adenovirus infection, we used human adenovirus type 4 of species Mastadenovirus exoticum (HAdV-E4), a prevalent respiratory and ocular pathogen, and characterized the cargo and biological properties of EVs released by HAdV-E4-infected A549 lung epithelial cells at a pre-lytic stage of infection. Using immunocapture-based isolation and multi-omics approaches, we found that infection profoundly alters the EV uploaded proteome and small non-coding RNA repertoire. Mass spectrometry identified 268 proteins unique to EVs purified from infected cells (AdV-EVs), with enrichment in pathways supporting vesicle trafficking and viral protein translation, and importantly also a few virus-encoded proteins. A small RNA transcriptome analysis showed differential uploading in AdV-EVs of various small non-coding RNAs, including snoRNAs, as well as the presence of virus associated RNAs I and II. Notably, AdV-EVs contained viral genomic DNA and could initiate productive infection upon delivery to naïve cells in the absence of detectable viral particles. Our data suggest that EVs released during the HAdV-E4 infection may serve as vehicles for non-lytic viral dissemination and highlight their possible role in intra-host dissemination Full article

(This article belongs to the Special Issue Epidemiology, Pathogenesis and Immunity of Adenovirus)

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15 pages, 1229 KB

Open AccessArticle

Seroprevalence of Neutralizing Antibodies in Healthy Adults, in Mexico, Against Human and Simian Adenovirus Types

by Raúl E. López, Margarita Valdés Alemán, Jesús M. Torres-Flores, Yordanis Pérez-Llano, David Alejandro Cabrera Gaytán, Clara Esperanza Santacruz Tinoco, Julio Elias Alvarado Yaah, Yu Mei Anguiano Hernández, Bernardo Martínez Miguel, José Esteban Muñoz Medina, Nancy Sandoval Gutiérrez, Ilse Ramos Lagunes, José Antonio Arroyo Pérez and Ramón A. González

Viruses 2025, 17(9), 1184; https://doi.org/10.3390/v17091184 - 29 Aug 2025

Viewed by 1392

Abstract

Replication-defective adenoviruses are widely used as vectors for vaccines, but their efficacy may be compromised by the prevalence of pre-existing neutralizing antibodies from natural infections or prior vaccination with adenovirus-based vaccines. To overcome these limitations, less common human adenovirus (HAdV) types and simian adenoviruses (SAdV) have been explored as alternative vectors to the widely prevalent HAdV-C5. Despite their importance, there is limited information on the epidemiology of adenovirus immunity in many countries and geographical regions, including Mexico. In this study, we analyzed 2488 serum samples from healthy adults across all 32 states of Mexico to assess the prevalence of both total and neutralizing antibodies against various HAdV types from species A-F, and three related SAdVs. Our findings indicate a high prevalence of neutralizing antibodies against HAdV-C5 and HAdV-C6, with significant cross-reactivity observed among related adenoviruses. Notably, HAdV-D26 exhibited a lower prevalence of neutralizing antibodies, suggesting its potential suitability as a vector for vaccine development in populations with high pre-existing immunity to more common HAdV types. These results provide critical insights for optimizing adenovirus-based vaccine strategies in Mexico. Full article

(This article belongs to the Special Issue Epidemiology, Pathogenesis and Immunity of Adenovirus)

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21 pages, 4768 KB

Open AccessArticle

Differential Expression of Host miRNAs During Ad14 and Ad14p1 Infection

by Eric R. McIndoo, Ethan Wood, Gina Kuffel, Michael J. Zilliox and Jay R. Radke

Viruses 2025, 17(6), 838; https://doi.org/10.3390/v17060838 - 11 Jun 2025

Viewed by 983

Abstract

Adenovirus is a frequent cause of mild, usually self-limited infections in infants and young children. Severe infections occur in immunocompromised patients but are rarely observed in healthy, immunocompetent adults. However, there have been outbreaks of infections with different adenoviral (Ad) types around the world that have resulted in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in some of those infected. Ad14p1 is the predominant circulating strain of Ad14 worldwide that has caused ARDS. An explanation for the severity of illness caused by Ad14p1 infection in immunocompetent patients is unknown. Previously, we have shown that A549 cells infected with Ad14 repress macrophage pro-inflammatory responses, whereas cells infected with Ad14p1 fail to repress macrophages and instead can increase pro-inflammatory responses. Adenoviral infection has been shown to modulate host miRNA expression, and we hypothesized that differences in miRNA expression between Ad14- and Ad14p1-infected cells might explain the differential responses of macrophages to Ad14- and Ad14p1-infected cells. Analysis of host miRNA showed that 98 miRNAs are differentially expressed when infection reaches full cytopathic effect (CPE), the same point at which Ad14 and Ad14p1 CPE corpses induce differential inflammatory responses in macrophages. Only 10 of the miRNAs that were enriched in Ad14 CPE corpses were expressed at levels that are potentially biologically relevant. Pathway enrichment analysis showed that the differentially expressed miRNAs might explain the increased pathogenesis of Ad14p1 through strain-related loss of modulation of cytokine expression when compared with prototype Ad14. Overall, the data suggest a role for viral regulation of host miRNA expression in pathogenesis by regulating host inflammatory responses through the delivery of de-regulated miRNAs by viral CPE corpses to macrophages. Full article

(This article belongs to the Special Issue Epidemiology, Pathogenesis and Immunity of Adenovirus)

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16 pages, 878 KB

Open AccessArticle

Wastewater-Based Surveillance of Human Adenoviruses in Italy: Quantification by Digital PCR and Molecular Typing via Nanopore Amplicon Sequencing

by Carolina Veneri, G. Bonanno Ferraro, D. Congiu, A. Franco, D. Brandtner, P. Mancini, M. Iaconelli, The SARI Network, L. Lucentini, E. Suffredini and Giuseppina La Rosa

Viruses 2025, 17(6), 791; https://doi.org/10.3390/v17060791 - 30 May 2025

Cited by 2 | Viewed by 1799

Abstract

Wastewater-based epidemiology (WBE) offers valuable insight into viral circulation at the community level. In this study, we combined digital PCR (dPCR) with molecular typing to investigate the prevalence and diversity of human adenoviruses (HAdVs) in untreated wastewater samples collected throughout Italy. HAdV genomes were detected in over 93% of the 168 samples analyzed, with concentrations up to 4.5 × 10⁶ genome copies per liter. For genotypic characterization, we used nested PCR followed by Sanger and Oxford Nanopore Technologies (ONTs) long-read sequencing. While Sanger sequencing identified three dominant genotypes (HAdV-A12, HAdV-B3, and HAdV-F41), ONT sequencing provided enhanced resolution, confirming all previously identified types and revealing seven additional genotypes: HAdV-B21, HAdV-C5, HAdV-D45, HAdV-D46, HAdV-D49, HAdV-D83, and HAdV-F40. This comprehensive approach highlights the added value of ONT long-read sequencing in uncovering the genetic complexity of adenoviruses in wastewater, particularly in detecting rare or low abundance types that conventional methods may miss. Our findings highlight the value of integrating quantitative and high-resolution molecular tools in WBE to improve surveillance and better understand the epidemiology of viral pathogens circulating in the human population. Full article

(This article belongs to the Special Issue Epidemiology, Pathogenesis and Immunity of Adenovirus)

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12 pages, 858 KB

Open AccessArticle

Modulation of the Inflammatory Response by Adenovirus 36 in Patients with Obesity and Type 2 Diabetes: A Nested Case-Control Study Within a Cohort

by Itzae Adonai Gutiérrez-Hurtado, Erika Martínez-López, Manuel Alejandro Rico-Méndez, Karla Mayela Bravo-Villagra, Héctor Eduardo Mendoza-Jaramillo, María del Pilar Sánchez-Rolón, Alejandra Betancourt-Núñez, Martha Patricia Gallegos-Arreola, José Carlos Tapia-Rivera and Andres López-Quintero

Viruses 2025, 17(4), 552; https://doi.org/10.3390/v17040552 - 10 Apr 2025

Viewed by 1337

Abstract

Human adenovirus 36 (HAdV-36) is associated with obesity, potentially by promoting adipocyte proliferation and differentiation. Although linked to increased fat storage, HAdV-36 is also correlated with improved insulin sensitivity. Given its potential role in modulating adipose tissue and promoting a less inflammatory metabolic profile, its impacts on pro- and anti-inflammatory cytokine secretion remain unclear. Methods: This nested case-control study compared cytokine levels (IL-10, IL-2, IL-6, IL-8, and TNF-α) between patients with and without HAdV-36 infection. A total of 76 participants were included, with 37 in the control group (HAdV-36 negative) and 39 classified as cases (HAdV-36 positive). Results: HAdV-36 seropositive individuals exhibited significantly lower IL-6 levels and higher IL-8 levels than seronegative participants. Additionally, they had lower glucose levels, suggesting a potential link between HAdV-36 and metabolic regulation. Conclusions: These findings support the hypothesis that HAdV-36 may influence inflammatory and metabolic responses by modulating cytokine expression and glucose levels. Further research is needed to clarify the underlying mechanisms and their implications for metabolic health. Full article

(This article belongs to the Special Issue Epidemiology, Pathogenesis and Immunity of Adenovirus)

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