Advances in Understanding Viral Pathogenesis and Host Immune Responses to Arboviruses and Respiratory Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 3675

Special Issue Editors


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Guest Editor
1. Laboratory of Infectious Diseases and Molecular Biology, Department of Medicine, Hospital de Niños Dr. Ricardo Gutiérrez, Buenos Aires 1425, Argentina
2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Interests: dengue virus; Zika virus; respiratory syncytial virus; viral immunology; viral pathogenesis; virus–host cell interactions

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Guest Editor
1. Instituto de Química y Fisicoquímica Biológica, Universidad de Buenos Aires, Buenos Aires, Argentina
2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Interests: arboviruses; RNA viruses; chikungunya virus; dengue virus; viral replication; viral genome; virus–host cell interactions
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Special Issue Information

Dear Colleagues,

Arboviruses, including dengue, Zika, chikungunya, and yellow fever viruses, are arthropod-transmitted pathogens that continue to expand their geographic distribution, posing a significant threat to public health worldwide. Despite causing millions of infections each year, effective antiviral treatments and vaccines remain limited for many of them. With global climate change and the increasing spread of arboviruses, there is an urgent need to address the understudied aspects of their pathogenesis to develop effective intervention strategies for future outbreaks.

Respiratory viruses, including influenza virus, rhinovirus, respiratory syncytial virus, parainfluenza virus, metapneumovirus, coronaviruses, and adenoviruses, are the most common causative agents of disease in humans. These viruses are responsible for significant morbidity and mortality, especially in neonates, immunocompromised individuals, and the elderly. Vaccines and antiviral therapy are currently available for only a few of these viruses, which poses a great challenge for continued research on prevention and therapeutic strategies against respiratory viral infections.

With this Special Issue, we aim to explore the pathogenesis of these two important groups of viruses and host immune responses to infections. Understanding viral pathogenesis mechanisms and virus–host immune interactions is crucial for developing safe and effective treatments and vaccines against these viruses with a high impact on global health.

Potential topics of interest for this Special Issue include, but are not limited to, the following:

  • Mechanisms of infection and spread: entry, replication, and dissemination and tissue tropism;
  • Viral evasion strategies: modulation of innate immune responses and mechanisms of persistence;
  • Host factors influencing pathogenesis: genetic and immunological determinants of disease severity and the impact of comorbidities on viral pathogenesis;
  • Innate immunity: role of pattern recognition receptors and interferon and cytokine responses;
  • Adaptive immunity: T cell responses and immune memory formation, B cell responses, and neutralizing antibodies;
  • Cytokine storm and immune dysregulation;
  • Immune modulation and host-directed therapies.

Dr. Laura Beatriz Talarico
Dr. Claudia Filomatori
Guest Editors

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Keywords

  • arboviruses
  • respiratory viruses
  • viral pathogenesis
  • host immune responses
  • innate immunity
  • adaptive immunity
  • viral immune evasion
  • cytokine storm
  • interferon response
  • viral replication
  • viral transmission
  • immunopathology
  • neutralizing antibodies
  • host–virus interactions

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Published Papers (3 papers)

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Research

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17 pages, 3420 KB  
Article
H6N6 Avian Influenza Virus Infection Induced Pyroptosis of M1 Macrophages by Activating Caspase-1
by Hui Zhu, Dongfang He, Sicong Liu, Xiaohui Fan, Lingxi Gao, Liping Guo and Zengfeng Zhang
Viruses 2025, 17(11), 1492; https://doi.org/10.3390/v17111492 - 12 Nov 2025
Viewed by 675
Abstract
The H6N6 avian influenza virus has expanded its host range from birds to mammals. Some strains can now bind to human-like receptors, raising concerns about human infection. Although H6N6 is a low-pathogenic avian influenza virus (LPAIV), it is unclear whether it triggers pyroptosis [...] Read more.
The H6N6 avian influenza virus has expanded its host range from birds to mammals. Some strains can now bind to human-like receptors, raising concerns about human infection. Although H6N6 is a low-pathogenic avian influenza virus (LPAIV), it is unclear whether it triggers pyroptosis in human lungs, a process linked to cytokine storms in infections like H7N9. Here, we found that the chicken-origin H6N6 LPAIV can effectively replicate in and infect human alveolar macrophages and their M1 macrophages. Viral infection of M1 macrophages upregulated the mRNA levels of NLRP3, caspase-1, and Gasdermin D (GSDMD). Subsequently, caspase-1 was activated and cleaved GSDMD protein into its N-terminal fragment (GSDMD-N), which formed pores in the cell membrane and triggered the release of IL-1β and IL-18. Further analysis demonstrated that inhibition of the NLRP3/Caspase-1/GSDMD pathway by specific inhibitors attenuated pyroptosis in infected M1 macrophages. In summary, our study revealed that H6N6 virus infection induces M1 macrophage pyroptosis via the NLRP3/caspase-1/GSDMD pathway. Notably, M1 macrophages inherently produce pro-inflammatory cytokines; their pyroptosis, accompanied by the release of IL-1β and IL-18, can amplify inflammation and potentially trigger a cytokine storm in the lungs. These findings reveal novel pathogenic mechanisms and potential therapeutic targets for avian influenza viruses. Full article
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18 pages, 2033 KB  
Article
Imiquimod, a Promising Broad-Spectrum Antiviral, Prevents SARS-CoV-2 and Canine Coronavirus Multiplication Through the MAPK/ERK Signaling Pathway
by Josefina Vicente, Freddy Armando Peñaranda Figueredo, Stefania Mantovani, Daniela Laura Papademetrio, Sergio Ivan Nemirovsky, Andrea Alejandra Barquero, Carina Shayo and Carlos Alberto Bueno
Viruses 2025, 17(6), 801; https://doi.org/10.3390/v17060801 - 31 May 2025
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Abstract
Respiratory viruses can cause life-threatening conditions such as sepsis and acute respiratory distress syndrome. However, vaccines and effective antivirals are available for only a limited number of infections. The majority of approved antivirals are direct-acting agents, which target viral proteins essential for infection. [...] Read more.
Respiratory viruses can cause life-threatening conditions such as sepsis and acute respiratory distress syndrome. However, vaccines and effective antivirals are available for only a limited number of infections. The majority of approved antivirals are direct-acting agents, which target viral proteins essential for infection. Unfortunately, mutations have already emerged that confer resistance to these antivirals. In addition, there is an urgent need for broad-spectrum antivirals to address the unpredictable emergence of new viruses with pandemic potential. One promising strategy involves modulating the innate immune response and cellular signaling. Imiquimod, a Toll-like receptor 7 (TLR7) agonist, has shown efficacy in murine models of influenza and respiratory syncytial virus (RSV). Additionally, it demonstrates antiviral activity against herpes simplex virus type 1 (HSV-1) and RSV independent of the TLR7/nuclear factor kappa B (NF-κB) pathway, with protein kinase A (PKA) as a crucial downstream effector. In this study, we demonstrate that imiquimod exhibits concentration-dependent antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and canine coronavirus (CCoV) in epithelial cells, underscoring its broad-spectrum action against coronaviruses. Moreover, its anti-coronavirus effect appears to be independent of the TLR/NF-κB and PKA/exchange protein directly activated by cyclic adenosine monophosphate (EPAC) pathways and may instead be linked to the activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. The ability of imiquimod to inhibit coronavirus replication via the MEK/ERK pathway, coupled with its immunomodulatory properties, highlights its potential as a broad-spectrum antiviral. Full article
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Review

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16 pages, 1386 KB  
Review
The Role of Innate Cells During Alphavirus Chikungunya Infection
by Juliane Santos de França da Silva, Livian Maria Silva dos Santos, Célio Valdevino Ferreira Junior, Nathalie de Sena Pereira, Juliana Navarro Ueda Yaochite, Valter Ferreira de Andrade Neto, Paulo Marcos da Matta Guedes, Rafael Freitas De Oliveira França, Ramayana Morais de Medeiros Brito and Manuela Sales Lima Nascimento
Viruses 2025, 17(11), 1469; https://doi.org/10.3390/v17111469 - 1 Nov 2025
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Abstract
Alphavirus chikungunya (CHIKV) is an arthropod-borne alphavirus of the Togaviridae family, transmitted primarily by Aedes aegypti and Ae. albopictus mosquitoes. CHIKV infection often results in debilitating manifestations that compromise quality of life and generate significant socioeconomic impacts. Recurrent epidemics in tropical and subtropical [...] Read more.
Alphavirus chikungunya (CHIKV) is an arthropod-borne alphavirus of the Togaviridae family, transmitted primarily by Aedes aegypti and Ae. albopictus mosquitoes. CHIKV infection often results in debilitating manifestations that compromise quality of life and generate significant socioeconomic impacts. Recurrent epidemics in tropical and subtropical regions underscore the urgent need to better understand the host immune responses and their contribution to disease outcome. CHIKV establishes infection by overcoming the host’s initial immunological barriers. Innate immune cells, including fibroblasts, dendritic cells, macrophages, monocytes, neutrophils and natural killer (NK) cells, are among the first to respond to infection, ensuring a rapid antiviral defense and supporting the development of adaptive immune responses. However, excessive release of inflammatory mediators and prolonged infiltration of innate cells into joint tissues contribute to disease chronicity and the persistence of arthralgia. In this review, we provide a comprehensive synthesis of current evidence on innate cells that serve as targets for CHIKV infection, highlighting mechanisms that promote effective antiviral defense as well as those responsible for pathological inflammation and chronic disease and identifying key gaps that remain to be addressed. Full article
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