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Viruses
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Lung Immunity to Respiratory Viruses
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Lung Immunity to 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: closed (1 December 2023) | Viewed by 8187

Special Issue Editor

Dr. Wendy Fonseca

E-Mail Website
Guest Editor
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA
Interests: respiratory syncytial virus; asthma; viral immunology

Special Issue Information

Dear Colleagues,

The lung is constantly exposed to viral infection from infancy to the elderly. Some viruses will destroy the epithelium, while others will develop an exacerbated immune response, and some of them will lead to long-term functional changes in the lung. Furthermore, respiratory viral infection also has a great impact on patients with chronic pulmonary diseases.

Respiratory Viruses are usually rapidly recognized and controlled by a coordinated response involving the innate and adaptive immune system. Activating multiple mechanisms is necessary for an efficient antiviral immune response and requires adequate recall responses in the lung that generate protection against secondary challenge infection. This series of primary research and review articles in this Special Issue explores the detailed mechanism by which the lung immune response responds to different respiratory viruses to control replication, lung pathology, clearance to restore lung homeostasis, and recall response to secondary infections.

Dr. Wendy Fonseca
Guest Editor

Manuscript Submission Information

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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

  • lung immunity
  • respiratory virus
  • lung mucosal immunity
  • virus-induced lung immunopathology
  • innate immunity
  • adaptative immunity

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Published Papers (4 papers)

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Research

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14 pages, 2506 KiB  
Article
An Evaluation of Type 1 Interferon Related Genes in Male and Female-Matched, SARS-CoV-2 Infected Individuals Early in the COVID-19 Pandemic
by Tom P. Huecksteadt, Elizabeth J. Myers, Samuel E. Aamodt, Shubhanshi Trivedi and Kristi J. Warren
Viruses 2024, 16(3), 472; https://doi.org/10.3390/v16030472 - 20 Mar 2024
Viewed by 1873
Abstract
SARS-CoV-2 infection has claimed just over 1.1 million lives in the US since 2020. Globally, the SARS-CoV-2 respiratory infection spread to 771 million people and caused mortality in 6.9 million individuals to date. Much of the early literature showed that SARS-CoV-2 immunity was [...] Read more.
SARS-CoV-2 infection has claimed just over 1.1 million lives in the US since 2020. Globally, the SARS-CoV-2 respiratory infection spread to 771 million people and caused mortality in 6.9 million individuals to date. Much of the early literature showed that SARS-CoV-2 immunity was defective in the early stages of the pandemic, leading to heightened and, sometimes, chronic inflammatory responses in the lungs. This lung-associated ‘cytokine storm’ or ‘cytokine release syndrome’ led to the need for oxygen supplementation, respiratory distress syndrome, and mechanical ventilation in a relatively high number of people. In this study, we evaluated circulating PBMC from non-hospitalized, male and female, COVID-19+ individuals over the course of infection, from the day of diagnosis (day 0) to one-week post diagnosis (day 7), and finally 4 weeks after diagnosis (day 28). In our early studies, we included hospitalized and critically care patient PBMC; however, most of these individuals were lymphopenic, which limited our assessments of their immune integrity. We chose a panel of 30 interferon-stimulated genes (ISG) to evaluate by PCR and completed flow analysis for immune populations present in those PBMC. Lastly, we assessed immune activation by stimulating PBMC with common TLR ligands. We identified changes in innate cells, primarily the innate lymphoid cells (ILC, NK cells) and adaptive immune cells (CD4+ and CD8+ T cells) over this time course of infection. We found that the TLR-7 agonist, Resiquimod, and the TLR-4 ligand, LPS, induced significantly better IFNα and IFNγ responses in the later phase (day 28) of SARS-CoV-2 infection in those non-hospitalized COVID-19+ individuals as compared to early infection (day 0 and day 7). We concluded that TLR-7 and TLR-4 agonists may be effective adjuvants in COVID-19 vaccines for mounting immunity that is long-lasting against SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Lung Immunity to Respiratory Viruses)
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12 pages, 1044 KiB  
Article
Interchangeability of the Assays Used to Assess the Activity of Anti-SARS-CoV-2 Monoclonal Antibodies
by Brady T. Hickerson, Alexey M. Khalenkov, Tao Xie, David M. Frucht, Dorothy E. Scott and Natalia A. Ilyushina
Viruses 2023, 15(8), 1698; https://doi.org/10.3390/v15081698 - 5 Aug 2023
Cited by 1 | Viewed by 1385
Abstract
The recent global COVID-19 pandemic caused by SARS-CoV-2 lasted for over three years. A key measure in combatting this pandemic involved the measurement of the monoclonal antibody (mAb)-mediated inhibition of binding between the spike receptor-binding domain (RBD) and hACE2 receptor. Potency assessments of [...] Read more.
The recent global COVID-19 pandemic caused by SARS-CoV-2 lasted for over three years. A key measure in combatting this pandemic involved the measurement of the monoclonal antibody (mAb)-mediated inhibition of binding between the spike receptor-binding domain (RBD) and hACE2 receptor. Potency assessments of therapeutic anti-SARS-CoV-2 mAbs typically include binding or cell-based neutralization assays. We assessed the inhibitory activity of five anti-SARS-CoV-2 mAbs using ELISA, surface plasmon resonance (SPR), and four cell-based neutralization assays using different pseudovirus particles and 293T or A549 cells expressing hACE2 with or without TMPRSS2. We assessed the interchangeability between cell-based and binding assays by applying the Bland–Altman method under certain assumptions. Our data demonstrated that the IC50 [nM] values determined by eight neutralization assays are independent of the cell line, presence of TMPRSS2 enzyme on the cell surface, and pseudovirus backbone used. Moreover, the Bland–Altman analysis showed that the IC50 [nM] and KD [nM] values determined by neutralization/ELISA or by SPR are equivalent and that the anti-spike mAb activity can be attributed to one variable directly related to its tertiary conformational structure conformation, rate dissociation constant Koff. This parameter is independent from the concentrations of the components of the mAb:RBD:hACE2 complexes and can be used for a comparison between the activities of the different mAbs. Full article
(This article belongs to the Special Issue Lung Immunity to Respiratory Viruses)
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19 pages, 1828 KiB  
Article
Immune Prophylaxis Targeting the Respiratory Syncytial Virus (RSV) G Protein
by Harrison C. Bergeron, Jackelyn Murray, Aakash Arora, Ana M. Nuñez Castrejon, Rebecca M. DuBois, Larry J. Anderson, Lawrence M. Kauvar and Ralph A. Tripp
Viruses 2023, 15(5), 1067; https://doi.org/10.3390/v15051067 - 27 Apr 2023
Cited by 3 | Viewed by 2905
Abstract
The respiratory syncytial virus (RSV) causes significant respiratory disease in young infants and the elderly. Immune prophylaxis in infants is currently limited to palivizumab, an anti-RSV fusion (F) protein monoclonal antibody (mAb). While anti-F protein mAbs neutralize RSV, they are unable to prevent [...] Read more.
The respiratory syncytial virus (RSV) causes significant respiratory disease in young infants and the elderly. Immune prophylaxis in infants is currently limited to palivizumab, an anti-RSV fusion (F) protein monoclonal antibody (mAb). While anti-F protein mAbs neutralize RSV, they are unable to prevent aberrant pathogenic responses provoked by the RSV attachment (G) protein. Recently, the co-crystal structures of two high-affinity anti-G protein mAbs that bind the central conserved domain (CCD) at distinct non-overlapping epitopes were solved. mAbs 3D3 and 2D10 are broadly neutralizing and block G protein CX3C-mediated chemotaxis by binding antigenic sites γ1 and γ2, respectively, which is known to reduce RSV disease. Previous studies have established 3D3 as a potential immunoprophylactic and therapeutic; however, there has been no similar evaluation of 2D10 available. Here, we sought to determine the differences in neutralization and immunity to RSV Line19F infection which recapitulates human RSV infection in mouse models making it useful for therapeutic antibody studies. Prophylactic (24 h prior to infection) or therapeutic (72 h post-infection) treatment of mice with 3D3, 2D10, or palivizumab were compared to isotype control antibody treatment. The results show that 2D10 can neutralize RSV Line19F both prophylactically and therapeutically, and can reduce disease-causing immune responses in a prophylactic but not therapeutic context. In contrast, 3D3 was able to significantly (p < 0.05) reduce lung virus titers and IL-13 in a prophylactic and therapeutic regimen suggesting subtle but important differences in immune responses to RSV infection with mAbs that bind distinct epitopes. Full article
(This article belongs to the Special Issue Lung Immunity to Respiratory Viruses)
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Other

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8 pages, 952 KiB  
Brief Report
Comparative Analysis of Pediatric Hospitalizations during Two Consecutive Influenza and Respiratory Virus Seasons Post-Pandemic
by Santiago Presti, Sara Manti, Francesco Gambilonghi, Giuseppe Fabio Parisi, Maria Papale and Salvatore Leonardi
Viruses 2023, 15(9), 1825; https://doi.org/10.3390/v15091825 - 28 Aug 2023
Cited by 9 | Viewed by 1544
Abstract
Background: The COVID-19 pandemic has had a significant impact on the epidemiology of respiratory viruses. Non-pharmaceutical interventions (NPIs) led to a dramatic reduction in respiratory infections. However, the long-term effects on respiratory virus epidemiology remain unclear. Materials and Methods: We conducted a comparative [...] Read more.
Background: The COVID-19 pandemic has had a significant impact on the epidemiology of respiratory viruses. Non-pharmaceutical interventions (NPIs) led to a dramatic reduction in respiratory infections. However, the long-term effects on respiratory virus epidemiology remain unclear. Materials and Methods: We conducted a comparative study on hospitalized pediatric patients with respiratory illness during two seasons: 1 October 2021 to 15 March 2022 and 1 October 2022 to 15 March 2023. We compared the type of virus, mean duration of hospitalization, and disease severity. Results: In the first season, 47.1% of patients (65/138) tested positive for at least one respiratory virus, with respiratory syncytial virus (RSV) being the most frequent (23.2%). In the second season, 82.9% of patients (102/123) tested positive, with RSV and Rhinovirus being the most prevalent (28.38% and 27.03%, respectively). Other viruses, such as Influenza A/B, Metapneumovirus, and Adenovirus, also showed increased prevalence. Disease severity and mean duration of hospitalization were similar between the two seasons. Conclusions: Our study highlights increased prevalence in respiratory viruses, including RSV and Rhinovirus, following the easing of NPIs. The prevalence in respiratory viruses, including RSV and Rhinovirus, increased in the second season compared to the first one. Interestingly, RSV’s peak incidence shifted from February to November. The emergence of rhinovirus as the most prevalent respiratory virus during certain months suggests viral competition and dynamic changes in viral circulation. The overall severity of respiratory infections remained relatively stable between the seasons. Full article
(This article belongs to the Special Issue Lung Immunity to Respiratory Viruses)
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