RSV and HMPV Infections in 3D Tissue Cultures: Mechanisms Involved in Virus-Host and Virus-Virus Interactions

Respiratory viral infections constitute a global public health concern. Among prevalent respiratory viruses, two pneumoviruses can be life-threatening in high-risk populations. In young children, they constitute the first cause of hospitalization due to severe lower respiratory tract diseases. A better understanding of their pathogenesis is still needed as there are no approved efficient anti-viral nor vaccine against pneumoviruses. We studied Respiratory Syncytial virus (RSV) and human Metapneumovirus (HMPV) in single and dual infections in three-dimensional cultures, a highly relevant model to study viral respiratory infections of the airway epithelium. Our investigation showed that HMPV is less pathogenic than RSV in this model. Compared to RSV, HMPV replicated less efficiently, induced a lower immune response, did not block cilia beating, and was more sensitive to IFNs. In dual infections, RSV-infected epithelia were less permissive to HMPV. By neutralizing IFNs in co-infection assays, we partially prevented HMPV inhibition by RSV and significantly increased the number of co-infected cells in the tissue. This suggests that interference in dual infection would be at least partly mediated by the host immune response. In summary, this work provides new insight regarding virus-host and virus-virus interactions of pneumoviruses in the airway epithelium. This could be helpful for the proper handling of at-risk patients.

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A differential regulatory T cell signature distinguishes the immune landscape of COVID-19 hospitalized patients from those hospitalized with other respiratory viral infections

10.1101/2021.03.25.21254376 ◽

2021 ◽

Author(s):

Sarah C Vick ◽

Marie Frutoso ◽

Florian Mair ◽

Andrew J Konecny ◽

Evan Greene ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Regulatory T Cell ◽

Viral Infections ◽

Respiratory Infections ◽

Expression Patterns ◽

Depth Profiling ◽

Treatment Strategies ◽

Host Responses ◽

Syncytial Virus

SARS-CoV-2 infection has caused a lasting global pandemic costing millions of lives and untold additional costs. Understanding the immune response to SARS-CoV-2 has been one of the main challenges in the past year in order to decipher mechanisms of host responses and interpret disease pathogenesis. Comparatively little is known in regard to how the immune response against SARS-CoV-2 differs from other respiratory infections. In our study, we compare the peripheral blood immune signature from SARS-CoV-2 infected patients to patients hospitalized pre-pandemic with Influenza Virus or Respiratory Syncytial Virus (RSV). Our in-depth profiling indicates that the immune landscape in patients infected by SARS-CoV-2 is largely similar to patients hospitalized with Flu or RSV. Similarly, serum cytokine and chemokine expression patterns were largely overlapping. Unique to patients infected with SARS-CoV-2 who had the most critical clinical disease state were changes in the regulatory T cell (Treg) compartment. A Treg signature including increased frequency, activation status, and migration markers was correlated with the severity of COVID-19 disease. These findings are particularly relevant as Tregs are being discussed as a therapy to combat the severe inflammation seen in COVID-19 patients. Likewise, having defined the overlapping immune landscapes in SARS-CoV-2, existing knowledge of Flu and RSV infections could be leveraged to identify common treatment strategies.

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Differential Mucin Expression by Respiratory Syncytial Virus and Human Metapneumovirus Infection in Human Epithelial Cells

Mediators of Inflammation ◽

10.1155/2015/347292 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Ma. Del Rocío Baños-Lara ◽

Boyang Piao ◽

Antonieta Guerrero-Plata

Keyword(s):

Immune Response ◽

Respiratory Syncytial Virus ◽

Epithelial Cells ◽

Viral Infections ◽

Human Metapneumovirus ◽

Human Epithelial Cells ◽

Mucin Expression ◽

Rsv Infection ◽

Syncytial Virus ◽

Tract Disease

Mucins (MUC) constitute an important component of the inflammatory and innate immune response. However, the expression of these molecules by respiratory viral infections is still largely unknown. Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two close-related paramyxoviruses that can cause severe low respiratory tract disease in infants and young children worldwide. Currently, there is not vaccine available for neither virus. In this work, we explored the differential expression of MUC by RSV and hMPV in human epithelial cells. Our data indicate that the MUC expression by RSV and hMPV differs significantly, as we observed a stronger induction of MUC8, MUC15, MUC20, MUC21, and MUC22 by RSV infection while the expression of MUC1, MUC2, and MUC5B was dominated by the infection with hMPV. These results may contribute to the different immune response induced by these two respiratory viruses.

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Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

Pathogens ◽

10.3390/pathogens11010047 ◽

2021 ◽

Vol 11 (1) ◽

pp. 47

Author(s):

Catalina A. Andrade ◽

Alexis M. Kalergis ◽

Karen Bohmwald

Keyword(s):

Respiratory Syncytial Virus ◽

Viral Infections ◽

Respiratory Infections ◽

The Elderly ◽

Cell Types ◽

Potential Effect ◽

Viral Agent ◽

Pulmonary Manifestations ◽

Syncytial Virus ◽

Tract Infections

Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.

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Contribution of Resident Memory CD8+ T Cells to Protective Immunity Against Respiratory Syncytial Virus and Their Impact on Vaccine Design

Pathogens ◽

10.3390/pathogens8030147 ◽

2019 ◽

Vol 8 (3) ◽

pp. 147 ◽

Cited By ~ 9

Author(s):

Retamal-Díaz ◽

Covián ◽

Pacheco ◽

Castiglione-Matamala ◽

Bueno ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Respiratory Syncytial Virus ◽

Viral Infections ◽

Memory T Cells ◽

Effector Memory ◽

Memory Cells ◽

Effective Immune Response ◽

Syncytial Virus ◽

Tract Infections

Worldwide, human respiratory syncytial virus (RSV) is the most common etiological agent for acute lower respiratory tract infections (ALRI). RSV-ALRI is the major cause of hospital admissions in young children, and it can cause in-hospital deaths in children younger than six months old. Therefore, RSV remains one of the pathogens deemed most important for the generation of a vaccine. On the other hand, the effectiveness of a vaccine depends on the development of immunological memory against the pathogenic agent of interest. This memory is achieved by long-lived memory T cells, based on the establishment of an effective immune response to viral infections when subsequent exposures to the pathogen take place. Memory T cells can be classified into three subsets according to their expression of lymphoid homing receptors: central memory cells (TCM), effector memory cells (TEM) and resident memory T cells (TRM). The latter subset consists of cells that are permanently found in non-lymphoid tissues and are capable of recognizing antigens and mounting an effective immune response at those sites. TRM cells activate both innate and adaptive immune responses, thus establishing a robust and rapid response characterized by the production of large amounts of effector molecules. TRM cells can also recognize antigenically unrelated pathogens and trigger an innate-like alarm with the recruitment of other immune cells. It is noteworthy that this rapid and effective immune response induced by TRM cells make these cells an interesting aim in the design of vaccination strategies in order to establish TRM cell populations to prevent respiratory infectious diseases. Here, we discuss the biogenesis of TRM cells, their contribution to the resolution of respiratory viral infections and the induction of TRM cells, which should be considered for the rational design of new vaccines against RSV.

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Parainfluenza type 3 outbreaks in Izmir children, Turkey

Tropical Doctor ◽

10.1258/004947507782333170 ◽

2007 ◽

Vol 37 (4) ◽

pp. 252-254

Author(s):

Figen Gülen ◽

Candan Cicek ◽

Zafer Kurugol ◽

Esen Demir ◽

Dost Zeyrek ◽

...

Keyword(s):

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Viral Infections ◽

Respiratory Infections ◽

Lower Respiratory Tract Infections ◽

Parainfluenza Viruses ◽

Syncytial Virus ◽

Aetiological Diagnosis ◽

Tract Infections ◽

Type 3

The present study was aimed to investigate characteristics of lower respiratory tract infections caused by parainfluenza type 3 viruses. Nasopharyngeal smears were taken from 178 patients with lower respiratory infections for the diagnosis of respiratory syncytial virus, adenovirus, influenza and parainfluenza viruses between December 2004 and April 2005. Parainfluenza type 3 was isolated from the viral specimens of 96 (53.9%) patients and it was noticeable that the parainfluenza type 3 outbreak occurs during winter. Obviously, improving the aetiological diagnosis of viral infections might avoid unnecessary therapy, antibiotics in particular, and would allow for preventive isolation of infected patients.

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Comparison of rates of hospitalization between single and dual virus detection in a Mexican cohort of children and adults with influenza-like illness

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz424 ◽

2019 ◽

Author(s):

Daniel E Noyola ◽

Sally Hunsberger ◽

Raydel Valdés Salgado ◽

John H Powers ◽

Arturo Galindo-Fraga ◽

...

Keyword(s):

Viral Infections ◽

Respiratory Infections ◽

Simultaneous Detection ◽

Virus Detection ◽

Clinical Information ◽

Detection Methods ◽

Acute Respiratory Infections ◽

Virus Infections ◽

Influenza Like Illness ◽

Syncytial Virus

Abstract Background Molecular detection methods allow for the simultaneous detection of several infectious agents. This study assesses whether co-infection with two viruses as compared to one is associated with increased hospitalization in those with acute respiratory infections. Methods We prospectively enrolled a cohort of pediatric and adult participants with influenza-like illness during 2010-2014 in Mexico. Clinical information and respiratory samples were collected at enrollment. Respiratory viruses were detected with multiplex PCR and influenza specific RT-PCR assays. Participants were followed-up 14 and 28 days after inclusion. Severity of disease as measured by hospitalization with acute respiratory infections was compared between single and dual viral infections. Results Among 5,662 participants in the study, either one (n=3,285) or two (n=641) viruses were detected in 3,926 participants. Rhinovirus (n=1,433), influenza (n=888), and coronaviruses (n=703) were the most frequently detected viruses (either alone or in co-infection). Bocavirus, respiratory syncytial virus (RSV), metapneumovirus, and rhinovirus cases were hospitalized more often than other viruses. Bocavirus+rhinovirus cases were hospitalized more often than those with rhinovirus alone (but not bocavirus alone). RSV cases were more likely to be hospitalized than cases with co-infections of RSV and parainfluenza virus or coronavirus. Metapneumovirus cases were hospitalized more often than those co-infected with metapneumovirus+coronavirus. Conclusions In this study, detection of two viruses did not significantly increase hospitalizations compared with single virus infections. Larger studies will allow for distinguishing between sequential and simultaneous infection as well as for a better understanding of the role of each virus during the evolution of acute respiratory episodes.

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Immunological, Viral, Environmental, and Individual Factors Modulating Lung Immune Response to Respiratory Syncytial Virus

BioMed Research International ◽

10.1155/2015/875723 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Silvia Vandini ◽

Paolo Bottau ◽

Giacomo Faldella ◽

Marcello Lanari

Keyword(s):

Immune Response ◽

Respiratory Syncytial Virus ◽

Animal Models ◽

Respiratory Tract Infections ◽

Clinical Course ◽

Respiratory Infections ◽

Syncytial Virus ◽

High Risk Infants ◽

Tract Infections ◽

Lung Response

Respiratory syncytial virus is a worldwide pathogen agent responsible for frequent respiratory tract infections that may become severe and potentially lethal in high risk infants and adults. Several studies have been performed to investigate the immune response that determines the clinical course of the infection. In the present paper, we review the literature on viral, environmental, and host factors influencing virus response; the mechanisms of the immune response; and the action of nonimmunological factors. These mechanisms have often been studied in animal models and in the present review we also summarize the main findings obtained from animal models as well as the limits of each of these models. Understanding the lung response involved in the pathogenesis of these respiratory infections could be useful in improving the preventive strategies against respiratory syncytial virus.

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Acute respiratory infections and flu during the COVID-19 pandemic. What to expect in 2021–2022?

Russian Medical Inquiry ◽

10.32364/2587-6821-2021-5-11-721-727 ◽

2021 ◽

Vol 5 (11) ◽

pp. 721-727

Author(s):

D.V. Usenko ◽

◽

N.Kh. Tkhakushinova ◽

T.T. Shaturina ◽

L.A. Ledenko ◽

...

Keyword(s):

Viral Infection ◽

Sodium Alginate ◽

Viral Infections ◽

Respiratory Infections ◽

Antiviral Agent ◽

Risk Groups ◽

Control Measures ◽

Acute Respiratory Infections ◽

Respiratory Viral Infection ◽

Syncytial Virus

This paper discusses the spread of the most common causative agents for respiratory viral infections, i.e., respiratory syncytial virus (RSV) and influenza virus (IV), during seasonal peaks and under the COVID-19 pandemic. The COVID-19 pandemic and epidemic control measures reduced the transmission of some respiratory viral pathogens. The authors specify the risks of changes in RSV epidemiology associated with restrictions and their lifting. Possible scenarios of virus "behavior" in 2021–2022 are represented. These scenarios include the return of variants registered at the end of 2019 and the risk of the emergence of a novel strain of zoonotic flu that may result in a novel viral pandemic. It was demonstrated that effective monitoring of causative agent circulation, timely specific prophylaxis (particularly in high-risk groups), and early effective antiviral therapy are crucial irrespective of the possible scenario of respiratory viral infection. Modern principles of complex flu and acute respiratory viral infection treatment using an antiviral agent based on rimantadine and sodium alginate are addressed. KEYWORDS: flu, COVID-19, pandemic, respiratory syncytial infection, children, treatment, rimantadine, sodium alginate. FOR CITATION: Usenko D.V., Tkhakushinova N.Kh., Shaturina T.T. et al. Acute respiratory infections and flu during the COVID-19 pandemic. What to expect in 2021–2022? Russian Medical Inquiry. 2021;5(11):721–727 (in Russ.). DOI: 10.32364/2587-6821-2021- 5-11-721-727.

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Depletion of TAX1BP1 amplifies innate immune responses during respiratory syncytial virus infection

Journal of Virology ◽

10.1128/jvi.00912-21 ◽

2021 ◽

Author(s):

Delphyne Descamps ◽

Andressa Peres de Oliveira ◽

Lorène Gonnin ◽

Sarah Madrières ◽

Jenna Fix ◽

...

Keyword(s):

Immune Response ◽

Respiratory Syncytial Virus ◽

Respiratory Infections ◽

The Elderly ◽

Cellular Protein ◽

Innate Immune ◽

Efficient Treatment ◽

Rsv Infection ◽

Syncytial Virus ◽

Nucleoprotein N

Respiratory syncytial virus (RSV) is the main cause of acute respiratory infections in young children, and also has a major impact on the elderly and immunocompromised people. In the absence of a vaccine or efficient treatment, a better understanding of RSV interactions with the host antiviral response during infection is needed. Previous studies revealed that cytoplasmic inclusion bodies (IBs) where viral replication and transcription occur could play a major role in the control of innate immunity during infection by recruiting cellular proteins involved in the host antiviral response. We recently showed that the morphogenesis of IBs relies on a liquid-liquid phase separation mechanism depending on the interaction between viral nucleoprotein (N) and phosphoprotein (P). These scaffold proteins are expected to play a central role in the recruitment of cellular proteins to IBs. Here, we performed a yeast two-hybrid screen using RSV N protein as a bait, and identified the cellular protein TAX1BP1 as a potential partner of this viral protein. This interaction was validated by pulldown and immunoprecipitation assays. We showed that TAX1BP1 suppression has only a limited impact on RSV infection in cell cultures. However, RSV replication is decreased in TAX1BP1-deficient mice (TAX1BP1 KO ), whereas the production of inflammatory and antiviral cytokines is enhanced. In vitro infection of wild-type or TAX1BP1 KO alveolar macrophages confirmed that the innate immune response to RSV infection is enhanced in the absence of TAX1BP1. Altogether, our results suggest that RSV could hijack TAX1BP1 to restrain the host immune response during infection. Importance Respiratory syncytial virus (RSV), which is the leading cause of lower respiratory tract illness in infants, still remains a medical problem in the absence of vaccine or efficient treatment. This virus is also recognized as a main pathogen in the elderly and immunocompromised people, and the occurrence of co-infections (with other respiratory viruses and bacteria) amplifies the risks of developing respiratory distress. In this context, a better understanding of the pathogenesis associated to viral respiratory infections, which depends on both viral replication and the host immune response, is needed. The present study reveals that the cellular protein TAX1BP1, which interacts with the RSV nucleoprotein N, participates in the control of the innate immune response during RSV infection, suggesting that N-TAX1BP1 interaction represents a new target for the development of antivirals.

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Type III interferons disrupt the lung epithelial barrier upon viral recognition

10.1101/2020.05.05.077867 ◽

2020 ◽

Cited By ~ 4

Author(s):

Achille Broggi ◽

Sreya Ghosh ◽

Benedetta Sposito ◽

Roberto Spreafico ◽

Fabio Balzarini ◽

...

Keyword(s):

Immune Response ◽

Viral Infections ◽

Rna Virus ◽

Virus Infections ◽

Highly Pathogenic ◽

Type Iii ◽

Lung Epithelial ◽

Syncytial Virus ◽

Tract Infections ◽

Viral Recognition

AbstractLower respiratory tract infections are a leading cause of mortality driven by infectious agents. RNA viruses such as influenza virus, respiratory syncytial virus and the new pandemic coronavirus SARS-CoV-2 can be highly pathogenic. Clinical and experimental evidence indicate that most severe and lethal cases do not depend on the viral burden and are, instead, characterized by an aberrant immune response. In this work we assessed how the innate immune response contributes to the pathogenesis of RNA virus infections. We demonstrate that type III interferons produced by dendritic cells in the lung in response to viral recognition cause barrier damage and compromise the host tissue tolerance. In particular, type III interferons inhibit tissue repair and lung epithelial cell proliferation, causing susceptibility to lethal bacterial superinfections. Overall, our data give a strong mandate to rethink the pathophysiological roles of this group of interferons and their possible use in the clinical practice against endemic as well as emerging viral infections.

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