scholarly journals Type III interferons disrupt the lung epithelial barrier upon viral recognition

2020 ◽  
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.

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

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 147 ◽  
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.

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

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
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.

Clinical use of Antiviral Drugs

1987 ◽  
Vol 21 (5) ◽  
pp. 399-405 ◽  
Author(s):  
Milap C. Nahata
Keyword(s):  
Influenza A ◽  
Viral Infections ◽  
Antiviral Agent ◽  
Antiviral Drugs ◽  
Investigational Drug ◽  
Virus Infections ◽  
Herpes Encephalitis ◽  
Herpes Simplex Viruses ◽  
Varicella Zoster ◽  
Syncytial Virus

Remarkable progress has been made in antiviral chemotherapy. Six approved antiviral drugs are now available for the treatment of various viral infections. Trifluridine, idoxuridine and vidarabine are all effective in patients with herpes keratitis; trifluridine is preferred due to its low toxicity. Acyclovir is the drug of choice in patients with infections due to herpes simplex viruses, including genital herpes, herpes encephalitis, and neonatal herpes, and infections due to varicella-zoster virus. Amantadine is the only drug currently available for prophylaxis and treatment of influenza A, but an investigational drug, rimantadine, appears to be equally effective and less toxic than amantadine. Ribavirin is the most recently approved antiviral agent for the treatment of respiratory syncytial virus infections. Numerous antiviral drugs are being studied in patients with acquired immunodeficiency syndrome. Although currently available drugs have improved our ability to manage a variety of viral illnesses, much needs to be learned about specific dosage guidelines based on the studies of pharmacokinetics, pharmacodynamics, potential adverse effects and viral resistance, and the role of combination therapy to optimize therapy.

scholarly journals Cell-Mediated Responses to Human Metapneumovirus Infection

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 542
Author(s):  
Marlies Ballegeer ◽  
Xavier Saelens
Keyword(s):  
Immune Response ◽  
Rna Virus ◽  
Cell Types ◽  
Host Immune Response ◽  
Human Metapneumovirus ◽  
Comprehensive Overview ◽  
Hmpv Infection ◽  
Life Threatening ◽  
Tract Infections ◽  
Almost All

Viruses are the most common cause of acute respiratory tract infections (ARTI). Human metapneumovirus (hMPV) frequently causes viral pneumonia which can become life-threatening if the virus spreads to the lungs. Even though hMPV was only isolated in 2001, this negative-stranded RNA virus has probably been circulating in the human population for many decades. Interestingly, almost all adults have serologic evidence of hMPV infection. A well-established host immune response is evoked when hMPV infection occurs. However, the virus has evolved to circumvent and even exploit the host immune response. Further, infection with hMPV induces a weak memory response, and re-infections during life are common. In this review, we provide a comprehensive overview of the different cell types involved in the immune response in order to better understand the immunopathology induced by hMPV. Such knowledge may contribute to the development of vaccines and therapeutics directed against hMPV.

scholarly journals Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

Pathogens ◽  
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.

scholarly journals Analysis of Porcine RIG-I Like Receptors Revealed the Positive Regulation of RIG-I and MDA5 by LGP2

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuangjie Li ◽  
Jie Yang ◽  
Yuanyuan Zhu ◽  
Hui Wang ◽  
Xingyu Ji ◽  
...  
Keyword(s):  
Cell Activation ◽  
Viral Infections ◽  
Rna Virus ◽  
Gene Knockout ◽  
Constitutive Activity ◽  
Virus Infections ◽  
Positive Regulation ◽  
Dsrna Binding ◽  
Livestock Animal ◽  
Signaling Activity

The RLRs play critical roles in sensing and fighting viral infections especially RNA virus infections. Despite the extensive studies on RLRs in humans and mice, there is a lack of systemic investigation of livestock animal RLRs. In this study, we characterized the porcine RLR members RIG-I, MDA5 and LGP2. Compared with their human counterparts, porcine RIG-I and MDA5 exhibited similar signaling activity to distinct dsRNA and viruses, via similar and cooperative recognitions. Porcine LGP2, without signaling activity, was found to positively regulate porcine RIG-I and MDA5 in transfected porcine alveolar macrophages (PAMs), gene knockout PAMs and PK-15 cells. Mechanistically, LGP2 interacts with RIG-I and MDA5 upon cell activation, and promotes the binding of dsRNA ligand by MDA5 as well as RIG-I. Accordingly, porcine LGP2 exerted broad antiviral functions. Intriguingly, we found that porcine LGP2 mutants with defects in ATPase and/or dsRNA binding present constitutive activity which are likely through RIG-I and MDA5. Our work provided significant insights into porcine innate immunity, species specificity and immune biology.

Mechanisms of Action of Ribavirin in Antiviral Therapies

2001 ◽  
Vol 12 (5) ◽  
pp. 261-272 ◽  
Author(s):  
Robert C Tam ◽  
Johnson YN Lau ◽  
Zhi Hong
Keyword(s):  
Hepatitis C ◽  
Viral Infections ◽  
Rna Virus ◽  
Lassa Fever ◽  
Biological Properties ◽  
Interferon Α ◽  
Hepatitis C Infection ◽  
Antiviral Activities ◽  
Syncytial Virus

Although ribavirin was originally synthesized over 30 years ago and has been used to treat viral infections as monotherapy (respiratory syncytial virus and Lassa fever virus) or with interferon-α (IFN-α) as combination therapy (hepatitis C virus), the precise mechanism of its therapeutic activities remains controversial. In this review we focus on two main biological properties of ribavirin: its indirect and direct antiviral activities (with particular emphasis on its efficacy against chronic hepatitis C infection). Each property could individually or collectively account for its clinical efficacy against viral infections. First, with emphasis on the evidence for indirect activities of ribavirin, we will review the clinical observations that suggest that the immunomodulatory properties of ribavirin can in part account for its antiviral activities in vivo. We will then describe the mode of ribavirin's direct antiviral activities. These direct activities can be ascribed to several possible mechanisms, including the recently described activity as an RNA mutagen, a property that may be important in driving a rapidly mutating RNA virus over the threshold to ‘error catastrophe′.

scholarly journals The Key Roles of Interferon Lambda in Human Molecular Defense against Respiratory Viral Infections

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 989
Author(s):  
Alexey A. Lozhkov ◽  
Sergey A. Klotchenko ◽  
Edward S. Ramsay ◽  
Herman D. Moshkoff ◽  
Dmitry A. Moshkoff ◽  
...  
Keyword(s):  
Immune Response ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Public Health Problem ◽  
Negative Influence ◽  
Epithelial Tissue ◽  
Major Public Health Problem ◽  
Type Iii ◽  
Respiratory Viral Infections ◽  
Type Iii Ifn

Interferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (MX1, OAS, IFITM1), and they have immuno-modulatory activities that shape adaptive immune responses. Unlike other IFN, the type III IFN signal through distinct receptors is limited to a few cell types, primarily mucosal epithelial cells. As a consequence of their greater and more durable production in nasal and respiratory tissues, they can determine the outcome of respiratory infections. This review is focused on the role of IFN-λ in the pathogenesis of respiratory viral infections, with influenza as a prime example. The influenza virus is a major public health problem, causing up to half a million lethal infections annually. Moreover, the virus has been the cause of four pandemics over the last century. Although IFN-λ are increasingly being tested in antiviral therapy, they can have a negative influence on epithelial tissue recovery and increase the risk of secondary bacterial infections. Therefore, IFN-λ expression deserves increased scrutiny as a key factor in the host immune response to infection.

scholarly journals Impact of Rhinovirus Infections in Children

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 521 ◽  
Author(s):  
Silvia Vandini ◽  
Carlotta Biagi ◽  
Maximilian Fischer ◽  
Marcello Lanari
Keyword(s):  
Rna Virus ◽  
Pediatric Population ◽  
Treatment Options ◽  
Respiratory Morbidity ◽  
Upper Respiratory Tract ◽  
Direct Cell ◽  
The Subject ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
Tract Infections

Rhinovirus (RV) is an RNA virus that causes more than 50% of upper respiratory tract infections in humans worldwide. Together with Respiratory Syncytial Virus, RV is one of the leading causes of viral bronchiolitis in infants and the most common virus associated with wheezing in children aged between one and two years. Because of its tremendous genetic diversity (>150 serotypes), the recurrence of RV infections each year is quite typical. Furthermore, because of its broad clinical spectrum, the clinical variability as well as the pathogenesis of RV infection are nowadays the subjects of an in-depth examination and have been the subject of several studies in the literature. In fact, the virus is responsible for direct cell cytotoxicity in only a small way, and it is now clearer than ever that it may act indirectly by triggering the release of active mediators by structural and inflammatory airway cells, causing the onset and/or the acute exacerbation of asthmatic events in predisposed children. In the present review, we aim to summarize the RV infection’s epidemiology, pathogenetic hypotheses, and available treatment options as well as its correlation with respiratory morbidity and mortality in the pediatric population.

scholarly journals Cytokines in the Nasal Washes of Children with Respiratory Syncytial Virus Bronchiolitis

2006 ◽  
Vol 19 (1) ◽  
pp. 205873920601900 ◽  
Author(s):  
F. Midulla ◽  
V. Tromba ◽  
L. LO Russo ◽  
F. Mileto ◽  
G. Sabatino ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Virus Infection ◽  
Lung Inflammation ◽  
Virus Infections ◽  
Nasal Wash ◽  
Respiratory Illnesses ◽  
Infected Infant ◽  
Cell Mediated Immune Response ◽  
Syncytial Virus

Although respiratory syncytial (RS) virus is the major cause of bronchiolitis and pneumonia in young children, the factors that regulate the associated lung inflammation have not been defined. The levels of interleukin (IL)10, IL-12, and interferon (IFN) were determined in the nasal wash samples from 20 infants with a clinical diagnosis of bronchiolitis, seven with confirmed RS virus infections and 9 control children without respiratory illnesses. IL-10 levels were significantly higher in acute nasal wash samples (1–4 d post-hospitalization) from RS virus- infected infants than in convalescent samples from these children (14–21 d post-hospitalization), from children with other forms of bronchiolitis and from control children. In contrast, only one RS virus-infected infant had detectable IL-12 in an acute nasal wash sample. IFN activity was not detected in any samples from RS virus-infected children. RS virus infection stimulates IL-10 expression but not IL-12 and IFN, possibly contributing to an ineffective cell-mediated immune response.

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