scholarly journals Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Min Yee ◽  
E. David Cohen ◽  
Jeannie Haak ◽  
Andrew M. Dylag ◽  
Michael A. O’Reilly
Keyword(s):  
Lung Disease ◽  
Influenza A ◽  
Viral Infections ◽  
The Elderly ◽  
Virus Infections ◽  
Mitochondrial Superoxide ◽  
Adult Mice ◽  
Club Cells ◽  
Age Dependent ◽  
Neonatal Hyperoxia

AbstractThe severity of COVID-19 lung disease is higher in the elderly and people with pre-existing co-morbidities. People who were born preterm may be at greater risk for COVID-19 because their early exposure to oxygen (hyperoxia) at birth increases the severity of respiratory viral infections. Hyperoxia at birth increases the severity of influenza A virus infections in adult mice by reducing the number of alveolar epithelial type 2 (AT2) cells. Since AT2 cells express the SARS-CoV-2 receptors angiotensin converting enzyme (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2), their expression should decline as AT2 cells are depleted by hyperoxia. Instead, ACE2 was detected in airway Club cells and endothelial cells at birth, and then AT2 cells at one year of age. Neonatal hyperoxia stimulated expression of ACE2 in Club cells and in AT2 cells by 2 months of age. It also stimulated expression of TMPRSS2 in the lung. Increased expression of SARS-CoV-2 receptors was blocked by mitoTEMPO, a mitochondrial superoxide scavenger that reduced oxidative stress and DNA damage seen in oxygen-exposed mice. Our finding that hyperoxia enhances the age-dependent expression of SARS-CoV-2 receptors in mice helps explain why COVID-19 lung disease is greater in the elderly and people with pre-existing co-morbidities.

scholarly journals Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice

2020 ◽  
Author(s):  
Min Yee ◽  
E. David Cohen ◽  
Jeannie Haak ◽  
Andrew M. Dylag ◽  
Michael A. O’Reilly
Keyword(s):  
Lung Disease ◽  
Influenza A ◽  
The Elderly ◽  
Virus Infections ◽  
Alveolar Epithelial ◽  
Mitochondrial Superoxide ◽  
Adult Mice ◽  
Club Cells ◽  
Age Dependent ◽  
Neonatal Hyperoxia

ABSTRACTThe severity of COVID-19 lung disease is higher in the elderly and people with pre-existing co-morbidities. People who were born preterm may be at greater risk for COVID-19 because their early exposure to oxygen at birth increases their risk of being hospitalized when infected with RSV and other respiratory viruses. Our prior studies in mice showed how high levels of oxygen (hyperoxia) between postnatal days 0-4 increases the severity of influenza A virus infections by reducing the number of alveolar epithelial type 2 (AT2) cells. Because AT2 cells express the SARS-CoV-2 receptors angiotensin converting enzyme (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2), we expected their expression would decline as AT2 cells were depleted by hyperoxia. Instead, we made the surprising discovery that expression of Ace2 and Tmprss2 mRNA increases as mice age and is accelerated by exposing mice to neonatal hyperoxia. ACE2 is primarily expressed at birth by airway Club cells and becomes detectable in AT2 cells by one year of life. Neonatal hyperoxia increases ACE2 expression in Club cells and makes it detectable in 2-month-old AT2 cells. This early and increased expression of SARS-CoV-2 receptors was not seen in adult mice who had been administered the mitochondrial superoxide scavenger mitoTEMPO during hyperoxia. Our finding that early life insults such as hyperoxia enhances the age-dependent expression of SARS-CoV-2 receptors in the respiratory epithelium helps explain why COVID-19 lung disease is greater in the elderly and people with pre-existing co-morbidities.

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 Low Dose Hyperoxia Primes Airways for Fibrosis in Mice after Influenza A Infection

2020 ◽  
Author(s):  
Andrew M. Dylag ◽  
Jeannie Haak ◽  
Rachel Warren ◽  
Min Yee ◽  
Gloria S. Pryhuber ◽  
...  
Keyword(s):  
Lung Function ◽  
Viral Infection ◽  
Preterm Infants ◽  
Influenza A ◽  
Low Dose ◽  
Viral Infections ◽  
Airway Hyperreactivity ◽  
Normal Lung ◽  
High Dose ◽  
Neonatal Hyperoxia

AbstractIt is well known that supplemental oxygen used to treat preterm infants in respiratory distress is associated with permanently disrupting lung development and the host response to influenza A virus (IAV). However, many infants who go home with normally functioning lungs are also at risk for hyperreactivity after a respiratory viral infection suggesting neonatal oxygen may have induced hidden molecular changes that may prime to the lung for disease. We discovered that thrombospondin-1 (TSP-1) is elevated in adult mice exposed to high-dose neonatal hyperoxia that is known to cause alveolar simplification and fibrotic lung disease following IAV infection. TSP-1 was also elevated in a new, low-dose hyperoxia mouse model (40% for 8 days; 40×8) that we recently reported causes a transient change in lung function that resolves by 8 weeks of age. Elevated TSP-1 was also identified in human autopsy samples of BPD-affected former preterm infants. Consistent with TSP-1 being a master TGFβ regulator, an early transient activation of TGFβ signaling, increased airway hyperreactivity, and peribronchial inflammation and fibrosis were seen when 40×8 mice were infected with IAV, which was not seen in infected room air controls. These findings reveal low dose of neonatal hyperoxia that does not affect lung function or structure may still change expression of genes, such as TSP-1, that may prime the lung for disease following respiratory viral infections, and may help explain why former preterm infants who have normal lung function are susceptible to airway obstruction and increased morbidity after viral infection.

Changes in lung permeability and lung mechanics accompany homeostatic instability in senescent mice

2003 ◽  
Vol 95 (4) ◽  
pp. 1681-1687 ◽  
Author(s):  
Clarke G. Tankersley ◽  
Jessica A. Shank ◽  
Susan E. Flanders ◽  
Shawn E. Soutiere ◽  
Richard Rabold ◽  
...  
Keyword(s):  
Lung Disease ◽  
Lung Volume ◽  
Inbred Mouse ◽  
Body Weight Loss ◽  
The Elderly ◽  
Lung Mechanics ◽  
Barrier Dysfunction ◽  
Lung Permeability ◽  
Age Dependent ◽  
Imminent Death

Aging and lung disease are recognized factors that increase mortality risk in subjects exposed to ambient particulate matter (PM). In an effort to understand the mechanisms of enhanced susceptibility, the present study examined an inbred mouse model of senescence to 1) determine changes in lung permeability as animals approach the end-of-life and 2) characterize age-dependent changes in lung mechanics in presenescent and terminally senescent mice. The clearance of technetium-99m (99mTc)-diethylenetriamine pentaacetic acid (DTPA) was used to test the hypothesis that lung permeability increases with age and enhances uptake of soluble components of PM principally during the period several weeks before death in AKR/J mice. Quasistatic pressure-volume curves were conducted on robust and on terminally senescent AKR/J mice several weeks before death to assess the relative importance of lung mechanics. Abrupt body weight loss was used to signal imminent death because it accompanies indexes of physiological aging and terminal senescence. 99mTc-DTPA clearance from the lung 30 min after tracheal instillation was significantly ( P < 0.05) enhanced in senescent mice. Age-dependent changes in lung mechanics were indicative of significant ( P < 0.05) decrements in lung volume and compliance several weeks before death. Thus, during a period of homeostatic instability leading toward natural death, AKR/J mice showed enhanced permeability of soluble particles despite a decrease in lung volume and concomitant alveolar surface area. These results suggest that pulmonary epithelial-endothelial barrier dysfunction occurs in terminally senescent mice just before death. Furthermore, this senescent-dependent increase in lung permeability may be a contributing factor for increased PM susceptibility in the elderly and patients with lung disease.

scholarly journals Neonatal hyperoxia depletes pulmonary vein cardiomyocytes in adult mice via mitochondrial oxidation

2018 ◽  
Vol 314 (5) ◽  
pp. L846-L859 ◽  
Author(s):  
Min Yee ◽  
Ethan David Cohen ◽  
William Domm ◽  
George A. Porter ◽  
Andrew N. McDavid ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Pulmonary Vein ◽  
Supplemental Oxygen ◽  
Genetic Lineage ◽  
Mitochondrial Superoxide ◽  
Adult Mice ◽  
Capillary Rarefaction ◽  
Muscle Genes ◽  
Lineage Mapping ◽  
Neonatal Hyperoxia

Supplemental oxygen given to preterm infants has been associated with permanently altering postnatal lung development. Now that these individuals are reaching adulthood, there is growing concern that early life oxygen exposure may also promote cardiovascular disease through poorly understood mechanisms. We previously reported that adult mice exposed to 100% oxygen between postnatal days 0 and 4 develop pulmonary hypertension, defined pathologically by capillary rarefaction, dilation of arterioles and veins, cardiac failure, and a reduced lifespan. Here, Affymetrix Gene Arrays are used to identify early transcriptional changes that take place in the lung before pulmonary capillary rarefaction. We discovered neonatal hyperoxia reduced expression of cardiac muscle genes, including those involved in contraction, calcium signaling, mitochondrial respiration, and vasodilation. Quantitative RT-PCR, immunohistochemistry, and genetic lineage mapping using Myh6CreER; Rosa26RmT/mG mice revealed this reflected loss of pulmonary vein cardiomyocytes. The greatest loss of cadiomyocytes was seen within the lung followed by a graded loss beginning at the hilum and extending into the left atrium. Loss of these cells was seen by 2 wk of age in mice exposed to ≥80% oxygen and was attributed, in part, to reduced proliferation. Administering mitoTEMPO, a scavenger of mitochondrial superoxide during neonatal hyperoxia prevented loss of these cells. Since pulmonary vein cardiomyocytes help pump oxygen-rich blood out of the lung, their early loss following neonatal hyperoxia may contribute to cardiovascular disease seen in these mice, and perhaps in people who were born preterm.

ABC of viral infections in hematology: focus on herpesviruses

2019 ◽  
Vol 50 (3) ◽  
pp. 159-166 ◽  
Author(s):  
Jan Styczyński
Keyword(s):  
Host Cell ◽  
Influenza A ◽  
Hematopoietic Cell Transplantation ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Point Of View ◽  
Virus Infections ◽  
Dna Viruses ◽  
Form Of Life ◽  
Syncytial Virus

AbstractViruses are a form of life that possess genes but do not have a cellular structure. Viruses do not have their own metabolism, and they require a host cell to make new products; therefore, they cannot naturally reproduce outside a host cell. The objective of this paper is to present the basic practical clinical roles of viruses in patients with hematological diseases including malignancies and non-malignan- cies, as well as those undergoing hematopoietic cell transplantation (HCT), with the focus on herpesviruses causing latent infections in severely immunocompromised patients. From the hematologist point of view, viruses can play a major role in four conditions: causing infections; causing lymphoproliferations and/or malignancies; causing (pan)cytopenia; and used as vectors in treatment (e.g., gene therapy, CAR-T cells). Taking into account the role of viruses in hematology, infection is the most frequent condition. Among DNA viruses, the highest morbidity potential for human is expressed by Herpesviridiae (herpesviruses), Adenoviridae (adenovirus; ADV), Polyomavirus (BKV, JCV), and Bocavirus. RNA viruses can play a role in pathogenesis of different clinical conditions and diseases: lymphoproliferative disorders and malignancy, possibly causing NHL, AML, MDS, and others (HCV, HIV, and others); pancytopenia and aplastic anemia (HIV, HCV, Dengue virus); respiratory infections (community-acquired respiratory virus infections; CARV) caused by Orthomyxoviruses (e.g. influenza A/B), Paramyxoviruses (e.g. human parainfluenza virus PIV-1, -2, -3, and -4; respiratory syncytial virus RSV-A and -B), picornaviruses (e.g., human rhinovirus), coronaviruses (e.g., human coronavirus), Pneumoviridiae (e.g., human metapneumovirus), and potentially other viruses.

scholarly journals Neonatal hyperoxia alters the host response to influenza A virus infection in adult mice through multiple pathways

2013 ◽  
Vol 305 (4) ◽  
pp. L282-L290 ◽  
Author(s):  
Bradley W. Buczynski ◽  
Min Yee ◽  
Kyle C. Martin ◽  
B. Paige Lawrence ◽  
Michael A. O'Reilly
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Lung Development ◽  
Host Response ◽  
Influenza A ◽  
Leukocyte Recruitment ◽  
Newborn Mice ◽  
Adult Mice ◽  
Influenza A Virus Infection ◽  
Neonatal Hyperoxia

Exposing preterm infants or newborn mice to high concentrations of oxygen disrupts lung development and alters the response to respiratory viral infections later in life. Superoxide dismutase (SOD) has been separately shown to mitigate hyperoxia-mediated changes in lung development and attenuate virus-mediated lung inflammation. However, its potential to protect adult mice exposed to hyperoxia as neonates against viral infection is not known. Here, transgenic mice overexpressing extracellular (EC)-SOD in alveolar type II epithelial cells are used to test whether SOD can alleviate the deviant pulmonary response to influenza virus infection in adult mice exposed to hyperoxia as neonates. Fibrotic lung disease, observed following infection in wild-type (WT) mice exposed to hyperoxia as neonates, was prevented by overexpression of EC-SOD. However, leukocyte recruitment remained excessive, and levels of monocyte chemoattractant protein (MCP)-1 remained modestly elevated following infection in EC-SOD Tg mice exposed to hyperoxia as neonates. Because MCP-1 is often associated with pulmonary inflammation and fibrosis, the host response to infection was concurrently evaluated in adult Mcp-1 WT and Mcp-1 knockout mice exposed to neonatal hyperoxia. In contrast to EC-SOD, excessive leukocyte recruitment, but not lung fibrosis, was dependent upon MCP-1. Our findings demonstrate that neonatal hyperoxia alters the inflammatory and fibrotic responses to influenza A virus infection through different pathways. Therefore, these data suggest that multiple therapeutic strategies may be needed to provide complete protection against diseases attributed to prematurity and early life exposure to oxygen.

scholarly journals Transcriptome Analyses Implicate Endogenous Retroviruses Involved in the Host Antiviral Immune System through the Interferon Pathway

2021 ◽  
Author(s):  
Miao Wang ◽  
Liying Wang ◽  
Haizhou Liu ◽  
Jianjun Chen ◽  
Di Liu
Keyword(s):  
Transcriptional Activation ◽  
Measles Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Endogenous Retroviruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Published Data ◽  
Virus Infections ◽  
Antiviral Immune Response

AbstractHuman endogenous retroviruses (HERVs) are the remains of ancient retroviruses that invaded our ancestors’ germline cell and were integrated into the genome. The expression of HERVs has always been a cause for concern because of its association with various cancers and diseases. However, few previous studies have focused on specific activation of HERVs by viral infections. Our previous study has shown that dengue virus type 2 (DENV-2) infection induces the transcription of a large number of abnormal HERVs loci; therefore, the purpose of this study was to explore the relationship between exogenous viral infection and HERV activation further. In this study, we retrieved and reanalyzed published data on 21 transcriptomes of human cells infected with various viruses. We found that infection with different viruses could induce transcriptional activation of HERV loci. Through the comparative analysis of all viral datasets, we identified 43 key HERV loci that were up-regulated by DENV-2, influenza A virus, influenza B virus, Zika virus, measles virus, and West Nile virus infections. Furthermore, the neighboring genes of these HERVs were simultaneously up-regulated, and almost all such neighboring genes were interferon-stimulated genes (ISGs), which are enriched in the host’s antiviral immune response pathways. Our data supported the hypothesis that activation of HERVs, probably via an interferon-mediated mechanism, plays an important role in innate immunity against viral infections.

scholarly journals “Tiryaq Arba” (a Polyherbal Unani Formulation) as Prophylactic Medicine Against Epidemics of Acute Respiratory Viral Infections

2020 ◽  
Vol 7 (3) ◽  
Author(s):  
Shabnam Ansari ◽  
Ijhar Ahmad ◽  
Mahboob Ali ◽  
Mohd. Maaz
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Antioxidant Properties ◽  
Parainfluenza Virus ◽  
Virus Infections ◽  
Gentiana Lutea ◽  
Respiratory Viral Infections ◽  
Syncytial Virus ◽  
Type 3

: “Tiryaq Arba” is a polyherbal Unani formulation in a majoon dosage form that contains four herbal ingredients, namely habbul ghar (Laurus nobilis), juntiyana romi (Gentiana lutea), murr maki (Commiphora myrrha), and zarawand taweel (Aristolochia longa). The medicine has been used as an antidote against different poisons and as a prophylactic medicine before and/or during epidemics. The constituents have been proposed to act as anti-infective, anti-microbial, and antidote against various infectious agents during epidemics (waba). Scientific experimentation of the above-mentioned constituents has also reinforced their beneficial antiviral, immunomodulatory, and antioxidant properties against epidemics of acute respiratory viral infections such as; severe acute respiratory syndrome coronavirus (SARS-CoV), adenovirus, influenza and influenza A virus, respiratory syncytial virus infections, parainfluenza virus, human rhinovirus B, coxsackievirus, parainfluenza virus type 3, Newcastle disease virus, and influenza A virus, which are a greater cause for morbidity and mortality faced by the world, earlier and at present.

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