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Article ; Online: A novel anti-inflammatory treatment for bradykinin-induced sore throat or pharyngitis.

Leyva-Grado, Victor / Pugach, Pavel / Sadeghi-Latefi, Nazlie

Immunity, inflammation and disease

2021 Volume 9, Issue 4, Page(s) 1321–1335

Abstract: Background: Often thought of as a minor health concern, sore throat or pharyngitis is an important public health issue. It is one of the most common symptoms of upper respiratory diseases including COVID-19 and is a leading cause of physician visits and ...

Abstract	Background: Often thought of as a minor health concern, sore throat or pharyngitis is an important public health issue. It is one of the most common symptoms of upper respiratory diseases including COVID-19 and is a leading cause of physician visits and antibiotic prescriptions. However, few over-the-counter medications are proven to heal sore throat inflammation. Methods: Adenocarcinomic human alveolar basal epithelial cells (A549 cells) and three dimensional organotypic human respiratory tissues were used to study inflammation and various treatment effects on respiratory epithelia. The cells and tissues were studied both in the presence and absence of bradykinin, one of the first inflammatory mediators of pharyngitis. Inflammation was measured by analyzing the levels of prostaglandin E2 (PGE2), interleukin 8 (IL-8), and leukotriene B4 (LTB4), transepithelial electrical resistance (TEER), and lactate dehydrogenase (LDH) release. Tissue morphology was analyzed by immunohistochemistry. Results: In studying pharyngitis using organotypic human respiratory tissue stimulated with bradykinin, we saw an increase in PGE2 and interleukin-8 (IL-8) in response to bradykinin. Acetyl salicylic acid (ASA), a nonspecific COX inhibitor, was able to mitigate a bradykinin-induced increase in PGE2 in our studies. However, ASA was inflammatory above its therapeutic window, increasing the levels of PGE2 and IL-8 above those seen with bradykinin stimulation alone. We describe a novel, scientifically validated treatment for sore throat, that contains a low dose of ASA and other anti-inflammatory ingredients. Conclusion: This study elucidates the complex mechanisms involved in healing pharyngitis, an inflammatory condition of the upper respiratory epithelia. An ASA-based formula (Biovanta) mitigated bradykinin-induced inflammation more strongly than ASA alone in organotypic human respiratory tissues. Surprisingly, we found that many of the most common over the counter sore throat therapies exacerbate inflammation and IL-8 in organotypic human respiratory tissues, suggesting these common treatments may increase the likelihood of further respiratory complications.
MeSH term(s)	Anti-Inflammatory Agents/therapeutic use ; Bradykinin/pharmacology ; Bradykinin/therapeutic use ; COVID-19 ; Humans ; Pharyngitis/drug therapy ; SARS-CoV-2
Chemical Substances	Anti-Inflammatory Agents ; Bradykinin (S8TIM42R2W)
Language	English
Publishing date	2021-06-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2050-4527
ISSN (online)	2050-4527
DOI	10.1002/iid3.479
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections. LID - 1327

Behzadi Ma Fau - Leyva-Grado, Victor H. / Leyva-Grado, V. H.

Frontiers in Microbiology

Abstract: Emergence and re-emergence of respiratory virus infections represent a significant threat to global public health, as they occur seasonally and less frequently (such as in the case of influenza virus) as pandemic infections Some of these viruses have ... ...

Abstract	Emergence and re-emergence of respiratory virus infections represent a significant threat to global public health, as they occur seasonally and less frequently (such as in the case of influenza virus) as pandemic infections Some of these viruses have been in the human population for centuries and others had recently emerged as a public health problem Influenza viruses have been affecting the human population for a long time now;however, their ability to rapidly evolve through antigenic drift and antigenic shift causes the emergence of new strains A recent example of these events is the avian-origin H7N9 influenza virus outbreak currently undergoing in China Human H7N9 influenza viruses are resistant to amantadines and some strains are also resistant to neuraminidase inhibitors greatly limiting the options for treatment Respiratory syncytial virus (RSV) may cause a lower respiratory tract infection characterized by bronchiolitis and pneumonia mainly in children and the elderly Infection with RSV can cause severe disease and even death, imposing a severe burden for pediatric and geriatric health systems worldwide Treatment for RSV is mainly supportive since the only approved therapy, a monoclonal antibody, is recommended for prophylactic use in high-risk patients The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging respiratory virus The virus was first recognized in 2012 and it is associated with a lower respiratory tract disease that is more severe in patients with comorbidities No licensed vaccines or antivirals have been yet approved for the treatment of MERS-CoV in humans It is clear that the discovery and development of novel antivirals that can be used alone or in combination with existing therapies to treat these important respiratory viral infections are critical In this review, we will describe some of the novel therapeutics currently under development for the treatment of these infections FAU - Behzadi, Mohammad Amin
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #853955
Database	COVID19

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Article: Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections.

Behzadi, Mohammad Amin / Leyva-Grado, Victor H

Frontiers in microbiology

2019 Volume 10, Page(s) 1327

Abstract	Emergence and re-emergence of respiratory virus infections represent a significant threat to global public health, as they occur seasonally and less frequently (such as in the case of influenza virus) as pandemic infections. Some of these viruses have been in the human population for centuries and others had recently emerged as a public health problem. Influenza viruses have been affecting the human population for a long time now; however, their ability to rapidly evolve through antigenic drift and antigenic shift causes the emergence of new strains. A recent example of these events is the avian-origin H7N9 influenza virus outbreak currently undergoing in China. Human H7N9 influenza viruses are resistant to amantadines and some strains are also resistant to neuraminidase inhibitors greatly limiting the options for treatment. Respiratory syncytial virus (RSV) may cause a lower respiratory tract infection characterized by bronchiolitis and pneumonia mainly in children and the elderly. Infection with RSV can cause severe disease and even death, imposing a severe burden for pediatric and geriatric health systems worldwide. Treatment for RSV is mainly supportive since the only approved therapy, a monoclonal antibody, is recommended for prophylactic use in high-risk patients. The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging respiratory virus. The virus was first recognized in 2012 and it is associated with a lower respiratory tract disease that is more severe in patients with comorbidities. No licensed vaccines or antivirals have been yet approved for the treatment of MERS-CoV in humans. It is clear that the discovery and development of novel antivirals that can be used alone or in combination with existing therapies to treat these important respiratory viral infections are critical. In this review, we will describe some of the novel therapeutics currently under development for the treatment of these infections.
Keywords	covid19
Language	English
Publishing date	2019-06-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2019.01327
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Article ; Online: Rational drug design for sore throat—An aspirin-based treatment that addresses bradykinin-induced inflammation

Leyva-Grado, Victor / Pugach, Pavel / Latefi, Nazlie

bioRxiv

Abstract: Often thought of as a minor health concern, sore throat or pharyngitis is an important public health issue. It is one of the most common symptoms of upper respiratory diseases including COVID-19 and is a leading cause of physician visits and antibiotic ... ...

Abstract	Often thought of as a minor health concern, sore throat or pharyngitis is an important public health issue. It is one of the most common symptoms of upper respiratory diseases including COVID-19 and is a leading cause of physician visits and antibiotic prescriptions. Despite being on the market for decades, few over the counter sore throat medications are proven to heal sore throat. In studying pharyngitis using organotypic human respiratory tissue stimulated with bradykinin, we saw an increase in prostaglandin E2 (PGE2) and interleukin-8 (IL-8) in response to bradykinin. Bradykinin is one of the first inflammatory signals for pharyngitis and it increases PGE2 in human subjects. If left unregulated, PGE2 may further increase inflammation via the COX pathway and via IL-8, a proinflammatory chemokine responsible for neutrophil infiltration and possibly thus, a cytokine storm. Acetyl salicylic acid (ASA), a non-specific COX inhibitor, was able to mitigate a bradykinin-induced increase in PGE2 in our studies. However, ASA was inflammatory above its small therapeutic window, greatly increasing levels of PGE2 and IL-8 above those seen with bradykinin stimulation alone. Similar to other systems, the respiratory epithelia maintains a delicate balance of pro-inflammatory and anti-inflammatory signals in order to keep the respiratory barrier intact. To our knowledge, this is the first study to try and elucidate the complex mechanisms involved in healing pharyngitis, an inflammatory condition of the respiratory epithelia. Biovanta™, a formula containing ASA mitigated bradykinin-induced inflammation more strongly than ASA alone in organotypic human respiratory tissues. Surprisingly, we found that many of the most common over the counter sore throat therapies exacerbate inflammation and IL-8 in organotypic human respiratory tissues, suggesting these common treatments may possibly increase the likelihood of further respiratory complications in people.
Keywords	covid19
Publisher	BioRxiv
Document type	Article ; Online
DOI	10.1101/2020.11.06.370395
Database	COVID19

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Article ; Online: Aerosol administration increases the efficacy of oseltamivir for the treatment of mice infected with influenza viruses.

Leyva-Grado, Victor H / Palese, Peter

Antiviral research

2017 Volume 142, Page(s) 12–15

Abstract: Oseltamivir is an influenza neuraminidase inhibitor that along with supportive therapy has shown to help critically ill patients infected with H7N9 and H1N1pdm influenza virus strains to recover from disease. The standard of care recommends the ... ...

Abstract	Oseltamivir is an influenza neuraminidase inhibitor that along with supportive therapy has shown to help critically ill patients infected with H7N9 and H1N1pdm influenza virus strains to recover from disease. The standard of care recommends the administration of oseltamivir via oral route which represents difficulties in patients with gastrointestinal complications. Here we tested the use of aerosol administration of oseltamivir to treat mice infected with influenza A/H7N9 virus or influenza A/H1N1pdm virus and directly compared this approach to the standard of care, oral administration. Using nose only delivery of aerosolized oseltamivir we observed a significant increase in efficacy of the treatment compared to oral administration characterized by reduced body weight loss, increased survival rate and dose sparing. The preclinical data presented here supports the possibility of using this approach in clinical settings.
Language	English
Publishing date	2017-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2017.03.002
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Zs.A 1627: Show issues

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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: An Influenza Virus Entry Inhibitor Targets Class II PI3 Kinase and Synergizes with Oseltamivir.

O'Hanlon, Ryan / Leyva-Grado, Victor H / Sourisseau, Marion / Evans, Matthew J / Shaw, Megan L

ACS infectious diseases

2019 Volume 5, Issue 10, Page(s) 1779–1793

Abstract: Two classes of antivirals targeting the viral neuraminidase (NA) and endonuclease are currently the only clinically useful drugs for the treatment of influenza. However, resistance to both antivirals has been observed in clinical isolates, and there was ... ...

Abstract	Two classes of antivirals targeting the viral neuraminidase (NA) and endonuclease are currently the only clinically useful drugs for the treatment of influenza. However, resistance to both antivirals has been observed in clinical isolates, and there was widespread resistance to oseltamivir (an NA inhibitor) among H1N1 viruses prior to 2009. This potential for resistance and lack of diversity for antiviral targets highlights the need for new influenza antivirals with a higher barrier to resistance. In this study, we identified an antiviral compound, M85, that targets host kinases, epidermal growth factor receptor (EGFR), and phosphoinositide 3 class II β (PIK3C2β) and is not susceptible to resistance by viral mutations. M85 blocks endocytosis of influenza viruses and inhibits a broad-spectrum of viruses with minimal cytotoxicity.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Cell Line ; Chlorocebus aethiops ; Class II Phosphatidylinositol 3-Kinases/drug effects ; Disease Models, Animal ; Drug Combinations ; Drug Evaluation, Preclinical ; Drug Resistance, Viral/drug effects ; Drug Synergism ; Enzyme Inhibitors/pharmacology ; ErbB Receptors ; Female ; Humans ; Influenza A Virus, H1N1 Subtype/drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae/drug effects ; Oseltamivir/pharmacology ; Phosphatidylinositol 3-Kinases/drug effects ; Vero Cells ; Virus Internalization/drug effects
Chemical Substances	Antiviral Agents ; Drug Combinations ; Enzyme Inhibitors ; Oseltamivir (20O93L6F9H) ; Class II Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; Pik3c2b protein, mouse (EC 2.7.1.137) ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2019-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2373-8227
ISSN (online)	2373-8227
DOI	10.1021/acsinfecdis.9b00230
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Article ; Online: A single-shot adenoviral vaccine provides hemagglutinin stalk-mediated protection against heterosubtypic influenza challenge in mice.

Bliss, Carly M / Freyn, Alec W / Caniels, Tom G / Leyva-Grado, Victor H / Nachbagauer, Raffael / Sun, Weina / Tan, Gene S / Gillespie, Virginia L / McMahon, Meagan / Krammer, Florian / Hill, Adrian V S / Palese, Peter / Coughlan, Lynda

Molecular therapy : the journal of the American Society of Gene Therapy

2022 Volume 30, Issue 5, Page(s) 2024–2047

Abstract: Conventional influenza vaccines fail to confer broad protection against diverse influenza A viruses with pandemic potential. Efforts to develop a universal influenza virus vaccine include refocusing immunity towards the highly conserved stalk domain of ... ...

Abstract	Conventional influenza vaccines fail to confer broad protection against diverse influenza A viruses with pandemic potential. Efforts to develop a universal influenza virus vaccine include refocusing immunity towards the highly conserved stalk domain of the influenza virus surface glycoprotein, hemagglutinin (HA). We constructed a non-replicating adenoviral (Ad) vector, encoding a secreted form of H1 HA, to evaluate HA stalk-focused immunity. The Ad5_H1 vaccine was tested in mice for its ability to elicit broad, cross-reactive protection against homologous, heterologous, and heterosubtypic lethal challenge in a single-shot immunization regimen. Ad5_H1 elicited hemagglutination inhibition (HI
MeSH term(s)	Adenoviridae/genetics ; Animals ; Antibodies, Viral ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Hemagglutinins ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza A Virus, H5N1 Subtype/genetics ; Influenza A virus ; Influenza Vaccines ; Influenza, Human/prevention & control ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections
Chemical Substances	Antibodies, Viral ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins ; Influenza Vaccines
Language	English
Publishing date	2022-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2022.01.011
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Zs.A 5640: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Seroprevalence of viral hepatitis A, B, C, D and E viruses in the Hormozgan province southern Iran.

Behzadi, Mohammad Amin / Leyva-Grado, Victor Hugo / Namayandeh, Mandana / Ziyaeyan, Atoosa / Feyznezhad, Roya / Dorzaban, Hedayat / Jamalidoust, Marzieh / Ziyaeyan, Mazyar

BMC infectious diseases

2019 Volume 19, Issue 1, Page(s) 1027

Abstract: Background: Viral hepatitis is a global public health problem affecting millions of people worldwide, causing thousands of deaths due to acute and persistent infection, cirrhosis, and liver cancer. Providing updated serologic data can improve both ... ...

Abstract	Background: Viral hepatitis is a global public health problem affecting millions of people worldwide, causing thousands of deaths due to acute and persistent infection, cirrhosis, and liver cancer. Providing updated serologic data can improve both surveillance and disease control programs. This study is aimed to determine the seroprevalence of markers for viral hepatitis (A, B, C, D and E) and the epidemiology of such infections in the general population of southern Iran's Hormozgan province. Methods: Between 2016 and 2017, a total of 562 individuals with ages ranging from 1 to 86 years, who visited governmental public laboratories for routine check-ups, were tested for the presence of serological markers to hepatitis virus types A to E using enzyme-linked immunosorbent assays. Results: The overall anti-hepatitis A virus (HAV) antibody seroprevalence was 93.2% (524/562). The prevalence of anti-hepatitis E virus (HEV) antibodies was 15.8% (89/562) among which 1.6% (9/562) of the seropositive individuals also had evidence of recent exposure to the virus (IgM positivity). Two and a half percent (14/562) were positive for hepatitis B surface (HBs) antigen, whereas 11.6% (65/562) tested positive for anti-hepatitis B core (HBc) antibodies. Among anti-HBc positive patients, 11% (7/65) had HBs Ag and 5% (3/65) were positive for anti-hepatitis D virus (HDV) antibodies. The prevalence of anti-hepatitis C virus (HCV) antibodies was 0.7% (4/562). The seroprevalence of anti-HAV, HEV IgG, anti-HBc antibodies, and HBs Ag increased with age. Conclusion: The present study confirms a high seroprevalence of HAV infection among the examined population and reveals high levels of endemicity for HEV in the region. Planned vaccination policies against HAV should be considered in all parts of Iran. In addition, improvements on public sanitation and hygiene management of drinking water sources for the studied area are recommended.
MeSH term(s)	Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers/blood ; Child ; Child, Preschool ; Cross-Sectional Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Hepatitis Antibodies/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/immunology ; Hepatitis Viruses/immunology ; Hepatitis, Viral, Human/epidemiology ; Hepatitis, Viral, Human/immunology ; Hepatitis, Viral, Human/prevention & control ; Humans ; Infant ; Iran/epidemiology ; Male ; Middle Aged ; Prevalence ; Seroepidemiologic Studies ; Vaccination ; Young Adult
Chemical Substances	Biomarkers ; Hepatitis Antibodies ; Hepatitis B Surface Antigens
Language	English
Publishing date	2019-12-03
Publishing country	England
Document type	Journal Article
ISSN	1471-2334
ISSN (online)	1471-2334
DOI	10.1186/s12879-019-4661-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Direct administration in the respiratory tract improves efficacy of broadly neutralizing anti-influenza virus monoclonal antibodies.

Leyva-Grado, Victor H / Tan, Gene S / Leon, Paul E / Yondola, Mark / Palese, Peter

Antimicrobial agents and chemotherapy

2015 Volume 59, Issue 7, Page(s) 4162–4172

Abstract: The emergence of influenza virus strains resistant to approved neuraminidase inhibitors and the time constrains after infection when these drugs can be effective constitute major drawbacks for this class of drugs. This highlights a critical need to ... ...

Abstract	The emergence of influenza virus strains resistant to approved neuraminidase inhibitors and the time constrains after infection when these drugs can be effective constitute major drawbacks for this class of drugs. This highlights a critical need to discover new therapeutic agents that can be used for the treatment of influenza virus-infected patients. The use of broadly neutralizing anti-influenza monoclonal antibodies (MAbs) has been sought as an alternative immunotherapy against influenza infection. Here, we tested in mice previously characterized broadly neutralizing anti-hemagglutinin (HA) stalk MAbs prophylactically and therapeutically using different routes of administration. The efficacy of treatment against an influenza H1N1 pandemic virus challenge was compared between two systemic routes of administration, intraperitoneal (i.p.) and intravenous (i.v.), and two local routes, intranasal (i.n.) and aerosol (a.e.). The dose of MAb required for prophylactic protection was reduced by 10-fold in animals treated locally (i.n. or a.e.) compared with those treated systemically (i.p. or i.v.). Improved therapeutic protection was observed in animals treated i.n. on day 5 postinfection (60% survival) compared with those treated via the i.p. route (20% survival). An increase in therapeutic efficacy against other influenza virus subtypes (H5N1) was also observed when a local route of administration was used. Our findings demonstrate that local administration significantly decreases the amount of broadly neutralizing monoclonal antibody required for protection against influenza, which highlights the potential use of MAbs as a therapeutic agent for influenza-associated disease.
MeSH term(s)	Administration, Intranasal ; Administration, Intravenous ; Aerosols ; Animals ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/administration & dosage ; Antibodies, Neutralizing/therapeutic use ; Antiviral Agents/administration & dosage ; Antiviral Agents/pharmacokinetics ; Antiviral Agents/therapeutic use ; Biological Availability ; Female ; Hemagglutinins/immunology ; Humans ; Influenza A Virus, H1N1 Subtype/drug effects ; Influenza A Virus, H5N1 Subtype/drug effects ; Influenza, Human/drug therapy ; Influenza, Human/pathology ; Influenza, Human/virology ; Injections, Intraperitoneal ; Lung/pathology ; Lung/virology ; Mice ; Mice, Inbred BALB C ; Tissue Distribution
Chemical Substances	Aerosols ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antiviral Agents ; Hemagglutinins
Language	English
Publishing date	2015-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/AAC.00290-15
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 809: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Einzelsignatur: Show issues

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Article ; Online: Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection.

Leyva-Grado, Victor H / Ermler, Megan E / Schotsaert, Michael / Gonzalez, Ma G / Gillespie, Virginia / Lim, Jean K / García-Sastre, Adolfo

mBio

2017 Volume 8, Issue 2

Abstract: An exacerbated immune response is one of the main causes of influenza-induced lung damage during infection. The molecular mechanisms regulating the fate of the initial immune response to infection, either as a protective response or as detrimental ... ...

Abstract	An exacerbated immune response is one of the main causes of influenza-induced lung damage during infection. The molecular mechanisms regulating the fate of the initial immune response to infection, either as a protective response or as detrimental immunopathology, are not well understood. The purinergic receptor P2X7 is an ionotropic nucleotide-gated ion channel receptor expressed on immune cells that has been implicated in induction and maintenance of excessive inflammation. Here, we analyze the role of this receptor in a mouse model of influenza virus infection using a receptor knockout (KO) mouse strain. Our results demonstrate that the absence of the P2X7 receptor results in a better outcome to influenza virus infection characterized by reduced weight loss and increased survival upon experimental influenza challenge compared to wild-type mice. This effect was not virus strain specific. Overall lung pathology and apoptosis were reduced in virus-infected KO mice. Production of proinflammatory cytokines and chemokines such as interleukin-10 (IL-10), gamma interferon (IFN-γ), and CC chemokine ligand 2 (CCL2) was also reduced in the lungs of the infected KO mice. Infiltration of neutrophils and depletion of CD11b
MeSH term(s)	Animals ; Body Weight ; Cytokines/analysis ; Disease Models, Animal ; Host-Pathogen Interactions ; Lung/pathology ; Macrophages/immunology ; Mice ; Mice, Knockout ; Neutrophils/immunology ; Orthomyxoviridae/pathogenicity ; Orthomyxoviridae Infections/pathology ; Orthomyxoviridae Infections/virology ; Receptors, Purinergic P2X7/metabolism ; Survival Analysis
Chemical Substances	Cytokines ; Receptors, Purinergic P2X7
Keywords	covid19
Language	English
Publishing date	2017-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.00229-17
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