scholarly journals Pulmonary transcriptomic responses indicate a dual role of inflammation in pneumonia development and viral clearance during 2009 pandemic influenza infection

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3915 ◽  
Author(s):  
Raquel Almansa ◽  
Pamela Martínez-Orellana ◽  
Lucía Rico ◽  
Verónica Iglesias ◽  
Alicia Ortega ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Pandemic Influenza ◽  
Dual Role ◽  
Viral Clearance ◽  
Cytokine Signaling ◽  
Effective Response ◽  
Pdm09 Virus ◽  
Influenza A H1n1

Background The interaction between influenza virus and the host response to infection clearly plays an important role in determining the outcome of infection. While much is known on the participation of inflammation on the pathogenesis of severe A (H1N1) pandemic 09-influenza virus, its role in the course of non-fatal pneumonia has not been fully addressed. Methods A systems biology approach was used to define gene expression profiles, histology and viral dynamics in the lungs of healthy immune-competent mice with pneumonia caused by a human influenza A (H1N1) pdm09 virus, which successfully resolved the infection. Results Viral infection activated a marked pro-inflammatory response at the lung level paralleling the emergence of histological changes. Cellular immune response and cytokine signaling were the two signaling pathway categories more representative of our analysis. This transcriptome response was associated to viral clearance, and its resolution was accompanied by resolution of histopathology. Discussion These findings suggest a dual role of pulmonary inflammation in viral clearance and development of pneumonia during non-fatal infection caused by the 2009 pandemic influenza virus. Understanding the dynamics of the host’s transcriptomic and virological changes over the course of the infection caused by A (H1N1) pdm09 virus may help identifying the immune response profiles associated with an effective response against influenza virus.

scholarly journals In Vitro and In Vivo Characterization of Novel Neuraminidase Substitutions in Influenza A(H1N1)pdm09 Virus Identified Using Laninamivir-Mediated In Vitro Selection

2019 ◽  
Vol 93 (6) ◽  
Author(s):  
Khristine Kaith S. Lloren ◽  
Jin Jung Kwon ◽  
Won-Suk Choi ◽  
Ju Hwan Jeong ◽  
Su Jeong Ahn ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Deep Sequencing ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Viral Fitness ◽  
Pdm09 Virus ◽  
Influenza A H1n1 ◽  
Na Gene

ABSTRACT Neuraminidase (NA) inhibitors (NAIs) are widely used antiviral drugs for the treatment of humans with influenza virus infections. There have been widespread reports of NAI resistance among seasonal A(H1N1) viruses, and most have been identified in oseltamivir-exposed patients or those treated with other NAIs. Thus, monitoring and identifying NA markers conferring resistance to NAIs—particularly newly introduced treatments—are critical to the management of viral infections. Therefore, we screened and identified substitutions conferring resistance to laninamivir by enriching random mutations in the NA gene of the 2009 pandemic influenza [A(H1N1)pdm09] virus followed by deep sequencing of the laninamivir-selected variants. After the generation of single mutants possessing each identified mutation, two A(H1N1)pdm09 recombinants possessing novel NA gene substitutions (i.e., D199E and P458T) were shown to exhibit resistance to more than one NAI. Of note, mutants possessing P458T—which is located outside of the catalytic or framework residue of the NA active site—exhibited highly reduced inhibition by all four approved NAIs. Using MDCK cells, we observed that the in vitro viral replication of the two recombinants was lower than that of the wild type (WT). Additionally, in infected mice, decreased mortality and/or mean lung viral titers were observed in mutants compared with the WT. Reverse mutations to the WT were observed in lung homogenate samples from D199E-infected mice after 3 serial passages. Overall, the novel NA substitutions identified could possibly emerge in influenza A(H1N1)pdm09 viruses during laninamivir therapy and the viruses could have altered NAI susceptibility, but the compromised in vitro/in vivo viral fitness may limit viral spreading. IMPORTANCE With the widespread emergence of NAI-resistant influenza virus strains, continuous monitoring of mutations that confer antiviral resistance is needed. Laninamivir is the most recently approved NAI in several countries; few data exist related to the in vitro selection of viral mutations conferring resistance to laninamivir. Thus, we screened and identified substitutions conferring resistance to laninamivir by random mutagenesis of the NA gene of the 2009 pandemic influenza [A(H1N1)pdm09] virus strain followed by deep sequencing of the laninamivir-selected variants. We found several novel substitutions in NA (D199E and P458T) in an A(H1N1)pdm09 background which conferred resistance to NAIs and which had an impact on viral fitness. Our study highlights the importance of continued surveillance for potential antiviral-resistant variants and the development of alternative therapeutics.

scholarly journals EVOLUTION OF PANDEMIC INFLUENZA VIRUS A(H1N1)PDM09 IN 2009-2016: DYNAMICS OF RECEPTOR SPECIFICITY OF THE FIRST HEMAGGLUTININ SUBUNIT (HA1)

2019 ◽  
Vol 64 (2) ◽  
pp. 63-72 ◽  
Author(s):  
D. K. Lvov ◽  
V. S. Bogdanova ◽  
I. M. Kirillov ◽  
M. Yu. Shchelkanov ◽  
E. I. Burtseva ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Russian Federation ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Incidence Rates ◽  
Receptor Specificity ◽  
Human Respiratory Tract ◽  
Pdm09 Virus ◽  
Influenza A H1n1 ◽  
The Russian Federation

Introduction. The new reassortant of the swine flu virus A(H1N1)pdm09, which emerged in 2009, overcame the species barrier and caused the 2009-2010 pandemic. One of the key points required for the influenza virus to overcome the species barrier and adapt it to humans is its specific binding to the receptors on the epithelium of the human respiratory tract.Targets and goals. Studying the dynamics of changes in receptor specificity (RS) of the HA1 subunit of the hemagglutinin of the influenza A(H1N1)pdm09 virus strains isolated during the period 2009-2016 on the territory of the Russian Federation, and an analysis of the possible impact of these changes on the incidence rates of the population of the Russian Federation of pandemic influenza in certain epidemic seasons. Material and Methods. Standard methods of collecting clinical materials, isolation of influenza viruses, their typing and genome sequencing were used. For the study of RS of influenza A virus (H1N1)pdm09, the method of solid phase sialosidenzyme analysis was used. Results. It is shown that the change in the parameter W3/6 , which characterizes the degree of a2-3 receptor specificity (a2-3-RS) of the influenza virus A(H1N1)pdm09 over a2-6-RS, coincides with the change in the incidence rates of the Russian Federation’s pandemic flu in separate epidemic seasons. There is a tendency to increase the affinity of the virus A(H1N1)pdm09 to α2-3 analogs of the sialyl-glycan receptors of the human respiratory tract epithelium - α2-3-sialoglycopolymers (α2-3-SGP), and falls to α2-6-SGP, with the virus showing the greatest affinity for sulfated sialoglycopolymers. Discussion. Screening for RS strains of influenza A (H1N1)pdm09 virus isolated on the territory of the Russian Federation in 2009-2016 revealed a decrease in the affinity of viruses for a2-6-sialosides, especially for 6’SL-SGP, which is probably due to the presence of amino acid substitutions in the 222 and 223 positions of RBS HA1 viruses. Previous studies have shown that the presence of such substitutions correlates with an increase in the virulence of the influenza A virus (H1N1)pdm09 [16, 23]. Probably, the pandemic virus has evolved towards the selection of more virulent pneumotropic variants. Conclusion. Monitoring of the receptor specificity of a pandemic influenza virus makes it possible to identify strains with altered RS to the epithelium of the human respiratory tract and an increased ability to transfer from person to person. Change in the period 2009-2016 the W3/6 parameter characterizing the degree of α2-3-RS excess of the influenza A(H1N1)pdm09 virus over α2-6-RS, coincides with the change in the incidence rates of the pandemic influenza population of the Russian Federation in certain epidemic seasons.

Pregnant women infected with pandemic influenza A(H1N1)pdm09 virus showed differential immune response correlated with disease severity

2015 ◽  
Vol 64 ◽  
pp. 52-58 ◽  
Author(s):  
N. Periolo ◽  
M. Avaro ◽  
A. Czech ◽  
M. Russo ◽  
E. Benedetti ◽  
...  
Keyword(s):  
Immune Response ◽  
Pregnant Women ◽  
Disease Severity ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Pdm09 Virus ◽  
Influenza A H1n1

scholarly journals Role of Host Immune Response and Viral Load in the Differential Outcome of Pandemic H1N1 (2009) Influenza Virus Infection in Indian Patients

PLoS ONE ◽  
2010 ◽  
Vol 5 (10) ◽  
pp. e13099 ◽  
Author(s):  
Vidya A. Arankalle ◽  
Kavita S. Lole ◽  
Ravi P. Arya ◽  
Anuradha S. Tripathy ◽  
Ashwini Y. Ramdasi ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Viral Load ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Host Immune Response ◽  
Pandemic H1n1 ◽  
Differential Outcome ◽  
Pandemic H1n1 2009

scholarly journals Double-Edged Role of Interleukin 17A in Streptococcus pneumoniae Pathogenesis During Influenza Virus Coinfection

2019 ◽  
Vol 220 (5) ◽  
pp. 902-912 ◽  
Author(s):  
Ganesh Ambigapathy ◽  
Taylor Schmit ◽  
Ram Kumar Mathur ◽  
Suba Nookala ◽  
Saad Bahri ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Puerto Rico ◽  
Streptococcus Pneumoniae ◽  
Influenza A ◽  
Invasive Disease ◽  
Wild Type ◽  
Interleukin 17A ◽  
Influenza A H1n1 ◽  
Virus Influenza

AbstractBackgroundWe sought to determine the role of host interleukin 17A (IL-17A) response against colonizing Streptococcus pneumoniae, and its transition to a pathogen during coinfection with an influenza virus, influenza A H1N1 A/Puerto Rico/8/1934 (PR8).MethodWild-type (WT) C57BL/6 mice were intranasally inoculated with S. pneumoniae serotype 6A to establish colonization and later infected with the influenza strain, PR8, resulting in invasive S. pneumoniae disease. The role of the IL-17A response in colonization and coinfection was investigated in WT, RoRγt−/− and RAG1−/− mice with antibody-mediated depletion of IL-17A (WT) and CD90 cells (RAG1−/−).ResultsRAG1−/− mice did not clear colonization and IL-17A neutralization impaired 6A clearance in WT mice. RoRγt−/− mice also had reduced clearance. S. pneumoniae–PR8 coinfection elicited a robust IL-17A response in the nasopharynx; IL-17A neutralization reduced S. pneumoniae invasive disease. RoRγt−/− mice also had reduced S. pneumoniae disease in a coinfection model. Depletion of CD90+ cells suppressed the IL-17A response and reduced S. pneumoniae invasion in RAG1−/− mice.ConclusionOur data show that although IL-17A reduces S. pneumoniae colonization, coinfection with influenza virus elicits a robust innate IL-17A response that promotes inflammation and S. pneumoniae disease in the nasopharynx.

scholarly journals Dysregulated T-Helper Type 1 (Th1):Th2 Cytokine Profile and Poor Immune Response in Pregnant Ferrets Infected With 2009 Pandemic Influenza A(H1N1) Virus

2017 ◽  
Vol 217 (3) ◽  
pp. 438-442 ◽  
Author(s):  
Sun-Woo Yoon ◽  
Sook-San Wong ◽  
Huachen Zhu ◽  
Rirong Chen ◽  
Long Li ◽  
...  
Keyword(s):  
Immune Response ◽  
Pandemic Influenza ◽  
Influenza A ◽  
H1n1 Virus ◽  
Cytokine Profile ◽  
T Helper ◽  
Th2 Cytokine ◽  
Influenza A H1n1 ◽  
Helper Type

scholarly journals Contemporary Seasonal Influenza A (H1N1) Virus Infection Primes for a More Robust Response To Split Inactivated Pandemic Influenza A (H1N1) Virus Vaccination in Ferrets

2010 ◽  
Vol 17 (12) ◽  
pp. 1998-2006 ◽  
Author(s):  
Ali H. Ellebedy ◽  
Thomas P. Fabrizio ◽  
Ghazi Kayali ◽  
Thomas H. Oguin ◽  
Scott A. Brown ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Seasonal Influenza ◽  
H1n1 Virus ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Inactivated Vaccine ◽  
H1n1 Influenza Virus ◽  
Influenza A H1n1

ABSTRACT Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.

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