Generation of chimeric respiratory viruses with altered tropism by coinfection of influenza A virus and respiratory syncytial virus

SummaryInteractions between co-circulating respiratory viruses are recognized for their impact on viral transmission and clinical outcomes. However, the consequences of these virus-virus interactions at the cellular level are unclear. We coinfected human lung cells with influenza A virus (IAV) and respiratory syncytial virus (RSV). Super-resolution microscopy combined with live-cell imaging and scanning electron microscopy identified extracellular and membrane-associated filamentous structures, likely composed of elements of both IAV and RSV virions. Cryo-electron tomography confirmed the presence of chimeric virus particles exhibiting glycoproteins and ribonucleoproteins of both parental viruses. Functional assays revealed chimeric particles facilitate IAV infection in cells depleted of IAV receptors, demonstrating expanded tropism. Our observations define a previously unknown interaction that is likely to affect virus pathogenesis and have profound implications for infection biology.

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Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽

10.3390/v13020234 ◽

2021 ◽

Vol 13 (2) ◽

pp. 234

Author(s):

Sarah Al-Beltagi ◽

Cristian Alexandru Preda ◽

Leah V. Goulding ◽

Joe James ◽

Juan Pu ◽

...

Keyword(s):

Influenza Virus ◽

Respiratory Syncytial Virus ◽

Influenza A Virus ◽

Broad Spectrum ◽

Influenza A ◽

Respiratory Viruses ◽

Influenza Viruses ◽

Virus Challenge ◽

2009 H1n1 ◽

Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

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Characterising Interactions between Influenza A Virus and Respiratory Syncytial Virus during In Vitro Coinfection

Proceedings ◽

10.3390/proceedings2020050048 ◽

2020 ◽

Vol 50 (1) ◽

pp. 48

Author(s):

Joanne Haney ◽

Kieran Dee ◽

Colin Loney ◽

Swetha Vijayakrishnan ◽

Pablo R. Murcia

Keyword(s):

Respiratory Syncytial Virus ◽

Influenza A Virus ◽

Influenza A ◽

Lung Epithelial Cells ◽

Respiratory Pathogens ◽

Biological Interactions ◽

Infection Dynamics ◽

Syncytial Virus ◽

Virus Interactions

Influenza A virus (IAV) and respiratory syncytial virus (RSV) are important respiratory pathogens that share common epidemiological features and cellular tropism within the respiratory tract. This gives rise to the potential for biological interactions between IAV and RSV during coinfection of hosts. Virus–virus interactions are increasingly recognised for their contribution to viral dynamics during infection, however, the molecular processes underpinning these interactions are unknown. Here, we developed an in vitro coinfection system to characterise the infection dynamics of IAV (A/Puerto Rico/8/34, H1N1) and RSV (A2) in single virus infection or coinfection in lung epithelial cells, with the aim to identify biological processes that drive virus–virus interactions during coinfection. We compared viral replication kinetics at different multiplicities of infection and observed that RSV replication was inhibited during coinfection with IAV, whilst IAV replication was facilitated by coinfection. To further characterise IAV/RSV interactions, we determined the relative proportions of single virus infected or coinfected cells during early and late timepoints post-infection and observed differences in expression of viral proteins between single and coinfected states. Additionally, cell viability was measured determine differences in viral-induced cytopathic effect. Compared with RSV infection, cell death is induced at earlier timepoints post IAV infection and coinfection, indicating that different cellular processes are initiated in response to infection. These studies highlight that both competitive and facilitative ecological interactions occur between IAV and RSV during coinfection and shed light on sources of potential interactions at the cellular and molecular level.

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Protective Efficacy and Immunogenicity of a Combinatory DNA Vaccine against Influenza A Virus and the Respiratory Syncytial Virus

PLoS ONE ◽

10.1371/journal.pone.0072217 ◽

2013 ◽

Vol 8 (8) ◽

pp. e72217 ◽

Cited By ~ 16

Author(s):

Viktoria Stab ◽

Sandra Nitsche ◽

Thomas Niezold ◽

Michael Storcksdieck genannt Bonsmann ◽

Andrea Wiechers ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Influenza A Virus ◽

Dna Vaccine ◽

Influenza A ◽

Protective Efficacy ◽

Syncytial Virus

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Circulation of Respiratory Viruses in Hospitalized Adults before and during the COVID-19 Pandemic in Brescia, Italy: A Retrospective Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18189525 ◽

2021 ◽

Vol 18 (18) ◽

pp. 9525

Author(s):

Maria Antonia De Francesco ◽

Caterina Pollara ◽

Franco Gargiulo ◽

Mauro Giacomelli ◽

Arnaldo Caruso

Keyword(s):

Respiratory Syncytial Virus ◽

Influenza A ◽

Statistical Significance ◽

Respiratory Viruses ◽

Influenza Viruses ◽

Contact Tracing ◽

Nucleic Acid Detection ◽

Respiratory Pathogens ◽

Syncytial Virus ◽

Human Coronaviruses

Different preventive public health measures were adopted globally to limit the spread of SARS-CoV-2, such as hand hygiene and the use of masks, travel restrictions, social distance actions such as the closure of schools and workplaces, case and contact tracing, quarantine and lockdown. These measures, in particular physical distancing and the use of masks, might have contributed to containing the spread of other respiratory viruses that occurs principally by contact and droplet routes. The aim of this study was to evaluate the prevalence of different respiratory viruses (influenza viruses A and B, respiratory syncytial virus, parainfluenza viruses 1, 2, 3 and 4, rhinovirus, adenovirus, metapneumovirus and human coronaviruses) after one year of the pandemic. Furthermore, another aim was to evaluate the possible impact of these non-pharmaceutical measures on the circulation of seasonal respiratory viruses. This single center study was conducted between January 2017–February 2020 (pre-pandemic period) and March 2020–May 2021 (pandemic period). All adults >18 years with respiratory symptoms and tested for respiratory pathogens were included in the study. Nucleic acid detection of all respiratory viruses was performed by multiplex real time PCR. Our results show that the test positivity for influenza A and B, metapneumovirus, parainfluenza virus, respiratory syncytial virus and human coronaviruses decreased with statistical significance during the pandemic. Contrary to this, for adenovirus the decrease was not statistically significant. Conversely, a statistically significant increase was detected for rhinovirus. Coinfections between different respiratory viruses were observed during the pre-pandemic period, while the only coinfection detected during pandemic was between SARS-CoV-2 and rhinovirus. To understand how the preventive strategies against SARS-CoV-2 might alter the transmission dynamics and epidemic patterns of respiratory viruses is fundamental to guide future preventive recommendations.

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Exacerbation of Influenza A Virus Disease Severity by Respiratory Syncytial Virus Co-Infection in a Mouse Model

Viruses ◽

10.3390/v13081630 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1630 ◽

Cited By ~ 1

Author(s):

Junu A. George ◽

Shaikha H. AlShamsi ◽

Maryam H. Alhammadi ◽

Ahmed R. Alsuwaidi

Keyword(s):

T Cells ◽

Respiratory Syncytial Virus ◽

Influenza A Virus ◽

Influenza A ◽

Immune Cell ◽

Virus Disease ◽

Viral Loads ◽

Syncytial Virus

Influenza A virus (IAV) and respiratory syncytial virus (RSV) are leading causes of childhood infections. RSV and influenza are competitive in vitro. In this study, the in vivo effects of RSV and IAV co-infection were investigated. Mice were intranasally inoculated with RSV, with IAV, or with both viruses (RSV+IAV and IAV+RSV) administered sequentially, 24 h apart. On days 3 and 7 post-infection, lung tissues were processed for viral loads and immune cell populations. Lung functions were also evaluated. Mortality was observed only in the IAV+RSV group (50% of mice did not survive beyond 7 days). On day 3, the viral loads in single-infected and co-infected mice were not significantly different. However, on day 7, the IAV titer was much higher in the IAV+RSV group, and the RSV viral load was reduced. CD4 T cells were reduced in all groups on day 7 except in single-infected mice. CD8 T cells were higher in all experimental groups except the RSV-alone group. Increased airway resistance and reduced thoracic compliance were demonstrated in both co-infected groups. This model indicates that, among all the infection types we studied, infection with IAV followed by RSV is associated with the highest IAV viral loads and the most morbidity and mortality.

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A novel p38 mitogen activated protein kinase (MAPK) specific inhibitor suppresses respiratory syncytial virus and influenza A virus replication by inhibiting virus-induced p38 MAPK activation

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2016.06.111 ◽

2016 ◽

Vol 477 (3) ◽

pp. 311-316 ◽

Cited By ~ 16

Author(s):

Myung-Soo Choi ◽

Jinyuk Heo ◽

Chae-Min Yi ◽

Junsu Ban ◽

Noh-Jin Lee ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Protein Kinase ◽

Influenza A Virus ◽

Virus Replication ◽

Influenza A ◽

Specific Inhibitor ◽

Mitogen Activated Protein Kinase ◽

Mapk Activation ◽

Mitogen Activated Protein ◽

Syncytial Virus

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Respiratory Viral Pathogens in Children Evaluated at Military Treatment Facilities in Oahu, Hawaii From 2014 to 2018: Seasonality and Climatic Factors

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piaa131 ◽

2020 ◽

Author(s):

Agnes S Montgomery ◽

Michael B Lustik ◽

Milissa U Jones ◽

Timothy S Horseman

Keyword(s):

Respiratory Syncytial Virus ◽

Influenza A ◽

Climatic Factors ◽

Medical Center ◽

Respiratory Viruses ◽

Preventive Strategies ◽

Viral Pathogens ◽

Treatment Facilities ◽

Syncytial Virus ◽

Military Treatment Facilities

Abstract Five-year retrospective analysis of respiratory viruses in children less than 18 years old at Tripler Army Medical Center and outlying clinics in Oahu. Respiratory syncytial virus and influenza A showed pronounced seasonality with peaks from September to December and December to March, respectively. Results provide a better understanding of the timing of viral preventive strategies in Oahu.

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