Investigating Viral Interference Between Influenza A Virus and Human Respiratory Syncytial Virus in a Ferret Model of Infection

Chan, Kok Fei; Carolan, Louise; Korenkov, Daniil; Druce, Julian; McCaw, James M.; Reading, Patrick C.; Barr, Ian G.; Laurie, Karen

doi:10.1093/infdis/jiy184

Cited by 103 publications

(156 citation statements)

References 42 publications

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“…Similar to our study, others have found that respiratory viruses can induce heterologous immunity, which is highly dependent upon the order and timing of viral inoculations. Infection of ferrets with the 2009 pandemic H1N1 influenza A virus (pdm09) 3 or 7 days before RSV prevented or reduced infection by RSV (76). In contrast, while RSV infection prior to pdm09 did not prevent infection or reduce virus shedding, it did reduce the severity of influenza disease.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Influenza A Virus Disease Severity by Viral Coinfection in a Mouse Model

González

Ijezie

Balemba

et al. 2018

J Virol

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Influenza viruses and rhinoviruses are responsible for a large number of acute respiratory viral infections in human populations and are detected as copathogens within hosts. Clinical and epidemiological studies suggest that coinfection by rhinovirus and influenza virus may reduce disease severity and that they may also interfere with each other's spread within a host population. To determine how coinfection by these two unrelated respiratory viruses affects pathogenesis, we established a mouse model using a minor serogroup rhinovirus (rhinovirus strain 1B [RV1B]) and mouse-adapted influenza A virus (A/Puerto Rico/8/1934 [PR8]). Infection of mice with RV1B 2 days before PR8 reduced the severity of infection by a low or medium, but not high, dose of PR8. Disease attenuation was associated with an early inflammatory response in the lungs and enhanced clearance of PR8. However, coinfection by RV1B did not reduce PR8 viral loads early in infection or inhibit replication of PR8 within respiratory epithelia or Inflammation in coinfected mice remained focal compared to diffuse inflammation and damage in the lungs of mice infected by PR8. The timing of RV1B coinfection was a critical determinant of protection, suggesting that sufficient time is needed to induce this response. Finally, disease attenuation was not unique to RV1B: dose-dependent coinfection by a murine coronavirus (mouse hepatitis virus strain 1 [MHV-1]) also reduced the severity of PR8 infection. Unlike RV1B, coinfection with MHV-1 reduced early PR8 replication, which was associated with upregulation of beta interferon (IFN-β) expression. This model is critical for understanding the mechanisms responsible for influenza disease attenuation during coinfection by unrelated respiratory viruses. Viral infections in the respiratory tract can cause severe disease and are responsible for a majority of pediatric hospitalizations. Molecular diagnostics have revealed that approximately 20% of these patients are infected by more than one unrelated viral pathogen. To understand how viral coinfection affects disease severity, we inoculated mice with a mild viral pathogen (rhinovirus or murine coronavirus), followed 2 days later by a virulent viral pathogen (influenza A virus). This model demonstrated that rhinovirus can reduce the severity of influenza A virus, which corresponded with an early but controlled inflammatory response in the lungs and early clearance of influenza A virus. We further determined the dose and timing parameters that were important for effective disease attenuation and showed that influenza disease is also reduced by coinfection with a murine coronavirus. These findings demonstrate that coinfecting viruses can alter immune responses and pathogenesis in the respiratory tract.

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Section: Discussionmentioning

confidence: 99%

Attenuation of Influenza A Virus Disease Severity by Viral Coinfection in a Mouse Model

González

Ijezie

Balemba

et al. 2018

J Virol

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“…A key result was that varied infection kinetics and outcomes could manifest from changing the virus dose or the intrinsic virus growth rate. Although RSV dose may not affect the interaction during IAV‐RSV coinfection, the finding is relevant for RV‐IAV coinfection . However, interference in the infection of epithelial cells is not the proposed mechanism for these viruses .…”

Section: Viral–viral Coinfection Kineticsmentioning

confidence: 90%

“…In a similar interaction, IAV infection attenuates RSV by inhibiting protein synthesis and does so with little impact on IAV titers . In contrast, pre‐infection with RSV or RV does not impact influenza virus replication but can reduce disease severity . For RV, this is due to enhanced clearance of influenza virions .…”

Section: Viral–viral Coinfection Kineticsmentioning

confidence: 99%

“…Given that different virus pairings result in different outcomes (ie, infection enhancement or reduction), use of anti‐influenza therapy could result in beneficial or adverse consequences . In the case of IAV‐RSV coinfection, where influenza viruses reduce RSV growth, antiviral therapy that limits IAV infection could inadvertently result in a resurgence of RSV replication. It's unclear if the off‐target effects of NAIs would be sufficient to facilitate or limit spread of the second virus.…”

Section: Antiviral Therapy: the Case For Immunomodulatory Drugsmentioning

confidence: 99%

“…Influenza viruses that cause severe disease support higher incidence of bacterial coinfection, yet only a proportion of infections result in a coinfection . Furthermore, other respiratory viruses may also coinfect and enhance influenza‐related disease . Factors that impact influenza severity and, thus, coinfection risk are not well understood.…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

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Host‐pathogen kinetics during influenza infection and coinfection: insights from predictive modeling

Smith

2018

Immunological Reviews

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SummaryInfluenza virus infections are a leading cause of morbidity and mortality worldwide. This is due in part to the continual emergence of new viral variants and to synergistic interactions with other viruses and bacteria. There is a lack of understanding about how host responses work to control the infection and how other pathogens capitalize on the altered immune state. The complexity of multi‐pathogen infections makes dissecting contributing mechanisms, which may be non‐linear and occur on different time scales, challenging. Fortunately, mathematical models have been able to uncover infection control mechanisms, establish regulatory feedbacks, connect mechanisms across time scales, and determine the processes that dictate different disease outcomes. These models have tested existing hypotheses and generated new hypotheses, some of which have been subsequently tested and validated in the laboratory. They have been particularly a key in studying influenza‐bacteria coinfections and will be undoubtedly be useful in examining the interplay between influenza virus and other viruses. Here, I review recent advances in modeling influenza‐related infections, the novel biological insight that has been gained through modeling, the importance of model‐driven experimental design, and future directions of the field.

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Clinical features and viral etiology of acute respiratory infection in an outpatient fever clinic during COVID‐19 pandemic in a tertiary hospital in Nanjing, China

Geng

Hao

et al. 2022

Clinical Laboratory Analysis

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Background Clinical feature and viral etiology for acute respiratory infection (ARI) in the community was unknown during coronavirus disease 2019 (COVID‐19) pandemic. Objective In a retrospective study, we aimed to characterize the clinical feature and etiology for the ARI patients admitted to the outpatient fever clinic in Nanjing Drum Tower Hospital between November 2020 and March 2021. Methods Fifteen common respiratory pathogens were tested using pharyngeal swabs by multiplex reverse transcriptase‐polymerase chain reaction assays. Results Of the 242 patients, 56 (23%) were tested positive for at least one viral agent. The predominant viruses included human rhinovirus (HRV) (5.4%), parainfluenza virus type III (PIV‐III) (5.0%), and human coronavirus‐NL63 (HCoV‐NL63) (3.7%). Cough, sputum, nasal obstruction, and rhinorrhea were the most prevalent symptoms in patients with viral infection. Elderly and the patients with underlying diseases were susceptible to pneumonia accompanied with sputum and chest oppression. Three (5.4%) patients in virus infection group, whereas 31 (16.7%) in non‐viral infection group (p = 0.033), were empirically prescribed with antiviral agents. Among 149 patients who received antibiotic therapy, 30 (20.1%) patients were later identified with viral infection. Conclusion Our study indicated the importance of accurate diagnosis of ARI, especially during the COVID‐19 pandemic, which might facilitate appropriate clinical treatment.

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Investigating Viral Interference Between Influenza A Virus and Human Respiratory Syncytial Virus in a Ferret Model of Infection

Cited by 103 publications

References 42 publications

Attenuation of Influenza A Virus Disease Severity by Viral Coinfection in a Mouse Model

Attenuation of Influenza A Virus Disease Severity by Viral Coinfection in a Mouse Model

Host‐pathogen kinetics during influenza infection and coinfection: insights from predictive modeling

Clinical features and viral etiology of acute respiratory infection in an outpatient fever clinic during COVID‐19 pandemic in a tertiary hospital in Nanjing, China

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