Abstract
Influenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance has shown that RSV infection generally precedes influenza. However, in the last four winter seasons (2016–2020) an overlap of the morbidity peaks of both viruses was observed in Israel, and was paralleled by significantly lower RSV infection rates. To investigate whether the influenza A virus inhibits RSV, human cervical carcinoma (HEp2) cells or mice were co-infected with influenza A and RSV. Influenza A inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza A identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with the tetratricopeptide (IFITs) family. Interestingly, in the second wave, influenza A viruses were no longer detectable in mouse lungs. In addition, knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza A infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding the immune system involvement in the interaction between influenza A and RSV viruses will contribute to the development of future treatment strategies against these viruses.
Highlights
Respiratory syncytial virus (RSV) and influenza viruses are two respiratory viruses associated with significant morbidity and mortality worldwide [1]
Samples from non-hospitalized patients with influenza-like illness (ILI) were collected as part of the seasonal influenza surveillance network, which operates in collaboration with the Israeli Center for Disease Control (ICDC) in dozens of clinics in Israel (Helsinki Number 1967-15-SMC)
In the winter seasons 2013–2016, RSV infection was detected in October, and peaked in December, while influenza infections peaked in the middle of January (Figure 1A) and February (Figure 1B)
Summary
Respiratory syncytial virus (RSV) and influenza viruses are two respiratory viruses associated with significant morbidity and mortality worldwide [1]. In Israel, RSV is usually detected in October, with a clear peak in December, whereas the influenza virus arrives in November and peaks in January [8]. In the last four seasons, influenza infection overlapped with that of RSV in Israel, which resulted in decreased RSV-related morbidity. The activity of both innate and adaptive immune systems against both viruses is very well documented [2,10]. Innate immunity against these viruses includes, among others, the interferon-stimulating
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