While inflammation is part of kicking out the virus, it can get out of control, especially with more "foreign" viruses, like those that are still zoonotic and not as co-evolved with humans. Excessive inflammation can lead to tissue remodelling and damage.
In their paper in the Journal of General Virology, the authors compared the results of growing viruses in 2 different cell systems, which was need to account for differences in tropism by the different viruses. Key findings include:
- The lower airway cell-line, CaLu-3 was used for MERS-CoV and SARS-CoV because they produce good titres
- IL-1β, IL-6, IL-8, TNF-α, IFN-β & IP-10 mRNA levels were increased by MERS-CoV and SARS-CoV compared to uninfected cells
- Proinflammatory cytokines shown in bold above were induced more by MERS-CoV infection than by SARS-CoV
- Innate antiviral cytokines TNF-α, IFN-β & IP-10 were induced more by SARS-CoV infection
- MCP-1 (a chemokine) and TGF-β (anti-inflammatory cytokine) remained unimpressed by infection
- At 48-hours, MERS-CoV infection induced less IL-8 or IFN-β protein than did SARS-CoV
- Embryonal lung fibroblasts (HFL) to grow MERS-CoV and compare it to HCoV-229E (which does not grow well in CaLu-3 cells), an infrequently identified but well characterised "common cold" CoV.
- The CaLu-3 results suggested MERS-CoV generates an attenuated innate immune response the response which induces inflammation. SO HCoV-229E was added as it produces a strong innate response through IFN-β
- IL-1β, IL-6, IL-8, TNF-α, IFN-β & IP-10 mRNA levels were increased by MERS-CoV and HCoV-229E
- HCoV-229E was a stronger inducer than MERS-CoV of all but TNF-α, which triggered more by MERS-CoV
- MCP-1 and TGF-β again remained unchanged
The authors conclude a delayed innate immune response by MERS-CoV infection compared to SARS-CoV.
This study contrasted with that by Kindler and colleagues which I reviewed earlier. The reason may be because Kindler only sampled for immune analyses up to 12-hours, rather than the 30-hours used by Lau. This would certainly lend weight to claims of a "delayed" induction by MERS-CoV infection since in this study no IFN-β was produced either virus at 12-hour, the first rise in mRNA was apparent at 24-hour post-infection (Lau's protein data suggest there may have been a tiny amount of IFN-β translation at 12-hours, but Kindler did not measure protein).