Distinct Inductions of and Responses to Type I and Type III Interferons PromoteInfections in Two SARS-CoV-2 Isolates

Hsin, F.; Chao, T.-L.; Chan, Y.-R.; Kao, H.-C.; Liu, W.-D.; Wang, J.-T.; Pang, Y.-H.; Lin, C.-H.; Tsai, Y.-M.; Lin, J.-Y.; Chang, S.-Y.; Liu, H. M.

doi:10.1101/2020.04.30.071357

bioRxiv · 10.1101/2020.04.30.071357

Distinct Inductions of and Responses to Type I and Type III Interferons PromoteInfections in Two SARS-CoV-2 Isolates

Hsin, F.·Chao, T.-L.·Chan, Y.-R.·Kao, H.-C.·Liu, W.-D.·Wang, J.-T.·Pang, Y.-H.·Lin, C.-H.·Tsai, Y.-M.·Lin, J.-Y.·Chang, S.-Y.·Liu, H. M.

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Abstract

The recent emerging coronavirus, SARS-CoV-2, has been rapidly and widely spread and causing an ongoing viral pneumonia outbreak worldwide. It has been observed that SARS-CoV-2 patients show a rather long and asymptomatic incubation time. We characterized the abilities to induce and to response to IFN{beta}/IFN{lambda}1 of two or our clinical isolates, SARS-CoV-2/NTU01/TWN/human/2020 and SARS-CoV-2/NTU02/TWN/human/2020, which exhibit only two amino acid differences over the [~]30kb viral genome. We found that both isolates may infect Huh7, A549 and Calu-3 cells, yet the RIG-I-like receptor-dependent antiviral signaling was poorly induced in these cells in the early infections. Unexpectedly, we found that the intracellular vRNA levels of these isolates were sustained upon to type I/III IFN treatments, and this phenotype was more pronounced in the Taiwan/NTU01/2020 isolate. The type I/III IFN responses are antiviral but partially proviral in the case of SARS-CoV-2 infections. Poor induction and response to innate immunity may contribute to destitute neutralization index of the antibody produced, and indeed we found that the patient serum could not efficiently neutralize SARS-CoV-2 virions. With better understandings of the interplay between SARS-CoV-2 and the host antiviral innate immunity, our report may provide new insights for the regimen of therapies for SARS-CoV-2 infected patients.

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Hsin, F., Chao, T.-L., Chan, Y.-R., Kao, H.-C., Liu, W.-D., Wang, J.-T., Pang, Y.-H., Lin, C.-H., Tsai, Y.-M., Lin, J.-Y., Chang, S.-Y., Liu, H. M.. 2020-05-01. Distinct Inductions of and Responses to Type I and Type III Interferons PromoteInfections in Two SARS-CoV-2 Isolates. https://doi.org/10.1101/2020.04.30.071357

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