PT  - JOURNAL ARTICLE
AU  - Lisa Bauer
AU  - Bas Lendemeijer
AU  - Lonneke Leijten
AU  - Carmen W. E. Embregts
AU  - Barry Rockx
AU  - Steven A. Kushner
AU  - Femke M.S. de Vrij
AU  - Debby van Riel
TI  - Replication kinetic, cell tropism and associated immune responses in SARS-CoV-2 and H5N1 virus infected human iPSC derived neural models
AID  - 10.1101/2021.03.15.435472
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.15.435472
4099  - http://biorxiv.org/content/early/2021/03/16/2021.03.15.435472.short
4100  - http://biorxiv.org/content/early/2021/03/16/2021.03.15.435472.full
AB  - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a wide variety of neurological complications. Even though SARS-CoV-2 is rarely detected in the central nervous system (CNS) or cerebrospinal fluid, evidence is accumulating that SARS-CoV-2 might enter the CNS via the olfactory nerve. However, what happens after SARS-CoV-2 enters the CNS is poorly understood. Therefore, we investigated the replication kinetics, cell tropism, and associated immune responses of SARS-CoV-2 infection in different types of neural cultures derived from human induced pluripotent stem cells (hiPSCs). SARS-CoV-2 was compared to the neurotropic and highly pathogenic H5N1 influenza A virus. SARS-CoV-2 infected a minority of individual mature neurons, without subsequent virus replication and spread, despite ACE2, TMPRSS2 and NPR1 expression in all cultures. However, this sparse infection did result in the production of type-III-interferons and IL-8. In contrast, H5N1 virus replicated and spread very efficiently in all cell types in all cultures. Taken together, our findings support the hypothesis that neurological complications might result from local immune responses triggered by virus invasion, rather than abundant SARS-CoV-2 replication in the CNS.Competing Interest StatementThe authors have declared no competing interest.