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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell 2021 ; 184 (8): 2229-2238.e13 Nephropedia Template TP
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A trans-complementation system for SARS-CoV-2 recapitulates authentic viral replication without virulence #MMPMID33691138
Zhang X; Liu Y; Liu J; Bailey AL; Plante KS; Plante JA; Zou J; Xia H; Bopp NE; Aguilar PV; Ren P; Menachery VD; Diamond MS; Weaver SC; Xie X; Shi PY
Cell 2021[Apr]; 184 (8): 2229-2238.e13 PMID33691138show ga
The biosafety level 3 (BSL-3) requirement to culture severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a bottleneck for research. Here, we report a trans-complementation system that produces single-round infectious SARS-CoV-2 that recapitulates authentic viral replication. We demonstrate that the single-round infectious SARS-CoV-2 can be used at BSL-2 laboratories for high-throughput neutralization and antiviral testing. The trans-complementation system consists of two components: a genomic viral RNA containing ORF3 and envelope gene deletions, as well as mutated transcriptional regulator sequences, and a producer cell line expressing the two deleted genes. Trans-complementation of the two components generates virions that can infect naive cells for only one round but does not produce wild-type SARS-CoV-2. Hamsters and K18-hACE2 transgenic mice inoculated with the complementation-derived virions exhibited no detectable disease, even after intracranial inoculation with the highest possible dose. Thus, the trans-complementation platform can be safely used at BSL-2 laboratories for research and countermeasure development.