SARS CoV-2 Nucleoprotein Enhances the Infectivity of Lentiviral Spike Particles.

Frontiers in Cellular and Infection Microbiology
Tarun MishraAjit Chande


The establishment of SARS CoV-2 spike-pseudotyped lentiviral (LV) systems has enabled the rapid identification of entry inhibitors and neutralizing agents, alongside allowing for the study of this emerging pathogen in BSL-2 level facilities. While such frameworks recapitulate the cellular entry process in ACE2+ cells, they are largely unable to factor in supplemental contributions by other SARS CoV-2 genes. To address this, we performed an unbiased ORF screen and identified the nucleoprotein (N) as a potent enhancer of spike-pseudotyped LV particle infectivity. We further demonstrate that the spike protein is better enriched in virions when the particles are produced in the presence of N protein. This enrichment of spike renders LV particles more infectious as well as less vulnerable to the neutralizing effects of a human IgG-Fc fused ACE2 microbody. Importantly, this improvement in infectivity is observed with both wild-type spike protein as well as the D614G mutant. Our results hold important implications for the design and interpretation of similar LV pseudotyping-based studies.


Nov 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Ajit ChandeMassimo Pizzato
Apr 26, 2020·Nature Communications·Changhai LeiShi Hu
May 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jian ShangFang Li
Aug 14, 2020·Journal of Virology·Marc C JohnsonDetlef G Ritter
Aug 25, 2020·Informatics in Medicine Unlocked·Babak KhorsandMahmoud Naghibzadeh
Sep 11, 2020·Nature Structural & Molecular Biology·Katharina SchubertNenad Ban
Sep 28, 2020·Cell Reports·Hongjie XiaPei-Yong Shi
Nov 21, 2020·The Journal of Biological Chemistry·Caroline B PlesciaRobert V Stahelin
Nov 28, 2020·Nature Communications·Lizhou ZhangHyeryun Choe
Dec 29, 2020·Proceedings of the National Academy of Sciences of the United States of America·Thomas G FlowerJames H Hurley
Jan 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Christopher P LapointeJoseph D Puglisi

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