tetano
Editor, Senior Moderator
EMBO J
. 2022 Sep 26;e111653.
doi: 10.15252/embj.2022111653. Online ahead of print.
Cyclin D3 restricts SARS-CoV-2 Envelope incorporation into virions and interferes with viral spread
Ravi K Gupta[SUP] 1 2 3 [/SUP], Petra Mlcochova[SUP] 1 2 [/SUP]
Affiliations
Abstract
The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents a great threat to human health. The interplay between the virus and host plays a crucial role in successful virus replication and transmission. Understanding host virus interactions is essential for development of new COVID-19 treatment strategies. Here we show that SARS-CoV-2 infection triggers redistribution of cyclin D1 and cyclin D3 from the nucleus to the cytoplasm, followed by their proteasomal degradation. No changes to other cyclins or cyclin dependent kinases were observed. Further, cyclin D depletion was independent from SARS-CoV-2-mediated cell cycle arrest in early S phase or S/G2/M phase. Cyclin D3 knockdown by small interfering RNA specifically enhanced progeny virus titres in supernatants. Finally, cyclin D3 co-immunoprecipitated with SARS-CoV-2 Envelope (E) and Membrane (M) proteins. We propose that cyclin D3 impairs efficient incorporation of Envelope protein into virions during assembly and is depleted during SARS-CoV-2 infection to restore efficient assembly and release of newly produced virions.
Keywords: Fucci; SARS-CoV-2; assembly; cell cycle; cyclin D3.
. 2022 Sep 26;e111653.
doi: 10.15252/embj.2022111653. Online ahead of print.
Cyclin D3 restricts SARS-CoV-2 Envelope incorporation into virions and interferes with viral spread
Ravi K Gupta[SUP] 1 2 3 [/SUP], Petra Mlcochova[SUP] 1 2 [/SUP]
Affiliations
- PMID: 36161661
- DOI: 10.15252/embj.2022111653
Abstract
The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents a great threat to human health. The interplay between the virus and host plays a crucial role in successful virus replication and transmission. Understanding host virus interactions is essential for development of new COVID-19 treatment strategies. Here we show that SARS-CoV-2 infection triggers redistribution of cyclin D1 and cyclin D3 from the nucleus to the cytoplasm, followed by their proteasomal degradation. No changes to other cyclins or cyclin dependent kinases were observed. Further, cyclin D depletion was independent from SARS-CoV-2-mediated cell cycle arrest in early S phase or S/G2/M phase. Cyclin D3 knockdown by small interfering RNA specifically enhanced progeny virus titres in supernatants. Finally, cyclin D3 co-immunoprecipitated with SARS-CoV-2 Envelope (E) and Membrane (M) proteins. We propose that cyclin D3 impairs efficient incorporation of Envelope protein into virions during assembly and is depleted during SARS-CoV-2 infection to restore efficient assembly and release of newly produced virions.
Keywords: Fucci; SARS-CoV-2; assembly; cell cycle; cyclin D3.