tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2023 Apr 25;120(17):e2218623120.
doi: 10.1073/pnas.2218623120. Epub 2023 Apr 17.
Tight junction protein occludin is an internalization factor for SARS-CoV-2 infection and mediates virus cell-to-cell transmission
Jialin Zhang[SUP] 1 2 [/SUP], Wenyu Yang[SUP] 1 2 [/SUP], Sawrab Roy[SUP] 1 2 [/SUP], Heidi Liu[SUP] 1 2 [/SUP], R Michael Roberts[SUP] 3 4 [/SUP], Liping Wang[SUP] 1 2 [/SUP], Lei Shi[SUP] 1 2 [/SUP], Wenjun Ma[SUP] 1 2 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads efficiently by spike-mediated, direct cell-to-cell transmission. However, the underlying mechanism is poorly understood. Herein, we demonstrate that the tight junction protein occludin (OCLN) is critical to this process. SARS-CoV-2 infection alters OCLN distribution and expression and causes syncytium formation that leads to viral spread. OCLN knockdown fails to alter SARS-CoV-2 binding but significantly lowers internalization, syncytium formation, and transmission. OCLN overexpression also has no effect on virus binding but enhances virus internalization, cell-to-cell transmission, and replication. OCLN directly interacts with the SARS-CoV-2 spike, and the endosomal entry pathway is involved in OCLN-mediated cell-to-cell fusion rather than in the cell surface entry pathway. All SARS-CoV-2 strains tested (prototypic, alpha, beta, gamma, delta, kappa, and omicron) are dependent on OCLN for cell-to-cell transmission, although the extent of syncytium formation differs between strains. We conclude that SARS-CoV-2 utilizes OCLN as an internalization factor for cell-to-cell transmission.
Keywords: SARS-CoV-2; SARS-CoV-2 variants; cell-to-cell transmission; internalization; occludin.
. 2023 Apr 25;120(17):e2218623120.
doi: 10.1073/pnas.2218623120. Epub 2023 Apr 17.
Tight junction protein occludin is an internalization factor for SARS-CoV-2 infection and mediates virus cell-to-cell transmission
Jialin Zhang[SUP] 1 2 [/SUP], Wenyu Yang[SUP] 1 2 [/SUP], Sawrab Roy[SUP] 1 2 [/SUP], Heidi Liu[SUP] 1 2 [/SUP], R Michael Roberts[SUP] 3 4 [/SUP], Liping Wang[SUP] 1 2 [/SUP], Lei Shi[SUP] 1 2 [/SUP], Wenjun Ma[SUP] 1 2 [/SUP]
Affiliations
- PMID: 37068248
- DOI: 10.1073/pnas.2218623120
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads efficiently by spike-mediated, direct cell-to-cell transmission. However, the underlying mechanism is poorly understood. Herein, we demonstrate that the tight junction protein occludin (OCLN) is critical to this process. SARS-CoV-2 infection alters OCLN distribution and expression and causes syncytium formation that leads to viral spread. OCLN knockdown fails to alter SARS-CoV-2 binding but significantly lowers internalization, syncytium formation, and transmission. OCLN overexpression also has no effect on virus binding but enhances virus internalization, cell-to-cell transmission, and replication. OCLN directly interacts with the SARS-CoV-2 spike, and the endosomal entry pathway is involved in OCLN-mediated cell-to-cell fusion rather than in the cell surface entry pathway. All SARS-CoV-2 strains tested (prototypic, alpha, beta, gamma, delta, kappa, and omicron) are dependent on OCLN for cell-to-cell transmission, although the extent of syncytium formation differs between strains. We conclude that SARS-CoV-2 utilizes OCLN as an internalization factor for cell-to-cell transmission.
Keywords: SARS-CoV-2; SARS-CoV-2 variants; cell-to-cell transmission; internalization; occludin.