SARS-CoV-2 spreads through cell-to-cell transmission

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. Herein, we provide evidence that SARS-CoV-2 spreads through cell–cell contact in cultures, mediated by the spike glycoprotein. SARS-CoV-2 spike is more efficient in facilitating cell-to-cell transmission than is SARS-CoV spike, which reflects, in part, their differential cell–cell fusion activity. Interestingly, treatment of cocultured cells with endosomal entry inhibitors impairs cell-to-cell transmission, implicating endosomal membrane fusion as an underlying mechanism. Compared with cell-free infection, cell-to-cell transmission of SARS-CoV-2 is refractory to inhibition by neutralizing antibody or convalescent sera of COVID-19 patients. While angiotensin-converting enzyme 2 enhances cell-to-cell transmission, we find that it is not absolutely required. Notably, despite differences in cell-free infectivity, the authentic variants of concern (VOCs) B.1.1.7 (alpha) and B.1.351 (beta) have similar cell-to-cell transmission capability. Moreover, B.1.351 is more resistant to neutralization by vaccinee sera in cell-free infection, whereas B.1.1.7 is more resistant to inhibition by vaccinee sera in cell-to-cell transmission. Overall, our study reveals critical features of SARS-CoV-2 spike-mediated cell-to-cell transmission, with important implications for a better understanding of SARS-CoV-2 spread and pathogenesis.

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SARS-CoV-2 Spreads through Cell-to-Cell Transmission

10.1101/2021.06.01.446579 ◽

2021 ◽

Author(s):

Cong Zeng ◽

John P. Evans ◽

Tiffany King ◽

Yi-Min Zheng ◽

Eugene M. Oltz ◽

...

Keyword(s):

Neutralizing Antibody ◽

Underlying Mechanism ◽

Cell Contact ◽

Fusion Activity ◽

Endosomal Membrane ◽

Entry Inhibitors ◽

Differential Cell ◽

Cell Transmission ◽

Transmission Capability ◽

Cell Cell

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. Herein we provide evidence that SARS-CoV-2 spreads through cell-cell contact in cultures, mediated by the spike glycoprotein. SARS-CoV-2 spike is more efficient in facilitating cell-to-cell transmission than SARS-CoV spike, which reflects, in part, their differential cell-cell fusion activity. Interestingly, treatment of cocultured cells with endosomal entry inhibitors impairs cell-to-cell transmission, implicating endosomal membrane fusion as an underlying mechanism. Compared with cell-free infection, cell-to-cell transmission of SARS-CoV-2 is refractory to inhibition by neutralizing antibody or convalescent sera of COVID-19 patients. While ACE2 enhances cell-to-cell transmission, we find that it is not absolutely required. Notably, despite differences in cell-free infectivity, the variants of concern (VOC) B.1.1.7 and B.1.351 have similar cell-to-cell transmission capability. Moreover, B.1.351 is more resistant to neutralization by vaccinee sera in cell-free infection, whereas B.1.1.7 is more resistant to inhibition by vaccine sera in cell-to-cell transmission. Overall, our study reveals critical features of SARS-CoV-2 spike-mediated cell-to-cell transmission, with important implications for a better understanding of SARS-CoV-2 spread and pathogenesis.

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Periodontal ligament stem cells regulate apoptosis of neutrophils

Open Medicine ◽

10.1515/med-2017-0004 ◽

2017 ◽

Vol 12 (1) ◽

pp. 19-23 ◽

Cited By ~ 9

Author(s):

Qing Wang ◽

Gang Ding ◽

Xin Xu

Keyword(s):

Stem Cells ◽

Periodontal Ligament ◽

Neutralizing Antibody ◽

Cell Contact ◽

Neutrophil Apoptosis ◽

Periodontal Ligament Stem Cells ◽

Cell Based Therapy ◽

Transwell Culture ◽

Underlying Mechanisms ◽

Cell Cell

AbstractPeriodontal ligament stem cells (PDLSCs) are promising cell resource for the cell-based therapy for periodontitis and regeneration of bio-root. In this study, we investigated the effect of PDLSCs on neutrophil, a critical constituent of innate immunity, and the underlying mechanisms. The effect of PDLSCs on the proliferation and apoptosis of resting neutrophils and IL-8 activated neutrophils was tested under cell-cell contact culture and Transwell culture, with or without anti-IL-6 neutralizing antibody. We found that PDLSCs could promote the proliferation and reduce the apoptosis of neutrophils whether under cell-cell contact or Transwell culture. Anti-IL-6 antibody reduced PDLSCs-mediated inhibition of neutrophil apoptosis. IL-6 at the concentration of 10ng/ml and 20ng/ml could inhibit neutrophil apoptosis statistically. Collectively, PDLSCs could reduce the apoptosis of neutrophils via IL-6.

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Virus Cell-to-Cell Transmission

Journal of Virology ◽

10.1128/jvi.00443-10 ◽

2010 ◽

Vol 84 (17) ◽

pp. 8360-8368 ◽

Cited By ~ 185

Author(s):

Walther Mothes ◽

Nathan M. Sherer ◽

Jing Jin ◽

Peng Zhong

Keyword(s):

Cell Adhesion Molecules ◽

Viral Infections ◽

Driving Forces ◽

Cell Spreading ◽

Cell Contact ◽

Virus Release ◽

Cell Tissue ◽

Cell Transmission ◽

Cell Spread ◽

Cell Cell

ABSTRACT Viral infections spread based on the ability of viruses to overcome multiple barriers and move from cell to cell, tissue to tissue, and person to person and even across species. While there are fundamental differences between these types of transmissions, it has emerged that the ability of viruses to utilize and manipulate cell-cell contact contributes to the success of viral infections. Central to the excitement in the field of virus cell-to-cell transmission is the idea that cell-to-cell spread is more than the sum of the processes of virus release and entry. This implies that virus release and entry are efficiently coordinated to sites of cell-cell contact, resulting in a process that is distinct from its individual components. In this review, we will present support for this model, illustrate the ability of viruses to utilize and manipulate cell adhesion molecules, and discuss the mechanism and driving forces of directional spreading. An understanding of viral cell-to-cell spreading will enhance our ability to intervene in the efficient spreading of viral infections.

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Recruitment and activation of Rac1 by the formation of E-cadherin-mediated cell-cell adhesion sites

Journal of Cell Science ◽

10.1242/jcs.114.10.1829 ◽

2001 ◽

Vol 114 (10) ◽

pp. 1829-1838 ◽

Cited By ~ 4

Author(s):

M. Nakagawa ◽

M. Fukata ◽

M. Yamaga ◽

N. Itoh ◽

K. Kaibuchi

Keyword(s):

Cell Adhesion ◽

Specific Binding ◽

Green Fluorescence Protein ◽

Neutralizing Antibody ◽

Small Gtpases ◽

Cell Contact ◽

Adhesion Sites ◽

P21 Activated Kinase ◽

E Cadherin ◽

Cell Cell

Rac1, a member of the Ρ family small GTPases, regulates E-cadherin-mediated cell-cell adhesion. However, it remains to be clarified how the localization and activation of Rac1 are regulated at sites of cell-cell contact. Here, using enhanced green fluorescence protein (EGFP)-tagged Rac1, we demonstrate that EGFP-Rac1 is colocalized with E-cadherin at sites of cell-cell contact and translocates to the cytosol during disruption of E-cadherin-mediated cell-cell adhesion by Ca(2+) chelation. Re-establishment of cell-cell adhesion by restoration of Ca(2)(+) caused EGFP-Rac1 to become relocalized, together with E-cadherin, at sites of cell-cell contact. Engagement of E-cadherin to the apical membrane by anti-E-cadherin antibody (ECCD-2) recruited EGFP-Rac1. We also investigated whether E-cadherin-mediated cell-cell adhesion induced Rac1 activation by measuring the amounts of GTP-bound Rac1 based on its specific binding to the Cdc42/Rac1 interactive binding region of p21-activated kinase. The formation of E-cadherin-mediated cell-cell adhesion induced Rac1 activation. This activation was inhibited by treatment of cells with a neutralizing antibody (DECMA-1) against E-cadherin, or with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase). IQGAP1, an effector of Rac1, and EGFP-Rac1 behaved in a similar manner during the formation of E-cadherin-mediated cell-cell adhesion. Rac1 activation was also confirmed by measuring the amounts of coimmunoprecipitated Rac1 with IQGAP1 during the establishment of cell-cell adhesion. Taken together, these results suggest that Rac1 is recruited at sites of E-cadherin-mediated cell-cell adhesion and then activated, possibly through PI 3-kinase. http://www/biologists.com/JCS/movies/jcs2094.html

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Cell-to-Cell Spread of Dengue Viral RNA in Mosquito Cells

BioMed Research International ◽

10.1155/2020/2452409 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Chih-Chieh Cheng ◽

Chao-Fu Yang ◽

Yin-Ping Lo ◽

Yi-Hsuan Chiang ◽

Eny Sofiyatun ◽

...

Keyword(s):

Gradient Centrifugation ◽

Denv Infection ◽

Viral Rna ◽

Cell Contact ◽

Mosquito Vector ◽

Viral Spread ◽

Mosquito Cells ◽

Host Membrane ◽

Cell Transmission ◽

Cell Cell

Dengue virus (DENV) is an important mosquito-borne arbovirus that is particularly prevalent in tropical and subtropical areas of the world. The virus is generally ingested with a blood meal, replicates in host tissues, and disseminates into salivary glands for transmission to the next host. Membrane-bound vacuoles carrying DENV particles have been documented in mosquito cells and play a role in the cell-to-cell transmission of DENV2. C189 is one member of the tetraspanin family and generally increases its expression as one component of the vacuoles (C189-VCs) within C6/36 cells infected with DENV2. In the present study, we have further demonstrated via sucrose gradient centrifugation as well as magnetic immune isolation (MI) that the RNA of DENV2 was eventually carried by C189-VCs. In addition, viral RNA was shown to spread from donor to recipient cells in a coculture assay even when 20 mM NH4Cl was added to inhibit virus replication in the culture. In an alternate assay using the transwell system, viral RNA was only detected in recipient cells in the absence of 40 mM NH4Cl, suggesting that cell-cell contact is required for the intercellular spread of DENV2. In turn, the formation of viral synapse (VS) derived from aggregates of viral particles was frequently observed at sites of cell contact. Taken together, the formation of C189-VCs in C6/36 cells is induced by DENV2 infection, which may serve as a vehicle for transferring virions and also viral RNA to neighboring cells by cell-to-cell transmission after cell-cell contact. This finding provides insight into the understanding of viral spread between mosquito cells. It may also elucidate the benign persistent infection in mosquito cells and efficient dissemination of DENV infection within a mosquito vector.

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