Deschamps, Thibaut and Dogrammatzis, Christos and Mullick, Ranajoy and Kalamvoki, Maria and Longnecker, Richard M (2017) Cbl E3 Ligase Mediates the Removal of Nectin-1 from the Surface of Herpes Simplex Virus 1-Infected Cells. In: Journal of Virology, 91 (12). ISSN 0022-538X
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Abstract
The Cbl E3 ligase has been linked to the down-modulation of surface signaling responses by inducing internalization of surface receptors. The adaptor protein CIN85 is a partner of Cbl that augments many of these interactions. Previously, an interaction was demonstrated between ICP0 and CIN85, which results in the removal of epidermal growth factor receptor (EGFR) from the surface of the infected cells with a concomitant attenuation of EGFR signaling. Here, we examined whether Cbl mediates the removal of the herpes simplex virus 1 (HSV-1) entry receptor Nectin-1 from the surface of infected cells. We found the following: (i) that Cbl, Nectin-1, and the viral glycoprotein D (gD) form a complex in infected cells; (ii) that during infection Nectin-1 is removed from the surface of the infected cells but is retained on the surface of cells that have been depleted of Cbl; and (iii) that in cells infected with a ΔICP0 mutant virus, Nectin-1 remained on the cell surface. Thus, Cbl is necessary but not sufficient for the removal of Nectin-1 from the cell surface. In addition, we observed that in Cbl-depleted cells there was enhanced entry after infection. These cells were susceptible to secondary infections by HSV-1. Viral entry in CIN85-depleted cells was only moderately enhanced compared to that in the Cbldepleted cells, suggesting that the Cbl-Nectin-1 interaction is likely the key to the downregulation of surface Nectin-1. The removal of the HSV-1 entry receptor Nectin-1 from the surface of the infected cells may be part of the strategy of the virus to efficiently spread to uninfected cells.
| Item Type: | Journal Article |
|---|---|
| Publication: | Journal of Virology |
| Publisher: | American Society for Microbiology |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | Cbl E3 ligase; Cell surface; Endocytosis; HSV-1; ICP0; Nectin-1 |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 14 Jun 2022 05:42 |
| Last Modified: | 14 Jun 2022 05:42 |
| URI: | https://eprints.iisc.ac.in/id/eprint/73448 |
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