Role of the Phosphatidylserine Receptor TIM-1 in Enveloped-Virus Entry

  • Moller-Tank S
  • Kondratowicz A
  • Davey R
  • et al.
203Citations
Citations of this article
264Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The cell surface receptor T cell immunoglobulin mucin domain 1 (TIM-1) dramatically enhances filovirus infection of epithelial cells. Here, we showed that key phosphatidylserine (PtdSer) binding residues of the TIM-1 IgV domain are critical for Ebola virus (EBOV) entry through direct interaction with PtdSer on the viral envelope. PtdSer liposomes but not phosphatidylcholine liposomes competed with TIM-1 for EBOV pseudovirion binding and transduction. Further, annexin V (AnxV) substituted for the TIM-1 IgV domain, supporting a PtdSer-dependent mechanism. Our findings suggest that TIM-1-dependent uptake of EBOV occurs by apoptotic mimicry. Additionally, TIM-1 enhanced infection of a wide range of enveloped viruses, including alphaviruses and a baculovirus. As further evidence of the critical role of enveloped-virion-associated PtdSer in TIM-1-mediated uptake, TIM-1 enhanced internalization of pseudovirions and virus-like proteins (VLPs) lacking a glycoprotein, providing evidence that TIM-1 and PtdSer-binding receptors can mediate virus uptake independent of a glycoprotein. These results provide evidence for a broad role of TIM-1 as a PtdSer-binding receptor that mediates enveloped-virus uptake. Utilization of PtdSer-binding receptors may explain the wide tropism of many of these viruses and provide new avenues for controlling their virulence.

Cite

CITATION STYLE

APA

Moller-Tank, S., Kondratowicz, A. S., Davey, R. A., Rennert, P. D., & Maury, W. (2013). Role of the Phosphatidylserine Receptor TIM-1 in Enveloped-Virus Entry. Journal of Virology, 87(15), 8327–8341. https://doi.org/10.1128/jvi.01025-13

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free