Disruption of Phosphatidylserine Synthesis or Trafficking Reduces Infectivity of Ebola Virus

Patrick Younan, Mathieu Iampietro, Rodrigo I. Santos, Palaniappan Ramanathan, Vsevolod Popov, Alexander Bukreyev

Research output: Contribution to journalArticle

Abstract

The outer leaflet of the viral membrane of Ebola virus (EBOV) virions is enriched with phosphatidylserine (PtdSer), which is thought to play a central role in viral tropism, entry, and virus-associated immune evasion. We investigated the effects of inhibiting synthesis and/or export of PtdSer to the cell surface of infected cells on viral infectivity. Knockdown of both PtdSer synthase enzymes, PTDSS1 and PTDSS2, effectively decreased viral production. Decreased PtdSer expression resulted in an accumulation of virions at the plasma membrane and adjacent of intracellular organelles, suggesting that virion budding is impaired. The addition of inhibitors that block normal cellular trafficking of PtdSer to the plasma membrane resulted in a similar accumulation of virions and reduced viral replication. These findings demonstrate that plasma membrane-associated PtdSer is required for efficient EBOV budding, increasing EBOV infectivity, and could constitute a potential therapeutic target for the development of future countermeasures against EBOV.

Original languageEnglish (US)
Pages (from-to)S475-S485
JournalThe Journal of infectious diseases
Volume218
Issue number5
DOIs
StatePublished - Nov 22 2018

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Ebolavirus
Phosphatidylserines
Virion
Cell Membrane
CDPdiacylglycerol-Serine O-Phosphatidyltransferase
Viral Tropism
Virus Release
Immune Evasion
Virus Internalization
Organelles
Membranes
Enzymes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Disruption of Phosphatidylserine Synthesis or Trafficking Reduces Infectivity of Ebola Virus. / Younan, Patrick; Iampietro, Mathieu; Santos, Rodrigo I.; Ramanathan, Palaniappan; Popov, Vsevolod; Bukreyev, Alexander.

In: The Journal of infectious diseases, Vol. 218, No. 5, 22.11.2018, p. S475-S485.

Research output: Contribution to journalArticle

Younan, Patrick ; Iampietro, Mathieu ; Santos, Rodrigo I. ; Ramanathan, Palaniappan ; Popov, Vsevolod ; Bukreyev, Alexander. / Disruption of Phosphatidylserine Synthesis or Trafficking Reduces Infectivity of Ebola Virus. In: The Journal of infectious diseases. 2018 ; Vol. 218, No. 5. pp. S475-S485.
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