Intact sphingomyelin biosynthetic pathway is essential for intracellular transport of influenza virus glycoproteins

Fikadu Tafesse, Sumana Sanyal, Joseph Ashour, Carla P. Guimaraes, Martin Hermansson, Pentti Somerharju, Hidde L. Ploegh

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Cells genetically deficient in sphingomyelin synthase-1 (SGMS1) or blocked in their synthesis pharmacologically through exposure to a serine palmitoyltransferase inhibitor (myriocin) show strongly reduced surface display of influenza virus glycoproteins hemag-glutinin (HA) and neuraminidase (NA). The transport of HA to the cell surface was assessed by accessibility of HA on intact cells to exogenously added trypsin and to HA-specific antibodies. Rates of de novo synthesis of viral proteins in wild-type and SGMS1-deficient cells were equivalent, and HA negotiated the intracellular trafficking pathway through the Golgi normally. We engineered a strain of influenza virus to allow site-specific labeling of HA and NA using sortase. Accessibility of both HA and NA to sortase was blocked in SGMS1-deficient cells and in cells exposed to myriocin, with a corresponding inhibition of the release of virus particles from infected cells. Generation of influenza virus particles thus critically relies on a functional sphingomyelin biosynthetic pathway, required to drive influenza viral glycoproteins into lipid domains of a composition compatible with virus budding and release.

Original languageEnglish (US)
Pages (from-to)6406-6411
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number16
DOIs
StatePublished - Apr 16 2013
Externally publishedYes

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Sphingomyelins
Biosynthetic Pathways
Orthomyxoviridae
Glycoproteins
Neuraminidase
Virus Release
Virion
Serine C-Palmitoyltransferase
Viral Proteins
Trypsin
Human Influenza
Lipids
Antibodies
phosphatidylcholine-ceramide phosphocholine transferase

ASJC Scopus subject areas

  • General

Cite this

Intact sphingomyelin biosynthetic pathway is essential for intracellular transport of influenza virus glycoproteins. / Tafesse, Fikadu; Sanyal, Sumana; Ashour, Joseph; Guimaraes, Carla P.; Hermansson, Martin; Somerharju, Pentti; Ploegh, Hidde L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 16, 16.04.2013, p. 6406-6411.

Research output: Contribution to journalArticle

Tafesse, Fikadu ; Sanyal, Sumana ; Ashour, Joseph ; Guimaraes, Carla P. ; Hermansson, Martin ; Somerharju, Pentti ; Ploegh, Hidde L. / Intact sphingomyelin biosynthetic pathway is essential for intracellular transport of influenza virus glycoproteins. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 16. pp. 6406-6411.
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