The cytoplasmic domain of marburg virus GP modulates early steps of viral infection

Eva-Maria Mittler, Larissa Kolesnikova, Bettina Hartlieb, Robert Davey, Stephan Becker

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Marburg virus infection is mediated by the only viral surface protein, GP, a trimeric type I transmembrane protein. While its ectodomain mediates receptor binding and fusion of viral and cellular membranes and its transmembrane domain is essential for the recruitment of GP into budding particles by the matrix protein VP40, the role of the short cytoplasmic domain has remained enigmatic. Here we show that a missing cytoplasmic domain did not impair trimerization, intracellular transport, or incorporation of GP into infectious Marburg virus-like particles (iVLPs) but altered the glycosylation pattern as well as the recognition of GP by neutralizing antibodies. These results suggest that subtle conformational changes took place in the ectodomain. To investigate the function of the cytoplasmic domain during viral entry, a novel entry assay was established to monitor the uptake of filamentous VLPs by measuring the occurrence of luciferase-labeled viral nucleocapsids in the cytosol of target cells. This quantitative assay showed that the entry process of VLPs incorporating GP missing its cytoplasmic domain (GPΔCD) was impaired. Supporting these results, iVLPs incorporating a mutant GP missing its cytoplasmic domain were significantly less infectious than iVLPs containing wild-type GP. Taken together, the data indicate that the absence of the short cytoplasmic domain of Marburg virus GP may induce conformational changes in the ectodomain which impact the filoviral entry process.

Original languageEnglish (US)
Pages (from-to)8188-8196
Number of pages9
JournalJournal of Virology
Volume85
Issue number16
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Fingerprint

Marburg virus
Marburgvirus
Virus Diseases
virus-like particles
Virion
infection
Nucleocapsid
nucleocapsid
Virus Internalization
transmembrane proteins
viral proteins
surface proteins
Viral Proteins
assays
luciferase
glycosylation
Neutralizing Antibodies
Luciferases
Glycosylation
neutralizing antibodies

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

The cytoplasmic domain of marburg virus GP modulates early steps of viral infection. / Mittler, Eva-Maria; Kolesnikova, Larissa; Hartlieb, Bettina; Davey, Robert; Becker, Stephan.

In: Journal of Virology, Vol. 85, No. 16, 01.01.2011, p. 8188-8196.

Research output: Contribution to journalArticle

Mittler, Eva-Maria ; Kolesnikova, Larissa ; Hartlieb, Bettina ; Davey, Robert ; Becker, Stephan. / The cytoplasmic domain of marburg virus GP modulates early steps of viral infection. In: Journal of Virology. 2011 ; Vol. 85, No. 16. pp. 8188-8196.
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