Rab18 facilitates dengue virus infection by targeting fatty acid synthase to sites of viral replication

Wei Chun Tang, Ren Jye Lin, Ching Len Liao, Yi Ling Lin

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Positive-sense RNA viruses, such as dengue virus (DENV), hijack the intracellular membrane machinery for their own replication. The Rab18 protein, a member of the Rab GTPase family, key regulators of membrane trafficking, is located on the organelles involved in DENV infection, such as the endoplasmic reticulum (ER) and lipid droplets (LDs). In this study, we addressed the potential involvement of Rab18 in DENV infection by using cells overexpressing the wild-type, GTP-bound active form, or GDP-bound inactive form of Rab18 and cells with Rab18 knockdown. DENV replication, measured by viral protein, viral RNA, and viral progeny production, as well as LD induction, was reduced in cells with inactive Rab18 and in cells deprived of Rab18 expression, suggesting a positive role of Rab18 in the DENV life cycle. Interestingly, the interaction of fatty acid synthase (FASN), a key lipogenic enzyme in lipid biosynthesis, with DENV NS3 protein relied on the conversion of the GDP-bound to the GTP-bound form of Rab18. Furthermore, the targeting of FASN to sites participating in DENV infection, such as the ER and LDs, depends on functional Rab18. Thus, Rab18-mediated membrane trafficking of FASN and NS3 facilitates DENV replication, probably by ensuring a sufficient and coordinated lipid supply for membrane proliferation and arrangement.

Original languageEnglish
Pages (from-to)6793-6804
Number of pages12
JournalJournal of Virology
Volume88
Issue number12
DOIs
Publication statusPublished - 2014

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Fatty Acid Synthases
Dengue virus
fatty-acid synthase
Dengue Virus
Virus Diseases
virus replication
infection
droplets
lipids
Virus Replication
Guanosine Triphosphate
Endoplasmic Reticulum
endoplasmic reticulum
rab GTP-Binding Proteins
positive sense, single-stranded RNA viruses
Intracellular Membranes
cells
Membranes
RNA Viruses
Viral RNA

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Rab18 facilitates dengue virus infection by targeting fatty acid synthase to sites of viral replication. / Tang, Wei Chun; Lin, Ren Jye; Liao, Ching Len; Lin, Yi Ling.

In: Journal of Virology, Vol. 88, No. 12, 2014, p. 6793-6804.

Research output: Contribution to journalArticle

Tang, Wei Chun ; Lin, Ren Jye ; Liao, Ching Len ; Lin, Yi Ling. / Rab18 facilitates dengue virus infection by targeting fatty acid synthase to sites of viral replication. In: Journal of Virology. 2014 ; Vol. 88, No. 12. pp. 6793-6804.
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