RPLP1 and RPLP2 are essential flavivirus host factors that promote early viral protein accumulation

Rafael Kroon Campos, Benjamin Wong, Xuping Xie, Yi Fan Lu, Pei-Yong Shi, Julien Pompon, Mariano Garcia-Blanco, Shelton Bradrick

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The Flavivirus genus contains several arthropod-borne viruses that pose global health threats, including dengue viruses (DENV), yellow fever virus (YFV), and Zika virus (ZIKV). In order to understand how these viruses replicate in human cells, we previously conducted genome-scale RNA interference screens to identify candidate host factors. In these screens, we identified ribosomal proteins RPLP1 and RPLP2 (RPLP1/2) to be among the most crucial putative host factors required for DENV and YFV infection. RPLP1/2 are phosphoproteins that bind the ribosome through interaction with another ribosomal protein, RPLP0, to form a structure termed the ribosomal stalk. RPLP1/2 were validated as essential host factors for DENV, YFV, and ZIKV infection in two human cell lines: A549 lung adenocarcinoma and HuH-7 hepatoma cells, and for productive DENV infection of Aedes aegypti mosquitoes. Depletion of RPLP1/2 caused moderate cell-line-specific effects on global protein synthesis, as determined by metabolic labeling. In A549 cells, global translation was increased, while in HuH-7 cells it was reduced, albeit both of these effects were modest. In contrast, RPLP1/2 knockdown strongly reduced early DENV protein accumulation, suggesting a requirement for RPLP1/2 in viral translation. Furthermore, knockdown of RPLP1/2 reduced levels of DENV structural proteins expressed from an exogenous transgene. We postulate that these ribosomal proteins are required for efficient translation elongation through the viral open reading frame. In summary, this work identifies RPLP1/2 as critical flaviviral host factors required for translation.

Original languageEnglish (US)
Article numbere01706-16
JournalJournal of Virology
Volume91
Issue number4
DOIs
StatePublished - 2017

Fingerprint

Flavivirus
Dengue virus
Dengue Virus
viral proteins
Viral Proteins
Yellow fever virus
Zika virus
translation (genetics)
Ribosomal Proteins
ribosomal proteins
Virus Diseases
infection
cells
Viral Structural Proteins
Arboviruses
vertebrate viruses
arboviruses
phosphoproteins
human cell lines
Dengue

Keywords

  • Flavivirus
  • Ribosomal proteins
  • Translation

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

RPLP1 and RPLP2 are essential flavivirus host factors that promote early viral protein accumulation. / Kroon Campos, Rafael; Wong, Benjamin; Xie, Xuping; Lu, Yi Fan; Shi, Pei-Yong; Pompon, Julien; Garcia-Blanco, Mariano; Bradrick, Shelton.

In: Journal of Virology, Vol. 91, No. 4, e01706-16, 2017.

Research output: Contribution to journalArticle

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