@article{fdi:010069299,
  title = {{RPLP}1 and {RPLP}2 are essential flavivirus host factors that promote early viral protein accumulation},
  author = {{C}ampos, {R}. {K}. and {W}ong, {B}. and {X}ie, {X}. {P}. and {L}u, {Y}. {F}. and {S}hi, {P}. {Y}. and {P}ompon, {J}ulien and {G}arcia-{B}lanco, {M}. {A}. and {B}radrick, {S}. {S}.},
  editor = {},
  language = {{ENG}},
  abstract = {{T}he {F}lavivirus genus contains several arthropod-borne viruses that pose global health threats, including dengue viruses ({DENV}), yellow fever virus ({YFV}), and {Z}ika virus ({ZIKV}). {I}n order to understand how these viruses replicate in human cells, we previously conducted genome-scale {RNA} interference screens to identify candidate host factors. {I}n these screens, we identified ribosomal proteins {RPLP}1 and {RPLP}2 ({RPLP}1/2) to be among the most crucial putative host factors required for {DENV} and {YFV} infection. {RPLP}1/2 are phosphoproteins that bind the ribosome through interaction with another ribosomal protein, {RPLP}0, to form a structure termed the ribosomal stalk. {RPLP}1/2 were validated as essential host factors for {DENV}, {YFV}, and {ZIKV} infection in two human cell lines: {A}549 lung adenocarcinoma and {H}u{H}-7 hepatoma cells, and for productive {DENV} infection of {A}edes aegypti mosquitoes. {D}epletion of {RPLP}1/2 caused moderate cell-line-specific effects on global protein synthesis, as determined by metabolic labeling. {I}n {A}549 cells, global translation was increased, while in {H}u{H}-7 cells it was reduced, albeit both of these effects were modest. {I}n contrast, {RPLP}1/2 knockdown strongly reduced early {DENV} protein accumulation, suggesting a requirement for {RPLP}1/2 in viral translation. {F}urthermore, knockdown of {RPLP}1/2 reduced levels of {DENV} structural proteins expressed from an exogenous transgene. {W}e postulate that these ribosomal proteins are required for efficient translation elongation through the viral open reading frame. {I}n summary, this work identifies {RPLP}1/2 as critical flaviviral host factors required for translation. {IMPORTANCE} {F}laviviruses cause important diseases in humans. {E}xamples of mosquito-transmitted flaviviruses include dengue, yellow fever and {Z}ika viruses. {V}iruses require a plethora of cellular factors to infect cells, and the ribosome plays an essential role in all viral infections. {T}he ribosome is a complex macromolecular machine composed of {RNA} and proteins and it is responsible for protein synthesis. {W}e identified two specific ribosomal proteins that are strictly required for flavivirus infection of human cells and mosquitoes: {RPLP}1 and {RPLP}2 ({RPLP}1/2). {T}hese proteins are part of a structure known as the ribosomal stalk and help orchestrate the elongation phase of translation. {W}e show that flaviviruses are particularly dependent on the function of {RPLP}1/2. {O}ur findings suggest that ribosome composition is an important factor for virus translation and may represent a regulatory layer for translation of specific cellular m{RNA}s.},
  keywords = {flavivirus ; ribosomal proteins ; translation},
  booktitle = {},
  journal = {{J}ournal of {V}irology},
  volume = {91},
  numero = {4},
  pages = {e01706--16 [17p.]},
  ISSN = {0022-538{X}},
  year = {2017},
  DOI = {10.1128/jvi.01706-16},
  URL = {https://www.documentation.ird.fr/hor/fdi:010069299},
}