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A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
04:23

A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease

Published on: April 28, 2019

Functional importance of dengue virus maturation: infectious properties of immature virions

Izabela A Zybert1, Heidi van der Ende-Metselaar1, Jan Wilschut1

  • 1Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.

The Journal of General Virology
|November 15, 2008
PubMed

Insights

Immature dengue virus (DENV) particles containing uncleaved prM protein are not infectious. This study demonstrates that prM cleavage to M is essential for DENV infectivity, challenging previous assumptions.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • Flavivirus maturation involves cleavage of the prM protein to M by furin.
  • Dengue virus (DENV) maturation is inefficient, with many progeny virions retaining uncleaved prM.
  • Previous studies suggested prM-containing DENV particles are infectious, contradicting the necessity of prM processing.

Purpose of the Study:

  • To re-evaluate the infectious properties of immature DENV virions.
  • To determine if prM cleavage is essential for DENV infectivity.

Main Methods:

  • Production of DENV particles in furin-deficient LoVo cells.
  • Quantification of prM-containing particles secreted by infected cells.
  • Assessment of the infectivity of immature DENV particles.

Main Results:

  • Furin-deficient cells produced high numbers of DENV particles containing uncleaved prM.
  • Immature DENV particles exhibited significantly reduced infectivity.
  • The infectious unit to particle ratio was 10,000-fold lower for immature particles compared to wild-type DENV.

Conclusions:

  • Cleavage of the prM protein to M is required for Dengue virus infectivity.
  • Immature DENV particles are not infectious, refuting prior assumptions.
  • Efficient prM processing is critical for the generation of infectious DENV virions.

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