Super resolution microscopy and deep learning identify Zika virus reorganization of the endoplasmic reticulum.

Journal: Scientific reports
PMID:

Abstract

The endoplasmic reticulum (ER) is a complex subcellular organelle composed of diverse structures such as tubules, sheets and tubular matrices. Flaviviruses such as Zika virus (ZIKV) induce reorganization of ER membranes to facilitate viral replication. Here, using 3D super resolution microscopy, ZIKV infection is shown to induce the formation of dense tubular matrices associated with viral replication in the central ER. Viral non-structural proteins NS4B and NS2B associate with replication complexes within the ZIKV-induced tubular matrix and exhibit distinct ER distributions outside this central ER region. Deep neural networks trained to distinguish ZIKV-infected versus mock-infected cells successfully identified ZIKV-induced central ER tubular matrices as a determinant of viral infection. Super resolution microscopy and deep learning are therefore able to identify and localize morphological features of the ER and allow for better understanding of how ER morphology changes due to viral infection.

Authors

  • Rory K M Long
    Life Sciences Institute, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
  • Kathleen P Moriarty
    School of Computing Science, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Ben Cardoen
    School of Computing Science, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • Guang Gao
    Life Sciences Institute, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
  • A Wayne Vogl
    Life Sciences Institute, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
  • François Jean
    Life Sciences Institute, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. fjean@mail.ubc.ca.
  • Ghassan Hamarneh
    Medical Image Analysis Lab, Simon Fraser University, Burnaby, BC, Canada. Electronic address: hamarneh@sfu.ca.
  • Ivan R Nabi
    Life Sciences Institute, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. irnabi@mail.ubc.ca.