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Review
. 2019 Sep 19;11(9):878.
doi: 10.3390/v11090878.

Chasing Intracellular Zika Virus Using Proteomics

Pietro Scaturro  1 , Anna Lena Kastner  2 , Andreas Pichlmair  3   4
Affiliations
Review

Chasing Intracellular Zika Virus Using Proteomics

Pietro Scaturro et al. Viruses. .

Abstract

Flaviviruses are the most medically relevant group of arboviruses causing a wide range of diseases in humans and are associated with high mortality and morbidity, as such posing a major health concern. Viruses belonging to this family can be endemic (e.g., dengue virus), but can also cause fulminant outbreaks (e.g., West Nile virus, Japanese encephalitis virus and Zika virus). Intense research efforts in the past decades uncovered shared fundamental strategies used by flaviviruses to successfully replicate in their respective hosts. However, the distinct features contributing to the specific host and tissue tropism as well as the pathological outcomes unique to each individual flavivirus are still largely elusive. The profound footprint of individual viruses on their respective hosts can be investigated using novel technologies in the field of proteomics that have rapidly developed over the last decade. An unprecedented sensitivity and throughput of mass spectrometers, combined with the development of new sample preparation and bioinformatics analysis methods, have made the systematic investigation of virus-host interactions possible. Furthermore, the ability to assess dynamic alterations in protein abundances, protein turnover rates and post-translational modifications occurring in infected cells now offer the unique possibility to unravel complex viral perturbations induced in the infected host. In this review, we discuss the most recent contributions of mass spectrometry-based proteomic approaches in flavivirus biology with a special focus on Zika virus, and their basic and translational potential and implications in understanding and characterizing host responses to arboviral infections.

Keywords: AP-LC-MS/MS; DENV; Label-free Quatification; WNV; Zika virus; arboviruses; flaviviruses; interactome; phosphoproteomics; proteomics.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
– Omics methods to study virus-induced cellular perturbations. The key advantages of Interaction proteomics (affinity purification mass spectrometry, AP-MS), expression proteomics and next generation sequencing (NGS) in studying flavivirus-induced perturbations are listed within each square. Colors indicate the respective step(s) of the viral replication cycles predominantly targeted by each method. Abbreviations: PTMs, post-translational modifications.
Figure 2
Figure 2
– Recently identified cellular interactors of flavivirus capsids and NS4Bs. (a) Schematic representation of flavivirus viral proteins and respective membrane topology. (b) Capsid interactors reported to bind exclusively to Zika virus (ZIKV)-C are surrounded by the light blue circle, while those within the orange circle were reported as shared interactors of ZIKV, West Nile virus (WNV) and Dengue (DENV)-C. The respective sub-cellular localization is indicated. (c) NS4B interactors reported to bind exclusively to ZIKV-NS4B are shown in blue, while those shared with DENV-NS4B are shown in green. Mitochondrial- and endoplasmic-reticulum-resident proteins are surrounded by green and orange circles, respectively. Proteins with functions associated to ZIKV-related pathologies are surrounded by the blue circle. All gene names and corresponding full protein names are listed in Table 1.
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