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.
Highlights
Viruses are highly adapted intracellular pathogens that co-evolved with their hosts over millions of years
Using an affinity purification (AP)-LC-Mass spectrometry (MS)/MS approach in SK-N-BE2 neuroblastoma cells [34], we identified in the Zika virus (ZIKV) capsid interactome a strong enrichment in nuclear and nucleolar-resident proteins such as nucleolin (NCL), nucleolar RNA-dependent helicases of the DDX family, core histones (H2A), as well as peroxisomal proteins including Pex19, that have been previously reported as cellular targets of Dengue (DENV) and West Nile virus (WNV) (Figure 2b) [35,36,37]
While the antiviral activity of individual members of these complexes appears moderate in knock-down studies, further experimental evidence supports a direct interaction between the viral RNA and RBM8A, suggesting a depletion of the cellular PYM1 pool upon recruitment by the WNV capsid to protect viral
Summary
Viruses are highly adapted intracellular pathogens that co-evolved with their hosts over millions of years This resulted in a sophisticated adaptation that allowed viruses to engross cellular machineries for their own replication, with the benefit to encode their genetic information with high efficiency. Technological developments in the fields of genomics and proteomics became available in recent years, allowing to systematically map interactions between viruses and their hosts in an unbiased manner Such interactions are of particular interest especially when uncharacterized pathogens strike in a naïve population. The limited knowledge on ZIKV pathogenesis and the sudden spread of this pathogen sparked a number of independent laboratories to characterize the virus–host interactions on a molecular level These studies are of particular interest, since ZIKV combines many unique features of flaviviruses that are normally limited to individual species. We review current approaches, in particular proteomic-based datasets, which have been used to identify ZIKV–host interactions
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