Abstract
Newly re-emerging viruses are of great global concern, especially when there are no therapeutic interventions available during the time of an outbreak. There are still no therapeutic interventions for the prevention of Zika virus (ZIKV) infections despite its resurgence more than a decade ago. Newborns infected with ZIKV suffer from microcephaly and delayed neurodevelopment, but the underlying causes are largely unknown. All viruses hijack the host cellular machinery to undergo successful replication. Our tandem mass tag mass spectrometry-based proteomic monitoring of cells infected with ZIKV revealed that among the thousands of host proteins dysregulated over time, many protein candidates were linked to neurodevelopmental processes, including the development of the auditory and visual/retinal system. The role of these dysregulated neurodevelopmental-associated host proteins for ZIKV propagation in eukaryotic cells remains elusive. For the first time, we present temporal neurodevelopmental proteomic responses in cells undergoing ZIKV infection. The future goal is to identify host proteins whose dysregulation results in neurosensory alterations reported in children born to ZIKV-infected mothers.
Highlights
Zika virus (ZIKV), an arthropod-borne virus, has been known for decades, but useful therapeutic interventions are still lacking
We identified a total of 7,455 cellular protein hits across all time points, with 6,443, 6,402, and 6,382 proteins identified at 12, 24, and 48 hpi, respectively (Supplementary Table S1)
Because the Tandem mass tags (TMT) analysis reports ZIKV:mock peptide and protein ratios, and ZIKV proteins are not expected in the mock samples, the ZIKV proteins are not considered hereafter
Summary
Zika virus (ZIKV), an arthropod-borne virus, has been known for decades, but useful therapeutic interventions are still lacking. There were global concerns when a high prevalence of ZIKV infections was reported in numerous countries in the early 2000s (Brasil et al, 2016). RNA nucleic acid testing is currently used to confirm ZIKV infections in suspected infected patients. Zika Virus Proteomics women are at high risk since the virus can cross the placenta and infect the developing fetus. ZIKV transplacental transmission was confirmed by detecting viral proteins and RNA in placental tissue samples from expectant mothers infected at different stages during pregnancy (Calvet et al, 2016; Martines et al, 2016; Sarno et al, 2016). Infection of the developing fetus leads to congenital abnormalities collectively known as Congenital Zika Syndrome (CZS) (Moore et al, 2017). CZS is characterized by a spectrum of neurological disorders in infants ranging from mild to severe brain damage with or without microcephaly, to severe forms that result in intrauterine death (Besnard et al, 2016; Schuler-Faccini et al, 2016)
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