Comput Struct Biotechnol J. 2020 ;18
2836-2850
The Zika virus is a flavivirus that can cause fulminant outbreaks and lead to Guillain-Barré syndrome, microcephaly and fetal demise. Like other flaviviruses, the Zika virus is transmitted by mosquitoes and provokes neurological disorders. Despite its risk to public health, no antiviral nor vaccine are currently available. In the recent years, several studies have set to identify human host proteins interacting with Zika viral proteins to better understand its pathogenicity. Yet these studies used standard human protein sequence databases. Such databases rely on genome annotations, which enforce a minimal open reading frame (ORF) length criterion. An ever-increasing number of studies have demonstrated the shortcomings of such annotation, which overlooks thousands of functional ORFs. Here we show that the use of a customized database including currently non-annotated proteins led to the identification of 4 alternative proteins as interactors of the viral capsid and NS4A proteins. Furthermore, 12 alternative proteins were identified in the proteome profiling of Zika infected monocytes, one of which was significantly up-regulated. This study presents a computational framework for the re-analysis of proteomics datasets to better investigate the viral-host protein interplays upon infection with the Zika virus.
Keywords: AP-MS, affinity-purification mass spectrometry; Alternative ORFs; DEP, differentially expressed proteins; FDR, false discovery rate; FPKM, fragments per kilobase of exon model per million reads mapped; Flavivirus; HCIP, highly confident interacting proteins; HCMV, human cytomegalovirus; LFQ, label free quantification; MS, mass spectrometry; ORF, open reading frame; PSM, peptide spectrum match; Protein network; Proteogenomics; Proteome profiling; ZIKV, Zika virus; Zika; altProt, alternative protein; ncRNA, non-coding RNA; sORF, small open reading frame