Differential proteomics of Zika virus (ZIKV) infection reveals molecular changes potentially involved in immune system evasion by a Brazilian strain of ZIKV

Zika virus (ZIKV) is an arbovirus that was responsible for multiple outbreaks from 2007 to 2015. It has been linked to cases of microcephaly in Brazil in 2015, among other neurological disorders. Differences among strains might be the reason for different clinical outcomes of infection. To evaluate this hypothesis, we performed a comparative proteomic analysis of Vero cells infected with the African strain MR766 (ZIKVAFR) and the Brazilian strain 17 SM (ZIKVBR). A total of 550 proteins were identified as differentially expressed in ZIKVAFR- or ZIKVBR-infected cells compared to the control. The main findings included upregulation of immune system pathways (neutrophil degranulation and adaptive/innate immune system) and potential activation of immune-system-related pathways by ZIKVAFR (mTOR, JAK-STAT, NF-κB, and others) compared with the ZIKVBR/control. In addition, phagocytosis by macrophages and engulfment of leukocytes were activated in ZIKVAFR infection. An in vivo analysis using an immunocompetent C57BL/6N mouse model identified interstitial pneumonia with neutrophil infiltration in the lungs only in mice infected with ZIKVBR at 48 hours postinfection, with a significant amount of virus detected. Likewise, only animals infected with ZIKVBR had viral material in the cytoplasm of lung macrophages. These results suggest that activation of the immune system by ZIKVAFR infection may lead to faster viral clearance by immune cells.