Role of Zika Virus prM Protein in Viral Pathogenicity and Use in Vaccine Development.

Peter Nambala,Wen-Chi Su

doi:10.3389/fmicb.2018.01797

Abstract

Recent Zika virus (ZIKV) epidemics necessitate the urgent development of effective drugs and vaccines, which can be accelerated by an enhanced understanding of ZIKV biology. One of the ZIKV structural proteins, precursor membrane (prM), plays an important role in the assembly of mature virions through cleavage of prM into M protein. Recent studies have suggested that prM protein might be implicated in the neurovirulence of ZIKV. Most vaccines targeting ZIKV include prM as the immunogen. Here, we review progress in our understanding of ZIKV prM protein and its application in ZIKV vaccine development.

Highlights

Zika virus (ZIKV) was first isolated in 1947 from a rhesus monkey taken from the Zika Forest in Uganda (Dick et al, 1952)
2018 Yuan et al, 2017; Bos et al, 2018 Zhu et al, 2016; Bos et al, 2018 Zhu et al, 2016; Bos et al, 2018 Wang et al, 2016; Zhu et al, 2016; Bos et al, 2018 Zhu et al, 2016; Bos et al, 2018 Bos et al, 2018 Bos et al, 2018 Bos et al, 2018 Bos et al, 2018 or pre-epidemic Asian wild type virus. These findings suggest that this serine to asparagine amino acid substitution in epidemic strains may have contributed to the recently observed congenital birth defects associated with ZIKV outbreaks in Brazil (Krauer et al, 2017)
Evolutionary and purifying selection pressures might have facilitated modifications of the ZIKV genome that enhance its replication efficiency and reduce host immune efficiency as it adapted to new hosts in urban environments

Summary

INTRODUCTION

Zika virus (ZIKV) was first isolated in 1947 from a rhesus monkey taken from the Zika Forest in Uganda (Dick et al, 1952). A recent genomic analysis of ZIKV strains revealed two amino acid substitutions in ZIKV prM protein isolated from strains contributing to epidemics in 2007 compared to that of a pre-epidemic Asian strain isolated in 1966 (Zhu et al, 2016). Another study found 10 amino acid substitutions between pre-epidemic and epidemic ZIKV prM proteins (Bos et al, 2018) (Table 1) These genomic variations might have been driven by ZIKV adopting an urban-based transmission cycle targeting humans as hosts rather than the original sylvatic mode of transmission that normally involves Aedes mosquitoes and non-human primates (Ramaiah et al, 2017). When human neural progenitor cells (hNPC) were infected with either the S139N or N139S mutant, the S139N mutant elicited more cell death than the N139S mutant

Amino acid position in ZIKV polyprotein

PERSPECTIVES FOR THE USE OF prM IN ZIKV VACCINE DEVELOPMENT

Reference for published results

CONCLUDING REMARKS