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A Reverse Mutation E143K within the PrM Protein of Zika Virus Asian Lineage Natal RGN Strain Increases Infectivity
Chen-Sheng Lin1, Wei-Jing Li2, Chih-Yi Liao2
1Division of Gastroenterology, Kuang Tien General Hospital, No. 117, Shatian Rd, Shalu District, Taichung 433, Taiwan.
Viruses
|July 27, 2022
Summary
Zika virus (ZIKV) Asian lineage replication is linked to specific amino acid changes. The Glu143Lys substitution enhances viral infectivity and replication, unlike wild-type ZIKV Asian strains.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Zika virus (ZIKV) Asian lineage outbreaks correlate with microcephaly and Guillain-Barré syndrome.
- Amino acid substitutions, particularly in the prM protein, may explain ZIKV lineage-specific phenotypes.
Purpose of the Study:
- To investigate the role of specific amino acid substitutions in ZIKV Asian lineage infectivity and cytopathogenicity.
- To characterize the virological properties of wild-type and mutant ZIKV Natal RGN strains.
Main Methods:
- Generated and characterized single-round infectious particles (SRIPs) and infectious clones (i.c.s) of ZIKV Asian-lineage Natal RGN.
- Analyzed mutations at positions 139 (Asn139→Ser139) and 143 (Glu143→Lys143) in ZIKV polyproteins.
- Assessed viral replication kinetics, infectivity, and cytopathic effects in human cell lines.
Main Results:
- The Glu143Lys (E143K) mutation significantly increased cytopathic effect, viral RNA/protein synthesis, and virus yield compared to wild-type and Asn139Ser (N139S) mutants.
- E143K mutant showed enhanced viral attachment, entry, intracellular/extracellular virion production, and E protein assembly near the plasma membrane.
- Lys143, a conserved residue in African lineages, is crucial for viral replication, attachment, entry, assembly, and egress.
Conclusions:
- The positively charged Lys143 residue enhances ZIKV replication kinetics and infectivity.
- The negatively charged Glu143 residue in ZIKV Asian lineage prM protein contributes to reduced replication efficiency, infectivity, and cytopathicity.
