Table 4.

ZIKV proteins and associated cytopathic effects.

Protein	Primary Function	Main Phenotypes	References
Structural Proteins
anaC	Anchored capsid protein	In the fission yeast cells, it restricts cellular growth and affects cell cycling. It also induces cellular oxidative stress leading to cell death.	[9]
C	Capsid protein	In the fission yeast cells, it restricts cellular growth. It also induces cellular oxidative stress leading to cell death; in hNPCs, it induces ribosomal stress and apoptosis.	[9,130]
prM	Precursor membrane protein	In the fission yeast cells, it restricts cellular growth and affects cell cycling. It also induces cellular oxidative stress and autophagy leading to cell death; a single prM mutation contributes to fetal microcephaly	[9,131]
M	Membrane protein	In the fission yeast cells, it restricts cellular growth and affects cell cycling. It also induces cellular oxidative stress and autophagy, leading to cell death.	[9]
Pr	Cleaved product from prM	Unknown
E	Envelope protein	A putative cytopathic factor based on a yeast study. E protein facilitates viral entry. A single residue in the αB helix of the E protein is critical for Zika virus thermostability, and interaction with the host cell membrane.	[9,132]
Non-structural Proteins
NS1	Viral replication, pathogenesis and immune evasion	In the fission yeast cells, it induces cellular oxidative stress and autophagy leading to cell death; An essential role in viral replication and immune evasion. It presents on the cell surface and presents as a dimer within cells, and as a hexamer once being secreted. NS1-mediated CPEs in mammalian cells have not yet been established.	[47,48,49,133]
NS2A	Unknown	In the fission yeast cells, it induces cellular oxidative stress and autophagy leading to cell death; ZIKV-encoded NS2A disrupts mammalian cortical neurogenesis by degrading adherens junction (AJ) proteins, leading to reduced proliferation and premature differentiation of radial glial cells and aberrant positioning of newborn neurons.	[131]
NS2B	Protease cofactor	In fission yeast cells, it restricts cellular growth. Forms a protease complex with NS3; a putative cytopathic factor based on a yeast study	[9,134]
NS3	Protease and helicase	NS3-mediated CPEs in mammalian cells have not yet been established.	[131]
NS4A	Viral RNA synthesis and viral morphogenesis	In the fission yeast cells, it restricts cellular growth and affects cell cycling. It also induces cellular oxidative stress and autophagy leading to cell death. It induces autophagy by inhibiting Atk-mediated TOR pathway through Tor1/TSC1 and Tip41 in both yeast and mammalian cells.	[9,111]
2K	A signal peptide	Viral RNA synthesis and viral morphogenesis. 2K-mediated CPEs have not yet been established.	[9,11,12]
NS4B	Viral RNA synthesis and viral morphogenesis	Synergistic to NS4A on inhibiting Akt-mediated TOR pathway	[111]
NS5	Methyltrasferase; RNA-dependent polymerase	NS5-mediated CPEs in mammalian cells have not yet been established.	[128]