ArticlePLoS pathogens2021
Neuroinvasiveness of the MR766 strain of Zika virus in IFNAR-/- mice maps to prM residues conserved amongst African genotype viruses.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 28 citations in OpenAlex.
- Type I IFN coordinates resistance and tolerance against Zika virus disease by inducing NK cell recruitment and limiting neutrophil-driven neuropathology in the brain.Brain, behavior, & immunity - health · 2026Article
- Bioinformatics-Guided structural characterization and immunogenicity assessment of multi-epitope vaccine candidates against Zika virus.Journal, genetic engineering & biotechnology · 2026Article
- Virus-like particle vaccine with authentic quaternary epitopes protects against Zika virus-induced viremia and testicular damage.Journal of virology · 2025Article
- Identification of antiviral RNAi regulators, ILF3/DHX9, recruit at ZIKV stem loop B to protect against ZIKV induced microcephaly.Nature communications · 2025Article
- Evolution of Zika virus inVirus evolution · 2025Article
- A chimeric vaccine derived from Australian genotype IV Japanese encephalitis virus protects mice from lethal challenge.NPJ vaccines · 2024Article
- Subgenomic flavivirus RNA as key target for live-attenuated vaccine development.Journal of virology · 2024Review
- Replication properties of a contemporary Zika virus from West Africa.PLoS neglected tropical diseases · 2024Article
- Characterisation of a Japanese Encephalitis virus genotype 4 isolate from the 2022 Australian outbreak.Npj viruses · 2024Article
- The Drosophila melanogaster prophenoloxidase system participates in immunity against Zika virus infection.European journal of immunology · 2023Article
- Asian Zika virus can acquire generic African-lineage mutations duringEmerging microbes & infections · 2023Article
- Zika virus prM protein contains cholesterol binding motifs required for virus entry and assembly.Nature communications · 2023Article
- A single amino acid substitution in the capsid protein of Zika virus contributes to a neurovirulent phenotype.Nature communications · 2023Article
- ZIKV Strains Elicit Different Inflammatory and Anti-Viral Responses in Microglia Cells.Viruses · 2023Article
- Key Residue in the Precursor Region of M Protein Contributes to the Neurovirulence and Neuroinvasiveness of the African Lineage of Zika Virus.Journal of virology · 2023Article
- Comparative Efficacy of Mayaro Virus-Like Particle Vaccines Produced in Insect or Mammalian Cells.Journal of virology · 2023Article
- Review
- Influence of Zika virus 3'-end sequence and nonstructural protein evolution on the viral replication competence and virulence.Emerging microbes & infections · 2022Article
- Article
- Zika M-A Potential Viroporin: Mutational Study and Drug Repurposing.Biomedicines · 2022Article
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zika virus (ZIKV) strains are classified into the African and Asian genotypes. The higher virulence of the African MR766 strain, which has been used extensively in ZIKV research, in adult IFNα/β receptor knockout (IFNAR-/-) mice is widely viewed as an artifact associated with mouse adaptation due to at least 146 passages in wild-type suckling mouse brains. To gain insights into the molecular determinants of MR766's virulence, a series of genes from MR766 were swapped with those from the Asian genotype PRVABC59 isolate, which is less virulent in IFNAR-/- mice. MR766 causes 100% lethal infection in IFNAR-/- mice, but when the prM gene of MR766 was replaced with that of PRVABC59, the chimera MR/PR(prM) showed 0% lethal infection. The reduced virulence was associated with reduced neuroinvasiveness, with MR766 brain titers ≈3 logs higher than those of MR/PR(prM) after subcutaneous infection, but was not significantly different in brain titers of MR766 and MR/PR(prM) after intracranial inoculation. MR/PR(prM) also showed reduced transcytosis when compared with MR766 in vitro. The high neuroinvasiveness of MR766 in IFNAR-/- mice could be linked to the 10 amino acids that differ between the prM proteins of MR766 and PRVABC59, with 5 of these changes affecting positive charge and hydrophobicity on the exposed surface of the prM protein. These 10 amino acids are highly conserved amongst African ZIKV isolates, irrespective of suckling mouse passage, arguing that the high virulence of MR766 in adult IFNAR-/- mice is not the result of mouse adaptation.
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