In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 7 ( 2021-7-26), p. e1009788-
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009788
DOI:
10.1371/journal.ppat.1009788.g001
DOI:
10.1371/journal.ppat.1009788.g002
DOI:
10.1371/journal.ppat.1009788.g003
DOI:
10.1371/journal.ppat.1009788.g004
DOI:
10.1371/journal.ppat.1009788.g005
DOI:
10.1371/journal.ppat.1009788.g006
DOI:
10.1371/journal.ppat.1009788.g007
DOI:
10.1371/journal.ppat.1009788.t001
DOI:
10.1371/journal.ppat.1009788.s001
DOI:
10.1371/journal.ppat.1009788.s002
DOI:
10.1371/journal.ppat.1009788.s003
DOI:
10.1371/journal.ppat.1009788.s004
DOI:
10.1371/journal.ppat.1009788.s005
DOI:
10.1371/journal.ppat.1009788.s006
DOI:
10.1371/journal.ppat.1009788.s007
DOI:
10.1371/journal.ppat.1009788.s008
DOI:
10.1371/journal.ppat.1009788.s009
DOI:
10.1371/journal.ppat.1009788.s010
DOI:
10.1371/journal.ppat.1009788.s011
DOI:
10.1371/journal.ppat.1009788.s012
DOI:
10.1371/journal.ppat.1009788.s013
DOI:
10.1371/journal.ppat.1009788.s014
DOI:
10.1371/journal.ppat.1009788.s015
DOI:
10.1371/journal.ppat.1009788.s016
DOI:
10.1371/journal.ppat.1009788.s017
DOI:
10.1371/journal.ppat.1009788.s018
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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