Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus that causes febrile illness. The recent spread of ZIKV from Asia to the Americas via the Pacific region has revealed unprecedented features of ZIKV, including transplacental congenital infection causing microcephaly. Amino acid changes have been hypothesized to underlie the spread and novel features of American ZIKV strains; however, the relationship between genetic changes and the epidemic remains controversial. A comparison of the characteristics of a Southeast Asian strain (NIID123) and an American strain (PRVABC59) revealed that the latter had a higher replication ability in cultured cells and higher virulence in mice. In this study, we aimed to identify the genetic region of ZIKV responsible for these different characteristics using reverse genetics. A chimeric NIID123 strain in which the E protein was replaced with that of PRVABC59 showed a lower growth ability than the recombinant wild-type strain. Adaptation of the chimeric NIID123 to Vero cells induced a Phe-to-Leu amino acid substitution at position 146 of the prM protein; PRVABC59 also has Leu at this position. Leu at this position was found to be responsible for the viral replication ability and partially, for the pathogenicity in mouse testes.
Highlights
Zika virus (ZIKV) is a mosquito-borne flavivirus that causes febrile illness
These findings indicated that genetic differences between PRVABC59 and NIID123 are involved in the replication ability and pathogenicity of the viruses
RNIID123 prMF146L G (Leu) G (Arg) A (Asn) G (Val) U (Ser) Extrapolated*. Based on their amino acid sequences, Asian/American-lineage ZIKV strains are classified into Southeast Asian, Pacific, and American s ubtypes[33,34]
Summary
The recent spread of ZIKV from Asia to the Americas via the Pacific region has revealed unprecedented features of ZIKV, including transplacental congenital infection causing microcephaly. Adaptation of the chimeric NIID123 to Vero cells induced a Phe-to-Leu amino acid substitution at position 146 of the prM protein; PRVABC59 has Leu at this position Leu at this position was found to be responsible for the viral replication ability and partially, for the pathogenicity in mouse testes. Mice inoculated with PRVABC59 often showed testicular atrophy and scarring, whereas no testis damage was seen in mice inoculated with NIID123 at 6 weeks post infection[34] These findings indicated that genetic differences between PRVABC59 and NIID123 are involved in the replication ability and pathogenicity of the viruses
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