Identification of genetic determinants of a tick-borne flavivirus associated with host-specific adaptation and pathogenicity.

Abstract:

:Tick-borne flaviviruses are maintained in nature in an enzootic cycle involving a tick vector and a vertebrate host. Thus, the virus replicates in two disparate hosts, each providing selective pressures that can influence virus replication and pathogenicity. To identify viral determinants associated with replication in the individual hosts, plaque purified Langat virus (TP21pp) was adapted to growth in mouse or tick cell lines to generate two virus variants, MNBp20 and ISEp20, respectively. Virus adaptation to mouse cells resulted in four amino acid changes in MNBp20 relative to TP21pp, occurring in E, NS4A and NS4B. A comparison between TP21pp and ISEp20 revealed three amino acid modifications in M, NS3 and NS4A of ISEp20. ISEp20, but not MNBp20, was attenuated following intraperitoneal inoculation of mice. Following isolation from mice brains, additional mutations reproducibly emerged in E and NS3 of ISEp20 that were possibly compensatory for the initial adaptation to tick cells. Thus, our data implicate a role for E, M, NS3, NS4A and NS4B in host adaptation and pathogenicity of tick-borne flaviviruses.

journal_name

Virology

journal_title

Virology

authors

Mitzel DN,Best SM,Masnick MF,Porcella SF,Wolfinbarger JB,Bloom ME

doi

10.1016/j.virol.2008.08.030

subject

Has Abstract

pub_date

2008-11-25 00:00:00

pages

268-76

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(08)00557-6

journal_volume

381

pub_type

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