Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice

Nisha K. Duggal, Erin M. McDonald, James Weger-Lucarelli, Seth A. Hawks, Jana M. Ritter, Hannah Romo, Gregory D. Ebel, Aaron Brault

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Zika virus (ZIKV) infection can result in neurological disorders including Congenital Zika Syndrome in infants exposed to the virus in utero. Pregnant women can be infected by mosquito bite as well as by sexual transmission from infected men. Herein, the variants of ZIKV within the male reproductive tract and ejaculates were assessed in inoculated mice. We identified two non-synonymous variants at positions E-V330L and NS1-W98G. These variants were also present in the passage three PRVABC59 isolate and infectious clone relative to the patient serum PRVABC59 sequence. In subsequent studies, ZIKV E-330L was less pathogenic in mice than ZIKV E-330V as evident by increased average survival times. In Vero cells, ZIKV E-330L/NS1-98G outcompeted ZIKV E-330V/NS1-98W within 3 passages. These results suggest that the E-330L/NS1-98G variants are attenuating in mice and were enriched during cell culture passaging. Cell culture propagation of ZIKV could significantly affect animal model development and vaccine efficacy studies.

Original languageEnglish (US)
Pages (from-to)19-26
Number of pages8
JournalVirology
Volume530
DOIs
StatePublished - Apr 1 2019
Externally publishedYes

Fingerprint

Mutation
Cell Culture Techniques
Vero Cells
Bites and Stings
Nervous System Diseases
Culicidae
Zika Virus
Pregnant Women
Vaccines
Animal Models
Clone Cells
Viruses
Survival
Serum

Keywords

  • Flavivirus
  • Mouse model
  • Viral pathogenesis
  • Zika virus

ASJC Scopus subject areas

  • Virology

Cite this

Duggal, N. K., McDonald, E. M., Weger-Lucarelli, J., Hawks, S. A., Ritter, J. M., Romo, H., ... Brault, A. (2019). Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice. Virology, 530, 19-26. https://doi.org/10.1016/j.virol.2019.02.004

Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice. / Duggal, Nisha K.; McDonald, Erin M.; Weger-Lucarelli, James; Hawks, Seth A.; Ritter, Jana M.; Romo, Hannah; Ebel, Gregory D.; Brault, Aaron.

In: Virology, Vol. 530, 01.04.2019, p. 19-26.

Research output: Contribution to journalArticle

Duggal, NK, McDonald, EM, Weger-Lucarelli, J, Hawks, SA, Ritter, JM, Romo, H, Ebel, GD & Brault, A 2019, 'Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice', Virology, vol. 530, pp. 19-26. https://doi.org/10.1016/j.virol.2019.02.004
Duggal NK, McDonald EM, Weger-Lucarelli J, Hawks SA, Ritter JM, Romo H et al. Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice. Virology. 2019 Apr 1;530:19-26. https://doi.org/10.1016/j.virol.2019.02.004
Duggal, Nisha K. ; McDonald, Erin M. ; Weger-Lucarelli, James ; Hawks, Seth A. ; Ritter, Jana M. ; Romo, Hannah ; Ebel, Gregory D. ; Brault, Aaron. / Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice. In: Virology. 2019 ; Vol. 530. pp. 19-26.
@article{33a220eeba614e6b8d12d35a66c40d6f,
title = "Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice",
abstract = "Zika virus (ZIKV) infection can result in neurological disorders including Congenital Zika Syndrome in infants exposed to the virus in utero. Pregnant women can be infected by mosquito bite as well as by sexual transmission from infected men. Herein, the variants of ZIKV within the male reproductive tract and ejaculates were assessed in inoculated mice. We identified two non-synonymous variants at positions E-V330L and NS1-W98G. These variants were also present in the passage three PRVABC59 isolate and infectious clone relative to the patient serum PRVABC59 sequence. In subsequent studies, ZIKV E-330L was less pathogenic in mice than ZIKV E-330V as evident by increased average survival times. In Vero cells, ZIKV E-330L/NS1-98G outcompeted ZIKV E-330V/NS1-98W within 3 passages. These results suggest that the E-330L/NS1-98G variants are attenuating in mice and were enriched during cell culture passaging. Cell culture propagation of ZIKV could significantly affect animal model development and vaccine efficacy studies.",
keywords = "Flavivirus, Mouse model, Viral pathogenesis, Zika virus",
author = "Duggal, {Nisha K.} and McDonald, {Erin M.} and James Weger-Lucarelli and Hawks, {Seth A.} and Ritter, {Jana M.} and Hannah Romo and Ebel, {Gregory D.} and Aaron Brault",
year = "2019",
month = "4",
day = "1",
doi = "10.1016/j.virol.2019.02.004",
language = "English (US)",
volume = "530",
pages = "19--26",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice

AU - Duggal, Nisha K.

AU - McDonald, Erin M.

AU - Weger-Lucarelli, James

AU - Hawks, Seth A.

AU - Ritter, Jana M.

AU - Romo, Hannah

AU - Ebel, Gregory D.

AU - Brault, Aaron

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Zika virus (ZIKV) infection can result in neurological disorders including Congenital Zika Syndrome in infants exposed to the virus in utero. Pregnant women can be infected by mosquito bite as well as by sexual transmission from infected men. Herein, the variants of ZIKV within the male reproductive tract and ejaculates were assessed in inoculated mice. We identified two non-synonymous variants at positions E-V330L and NS1-W98G. These variants were also present in the passage three PRVABC59 isolate and infectious clone relative to the patient serum PRVABC59 sequence. In subsequent studies, ZIKV E-330L was less pathogenic in mice than ZIKV E-330V as evident by increased average survival times. In Vero cells, ZIKV E-330L/NS1-98G outcompeted ZIKV E-330V/NS1-98W within 3 passages. These results suggest that the E-330L/NS1-98G variants are attenuating in mice and were enriched during cell culture passaging. Cell culture propagation of ZIKV could significantly affect animal model development and vaccine efficacy studies.

AB - Zika virus (ZIKV) infection can result in neurological disorders including Congenital Zika Syndrome in infants exposed to the virus in utero. Pregnant women can be infected by mosquito bite as well as by sexual transmission from infected men. Herein, the variants of ZIKV within the male reproductive tract and ejaculates were assessed in inoculated mice. We identified two non-synonymous variants at positions E-V330L and NS1-W98G. These variants were also present in the passage three PRVABC59 isolate and infectious clone relative to the patient serum PRVABC59 sequence. In subsequent studies, ZIKV E-330L was less pathogenic in mice than ZIKV E-330V as evident by increased average survival times. In Vero cells, ZIKV E-330L/NS1-98G outcompeted ZIKV E-330V/NS1-98W within 3 passages. These results suggest that the E-330L/NS1-98G variants are attenuating in mice and were enriched during cell culture passaging. Cell culture propagation of ZIKV could significantly affect animal model development and vaccine efficacy studies.

KW - Flavivirus

KW - Mouse model

KW - Viral pathogenesis

KW - Zika virus

UR - http://www.scopus.com/inward/record.url?scp=85061668937&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061668937&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2019.02.004

DO - 10.1016/j.virol.2019.02.004

M3 - Article

VL - 530

SP - 19

EP - 26

JO - Virology

JF - Virology

SN - 0042-6822

ER -