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Title: Comparative genomics, infectivity and cytopathogenicity of Zika viruses produced by acutely and persistently infected human hematopoietic cell lines

Abstract

Zika virus (ZIKV), an arthropod-borne virus, has emerged as a major human pathogen. Prolonged or persistent ZIKV infection of human cells and tissues may serve as a reservoir for the virus and present serious challenges to the safety of public health. Human hematopoietic cell lines with different developmental properties revealed differences in susceptibility and outcomes to ZIKV infection. In three separate studies involving the prototypic MR 766 ZIKV strain and the human monocytic leukemia U937 cell line, ZIKV initially developed only a low-grade infection at a slow rate. After continuous culture for several months, persistently ZIKV-infected cell lines were observed with most, if not all, cells testing positive for ZIKV antigen. The infected cultures produced ZIKV RNA (v-RNA) and infectious ZIKVs persistently (“persistent ZIKVs”) with distinct infectivity and pathogenicity when tested using various kinds of host cells. When the genomes of ZIKVs from the three persistently infected cell lines were compared with the genome of the prototypic MR 766 ZIKV strain, distinct sets of mutations specific to each cell line were found. Significantly, all three “persistent ZIKVs” were capable of infecting fresh U937 cells with high efficiency at rapid rates, resulting in the development of a new set of persistentlymore » ZIKV-infected U937 cell lines. The genomes of ZIKVs from the new set of persistently ZIKV-infected U937 cell lines were further analyzed for their different mutations. The 2nd generation of persistent ZIKVs continued to possess most of the distinct sets of mutations specific to the respective 1st generation of persistent ZIKVs. We anticipate that the study will contribute to the understanding of the fundamental biology of adaptive mutations and selection during viral persistence. The persistently ZIKVinfected human cell lines that we developed will also be useful to investigate critical molecular pathways of ZIKV persistence and to study drugs or countermeasures against ZIKV infections and transmission.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [1]; ORCiD logo [1];  [2]; ORCiD logo [1]
  1. U.S. Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Biologics Evaluation and Research. Office of Tissues and Advanced Therapies. Division of Cellular and Gene Therapies. Tissue Microbiology Lab.
  2. U.S. Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Biologics Evaluation and Research. Office of Vaccines Research and Review. Division of Viral Products. Lab of Pediatric and Respiratory Viral Diseases
Publication Date:
Research Org.:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1627866
Grant/Contract Number:  
SC0014664
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 13; Journal Issue: 9; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Science & Technology - Other Topics

Citation Formats

Li, Bingjie, Liao, Hsiao-Mei, Liu, Hebing, Tsai, Shien, Zhang, Jing, Hung, Guo-Chiuan, Chin, Pei-Ju, Gao, Yamei, and Lo, Shyh-Ching. Comparative genomics, infectivity and cytopathogenicity of Zika viruses produced by acutely and persistently infected human hematopoietic cell lines. United States: N. p., 2018. Web. doi:10.1371/journal.pone.0203331.
Li, Bingjie, Liao, Hsiao-Mei, Liu, Hebing, Tsai, Shien, Zhang, Jing, Hung, Guo-Chiuan, Chin, Pei-Ju, Gao, Yamei, & Lo, Shyh-Ching. Comparative genomics, infectivity and cytopathogenicity of Zika viruses produced by acutely and persistently infected human hematopoietic cell lines. United States. https://doi.org/10.1371/journal.pone.0203331
Li, Bingjie, Liao, Hsiao-Mei, Liu, Hebing, Tsai, Shien, Zhang, Jing, Hung, Guo-Chiuan, Chin, Pei-Ju, Gao, Yamei, and Lo, Shyh-Ching. Fri . "Comparative genomics, infectivity and cytopathogenicity of Zika viruses produced by acutely and persistently infected human hematopoietic cell lines". United States. https://doi.org/10.1371/journal.pone.0203331. https://www.osti.gov/servlets/purl/1627866.
@article{osti_1627866,
title = {Comparative genomics, infectivity and cytopathogenicity of Zika viruses produced by acutely and persistently infected human hematopoietic cell lines},
author = {Li, Bingjie and Liao, Hsiao-Mei and Liu, Hebing and Tsai, Shien and Zhang, Jing and Hung, Guo-Chiuan and Chin, Pei-Ju and Gao, Yamei and Lo, Shyh-Ching},
abstractNote = {Zika virus (ZIKV), an arthropod-borne virus, has emerged as a major human pathogen. Prolonged or persistent ZIKV infection of human cells and tissues may serve as a reservoir for the virus and present serious challenges to the safety of public health. Human hematopoietic cell lines with different developmental properties revealed differences in susceptibility and outcomes to ZIKV infection. In three separate studies involving the prototypic MR 766 ZIKV strain and the human monocytic leukemia U937 cell line, ZIKV initially developed only a low-grade infection at a slow rate. After continuous culture for several months, persistently ZIKV-infected cell lines were observed with most, if not all, cells testing positive for ZIKV antigen. The infected cultures produced ZIKV RNA (v-RNA) and infectious ZIKVs persistently (“persistent ZIKVs”) with distinct infectivity and pathogenicity when tested using various kinds of host cells. When the genomes of ZIKVs from the three persistently infected cell lines were compared with the genome of the prototypic MR 766 ZIKV strain, distinct sets of mutations specific to each cell line were found. Significantly, all three “persistent ZIKVs” were capable of infecting fresh U937 cells with high efficiency at rapid rates, resulting in the development of a new set of persistently ZIKV-infected U937 cell lines. The genomes of ZIKVs from the new set of persistently ZIKV-infected U937 cell lines were further analyzed for their different mutations. The 2nd generation of persistent ZIKVs continued to possess most of the distinct sets of mutations specific to the respective 1st generation of persistent ZIKVs. We anticipate that the study will contribute to the understanding of the fundamental biology of adaptive mutations and selection during viral persistence. The persistently ZIKVinfected human cell lines that we developed will also be useful to investigate critical molecular pathways of ZIKV persistence and to study drugs or countermeasures against ZIKV infections and transmission.},
doi = {10.1371/journal.pone.0203331},
journal = {PLoS ONE},
number = 9,
volume = 13,
place = {United States},
year = {Fri Sep 07 00:00:00 EDT 2018},
month = {Fri Sep 07 00:00:00 EDT 2018}
}

Works referenced in this record:

Detection of RNA from a Novel West Nile-like Virus and High Prevalence of an Insect-specific Flavivirus in Mosquitoes in the Yucatan Peninsula of Mexico
journal, January 2009

  • Bartholomay, Lyric C.; Lanciotti, Robert S.; Lin, Ming
  • The American Journal of Tropical Medicine and Hygiene, Vol. 80, Issue 1
  • DOI: 10.4269/ajtmh.2009.80.85

Zika Virus Strains Potentially Display Different Infectious Profiles in Human Neural Cells
journal, October 2016


Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs
journal, January 2016

  • Chan, Jasper Fuk-Woo; Yip, Cyril Chik-Yan; Tsang, Jessica Oi-Ling
  • Emerging Microbes & Infections, Vol. 5, Issue 1
  • DOI: 10.1038/emi.2016.99

Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells
journal, October 2017

  • Devhare, Pradip; Meyer, Keith; Steele, Robert
  • Cell Death & Disease, Vol. 8, Issue 10
  • DOI: 10.1038/cddis.2017.517

Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues
journal, March 2017


A diagnostic polymerase chain reaction assay for Zika virus
journal, July 2012

  • Balm, Michelle N. D.; Lee, Chun Kiat; Lee, Hong Kai
  • Journal of Medical Virology, Vol. 84, Issue 9
  • DOI: 10.1002/jmv.23241

Blocking Zika virus vertical transmission
journal, January 2018


Dengue Virus Type 2 Infections of Aedes aegypti Are Modulated by the Mosquito's RNA Interference Pathway
journal, February 2009


Lysozyme synthesis by established human and murine histiocytic lymphoma cell lines.
journal, June 1976

  • Ralph, P.; Moore, M. A.; Nilsson, K.
  • Journal of Experimental Medicine, Vol. 143, Issue 6
  • DOI: 10.1084/jem.143.6.1528

Evaluation of a field-deployable reverse transcription-insulated isothermal PCR for rapid and sensitive on-site detection of Zika virus
journal, December 2017


Transmission of West Nile Virus from an Organ Donor to Four Transplant Recipients
journal, May 2003

  • Iwamoto, Martha; Jernigan, Daniel B.; Guasch, Antonio
  • New England Journal of Medicine, Vol. 348, Issue 22
  • DOI: 10.1056/NEJMoa022987

Detection of Zika virus in saliva
journal, July 2015


Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears
journal, September 2016


Mycoplasma fermentans infection promotes immortalization of human peripheral blood mononuclear cells in culture
journal, December 2004


CD14+CD16+ monocytes are the main target of Zika virus infection in peripheral blood mononuclear cells in a paediatric study in Nicaragua
journal, October 2017


The FDA-approved drug sofosbuvir inhibits Zika virus infection
journal, January 2017


Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys
journal, May 2017


Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques
journal, January 2017


Possible Association Between Zika Virus Infection and Microcephaly — Brazil, 2015
journal, January 2016

  • Schuler-Faccini, Lavinia; Ribeiro, Erlane M.; Feitosa, Ian M. L.
  • MMWR. Morbidity and Mortality Weekly Report, Vol. 65, Issue 3
  • DOI: 10.15585/mmwr.mm6503e2

Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses
journal, January 2007


A single mutation in the prM protein of Zika virus contributes to fetal microcephaly
journal, September 2017


A Hamster-Derived West Nile Virus Isolate Induces Persistent Renal Infection in Mice
journal, June 2013


Zika Virus: Medical Countermeasure Development Challenges
journal, March 2016


Detection of Zika Virus in Urine
journal, January 2015

  • Gourinat, Ann-Claire; O’Connor, Olivia; Calvez, Elodie
  • Emerging Infectious Diseases, Vol. 21, Issue 1
  • DOI: 10.3201/eid2101.140894

Suggested mechanisms for Zika virus causing microcephaly: what do the genomes tell us?
journal, December 2017


Nucleotide and Amino acid Changes in west nile Virus Strains Exhibiting Renal Tropism in Hamsters
journal, October 2005

  • Yang, Zhanqiu; Siirin, Marina; Tesh, Robert B.
  • The American Journal of Tropical Medicine and Hygiene, Vol. 73, Issue 4
  • DOI: 10.4269/ajtmh.2005.73.803

Niclosamide rescues microcephaly in a humanized in vivo model of Zika infection using human induced neural stem cells
journal, January 2018

  • Cairns, Dana M.; Boorgu, Devi Sai Sri Kavya; Levin, Michael
  • Biology Open, Vol. 7, Issue 1
  • DOI: 10.1242/bio.031807

Possible Association Between Zika Virus Infection and Microcephaly — Brazil, 2015
journal, January 2016

  • Schuler-Faccini, Lavinia; Ribeiro, Erlane M.; Feitosa, Ian M. L.
  • MMWR. Morbidity and Mortality Weekly Report, Vol. 65, Issue 3
  • DOI: 10.15585/mmwr.mm6503e2er

Transmission of West Nile virus by organ transplantation
journal, January 2005

  • Kusne, Shimon; Smilack, Jerry
  • Liver Transplantation, Vol. 11, Issue 2
  • DOI: 10.1002/lt.20350

Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses
journal, January 2007


Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys
journal, May 2017


Zika Virus Infection in Mice Causes Panuveitis with Shedding of Virus in Tears
journal, September 2016


Zika Virus Strains Potentially Display Different Infectious Profiles in Human Neural Cells
journal, October 2016


Detection of Zika virus in saliva
journal, July 2015


A positively selected mutation in the WNV 2K peptide confers resistance to superinfection exclusion in vivo
journal, September 2014


Zika virus and microcephaly: why is this situation a PHEIC?
journal, February 2016


Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells
journal, October 2017

  • Devhare, Pradip; Meyer, Keith; Steele, Robert
  • Cell Death & Disease, Vol. 8, Issue 10
  • DOI: 10.1038/cddis.2017.517

Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs
journal, January 2016

  • Chan, Jasper Fuk-Woo; Yip, Cyril Chik-Yan; Tsang, Jessica Oi-Ling
  • Emerging Microbes & Infections, Vol. 5, Issue 1
  • DOI: 10.1038/emi.2016.99

Zika virus targets blood monocytes
journal, October 2017


Blocking Zika virus vertical transmission
journal, January 2018


Zika Virus and Microcephaly
journal, March 2016

  • Rubin, Eric J.; Greene, Michael F.; Baden, Lindsey R.
  • New England Journal of Medicine, Vol. 374, Issue 10
  • DOI: 10.1056/nejme1601862

Lysozyme synthesis by established human and murine histiocytic lymphoma cell lines.
journal, June 1976

  • Ralph, P.; Moore, M. A.; Nilsson, K.
  • Journal of Experimental Medicine, Vol. 143, Issue 6
  • DOI: 10.1084/jem.143.6.1528

Laboratory Evaluation of Commercially Available Platforms to Detect West Nile and Zika Viruses From Honey Cards
journal, February 2018

  • Burkhalter, Kristen L.; Wiggins, Keenan; Burkett-Cadena, Nathan
  • Journal of Medical Entomology, Vol. 55, Issue 3
  • DOI: 10.1093/jme/tjy005

Zika Virus can Persist in Body Fluids for Prolonged Periods
journal, June 2017


A single mutation in the prM protein of Zika virus contributes to fetal microcephaly
journal, September 2017


Mycoplasma fermentans infection promotes immortalization of human peripheral blood mononuclear cells in culture
journal, December 2004


Suggested mechanisms for Zika virus causing microcephaly: what do the genomes tell us?
journal, December 2017


Niclosamide rescues microcephaly in a humanized in vivo model of Zika infection using human induced neural stem cells
journal, January 2018

  • Cairns, Dana M.; Boorgu, Devi Sai Sri Kavya; Levin, Michael
  • Biology Open, Vol. 7, Issue 1
  • DOI: 10.1242/bio.031807

A Hamster-Derived West Nile Virus Isolate Induces Persistent Renal Infection in Mice
journal, June 2013


Zika Virus: Medical Countermeasure Development Challenges
journal, March 2016


Dengue Virus Type 2 Infections of Aedes aegypti Are Modulated by the Mosquito's RNA Interference Pathway
journal, February 2009


Possible Association Between Zika Virus Infection and Microcephaly — Brazil, 2015
journal, January 2016

  • Schuler-Faccini, Lavinia; Ribeiro, Erlane M.; Feitosa, Ian M. L.
  • MMWR. Morbidity and Mortality Weekly Report, Vol. 65, Issue 3
  • DOI: 10.15585/mmwr.mm6503e2

Detection of Zika Virus in Urine
journal, January 2015

  • Gourinat, Ann-Claire; O’Connor, Olivia; Calvez, Elodie
  • Emerging Infectious Diseases, Vol. 21, Issue 1
  • DOI: 10.3201/eid2101.140894

Nucleotide and Amino acid Changes in west nile Virus Strains Exhibiting Renal Tropism in Hamsters
journal, October 2005

  • Yang, Zhanqiu; Siirin, Marina; Tesh, Robert B.
  • The American Journal of Tropical Medicine and Hygiene, Vol. 73, Issue 4
  • DOI: 10.4269/ajtmh.2005.73.803