Myxoma and vaccinia viruses bind differentially to human leukocytes

Winnie M. Chan, Eric C. Bartee, Jan S. Moreb, Ken Dower, John H. Connor, Douglas McFadden

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Myxoma virus (MYXV) and vaccinia virus (VACV), two distinct members of the family Poxviridae, are both currently being developed as oncolytic virotherapeutic agents. Recent studies have demonstrated that ex vivo treatment with MYXV can selectively recognize and kill contaminating cancerous cells from autologous bone marrow transplants without perturbing the engraftment of normal CD34+ hematopoietic stem and progenitor cells. However, the mechanism(s) by which MYXV specifically recognizes and eliminates the cancer cells in the autografts is not understood. While little is known about the cellular attachment factor(s) exploited by MYXV for entry into any target cells, VACV has been shown to utilize cell surface glycosaminoglycans such as heparan sulfate (HS), the extracellular matrix protein laminin, and/or integrin β1. We have constructed MYXV and VACV virions tagged with the Venus fluorescent protein and compared their characteristics of binding to various human cancer cell lines as well as to primary human leukocytes. We report that the binding of MYXV or VACV to some adherent cell lines could be partially inhibited by heparin, but laminin blocked only VACV binding. In contrast to cultured fibroblasts, the binding of MYXV and VACV to a wide spectrum of primary human leukocytes could not be competed by either HS or laminin. Additionally, MYXV and VACV exhibited very different binding characteristics against certain select human leukocytes, suggesting that the two poxviruses utilize different cell surface determinants for the attachment to these cells. These results indicate that VACV and MYXV can exhibit very different oncolytic tropisms against some cancerous human leukocytes.

Original languageEnglish (US)
Pages (from-to)4445-4460
Number of pages16
JournalJournal of Virology
Volume87
Issue number8
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

Fingerprint

Myxoma virus
Vaccinia virus
leukocytes
Leukocytes
laminin
Laminin
Poxviridae
Heparitin Sulfate
Hematopoietic Stem Cells
cells
Venus
cell lines
Virus Attachment
Cell Line
bone marrow transplant
Virus Internalization
tropisms
Tropism
Extracellular Matrix Proteins
glycosaminoglycans

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Chan, W. M., Bartee, E. C., Moreb, J. S., Dower, K., Connor, J. H., & McFadden, D. (2013). Myxoma and vaccinia viruses bind differentially to human leukocytes. Journal of Virology, 87(8), 4445-4460. https://doi.org/10.1128/JVI.03488-12

Myxoma and vaccinia viruses bind differentially to human leukocytes. / Chan, Winnie M.; Bartee, Eric C.; Moreb, Jan S.; Dower, Ken; Connor, John H.; McFadden, Douglas.

In: Journal of Virology, Vol. 87, No. 8, 01.04.2013, p. 4445-4460.

Research output: Contribution to journalArticle

Chan, WM, Bartee, EC, Moreb, JS, Dower, K, Connor, JH & McFadden, D 2013, 'Myxoma and vaccinia viruses bind differentially to human leukocytes', Journal of Virology, vol. 87, no. 8, pp. 4445-4460. https://doi.org/10.1128/JVI.03488-12
Chan, Winnie M. ; Bartee, Eric C. ; Moreb, Jan S. ; Dower, Ken ; Connor, John H. ; McFadden, Douglas. / Myxoma and vaccinia viruses bind differentially to human leukocytes. In: Journal of Virology. 2013 ; Vol. 87, No. 8. pp. 4445-4460.
@article{636cb82ffbd84387ab1fb7030a1c9911,
title = "Myxoma and vaccinia viruses bind differentially to human leukocytes",
abstract = "Myxoma virus (MYXV) and vaccinia virus (VACV), two distinct members of the family Poxviridae, are both currently being developed as oncolytic virotherapeutic agents. Recent studies have demonstrated that ex vivo treatment with MYXV can selectively recognize and kill contaminating cancerous cells from autologous bone marrow transplants without perturbing the engraftment of normal CD34+ hematopoietic stem and progenitor cells. However, the mechanism(s) by which MYXV specifically recognizes and eliminates the cancer cells in the autografts is not understood. While little is known about the cellular attachment factor(s) exploited by MYXV for entry into any target cells, VACV has been shown to utilize cell surface glycosaminoglycans such as heparan sulfate (HS), the extracellular matrix protein laminin, and/or integrin β1. We have constructed MYXV and VACV virions tagged with the Venus fluorescent protein and compared their characteristics of binding to various human cancer cell lines as well as to primary human leukocytes. We report that the binding of MYXV or VACV to some adherent cell lines could be partially inhibited by heparin, but laminin blocked only VACV binding. In contrast to cultured fibroblasts, the binding of MYXV and VACV to a wide spectrum of primary human leukocytes could not be competed by either HS or laminin. Additionally, MYXV and VACV exhibited very different binding characteristics against certain select human leukocytes, suggesting that the two poxviruses utilize different cell surface determinants for the attachment to these cells. These results indicate that VACV and MYXV can exhibit very different oncolytic tropisms against some cancerous human leukocytes.",
author = "Chan, {Winnie M.} and Bartee, {Eric C.} and Moreb, {Jan S.} and Ken Dower and Connor, {John H.} and Douglas McFadden",
year = "2013",
month = "4",
day = "1",
doi = "10.1128/JVI.03488-12",
language = "English (US)",
volume = "87",
pages = "4445--4460",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "8",

}

TY - JOUR

T1 - Myxoma and vaccinia viruses bind differentially to human leukocytes

AU - Chan, Winnie M.

AU - Bartee, Eric C.

AU - Moreb, Jan S.

AU - Dower, Ken

AU - Connor, John H.

AU - McFadden, Douglas

PY - 2013/4/1

Y1 - 2013/4/1

N2 - Myxoma virus (MYXV) and vaccinia virus (VACV), two distinct members of the family Poxviridae, are both currently being developed as oncolytic virotherapeutic agents. Recent studies have demonstrated that ex vivo treatment with MYXV can selectively recognize and kill contaminating cancerous cells from autologous bone marrow transplants without perturbing the engraftment of normal CD34+ hematopoietic stem and progenitor cells. However, the mechanism(s) by which MYXV specifically recognizes and eliminates the cancer cells in the autografts is not understood. While little is known about the cellular attachment factor(s) exploited by MYXV for entry into any target cells, VACV has been shown to utilize cell surface glycosaminoglycans such as heparan sulfate (HS), the extracellular matrix protein laminin, and/or integrin β1. We have constructed MYXV and VACV virions tagged with the Venus fluorescent protein and compared their characteristics of binding to various human cancer cell lines as well as to primary human leukocytes. We report that the binding of MYXV or VACV to some adherent cell lines could be partially inhibited by heparin, but laminin blocked only VACV binding. In contrast to cultured fibroblasts, the binding of MYXV and VACV to a wide spectrum of primary human leukocytes could not be competed by either HS or laminin. Additionally, MYXV and VACV exhibited very different binding characteristics against certain select human leukocytes, suggesting that the two poxviruses utilize different cell surface determinants for the attachment to these cells. These results indicate that VACV and MYXV can exhibit very different oncolytic tropisms against some cancerous human leukocytes.

AB - Myxoma virus (MYXV) and vaccinia virus (VACV), two distinct members of the family Poxviridae, are both currently being developed as oncolytic virotherapeutic agents. Recent studies have demonstrated that ex vivo treatment with MYXV can selectively recognize and kill contaminating cancerous cells from autologous bone marrow transplants without perturbing the engraftment of normal CD34+ hematopoietic stem and progenitor cells. However, the mechanism(s) by which MYXV specifically recognizes and eliminates the cancer cells in the autografts is not understood. While little is known about the cellular attachment factor(s) exploited by MYXV for entry into any target cells, VACV has been shown to utilize cell surface glycosaminoglycans such as heparan sulfate (HS), the extracellular matrix protein laminin, and/or integrin β1. We have constructed MYXV and VACV virions tagged with the Venus fluorescent protein and compared their characteristics of binding to various human cancer cell lines as well as to primary human leukocytes. We report that the binding of MYXV or VACV to some adherent cell lines could be partially inhibited by heparin, but laminin blocked only VACV binding. In contrast to cultured fibroblasts, the binding of MYXV and VACV to a wide spectrum of primary human leukocytes could not be competed by either HS or laminin. Additionally, MYXV and VACV exhibited very different binding characteristics against certain select human leukocytes, suggesting that the two poxviruses utilize different cell surface determinants for the attachment to these cells. These results indicate that VACV and MYXV can exhibit very different oncolytic tropisms against some cancerous human leukocytes.

UR - http://www.scopus.com/inward/record.url?scp=84875782674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875782674&partnerID=8YFLogxK

U2 - 10.1128/JVI.03488-12

DO - 10.1128/JVI.03488-12

M3 - Article

C2 - 23388707

AN - SCOPUS:84875782674

VL - 87

SP - 4445

EP - 4460

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 8

ER -