Success of measles virotherapy in ATL depends on type I interferon secretion and responsiveness

M. Cecilia M. Parrula, Soledad A. Fernandez, Kristina Landes, Devra Huey, Michael Dale Lairmore, Stefan Niewiesk

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Adult T cell leukemia/lymphoma (ATL) is a highly aggressive CD4+/CD25+ T-cell malignancy caused by human T cell lymphotropic virus type 1 (HTLV-1). Previous studies in the MET-1 cell/NOD/SCID mouse model of ATL demonstrated that MET-1 cells are very susceptible to measles virus (MV) oncolytic therapy. To further evaluate the potential of MV therapy in ATL, the susceptibility of several HTLV-1 transformed CD4+ T cell lines (MT-1, MT-2, MT-4 and C8166-45) as well as HTLV-1 negative CD4+ T cell lines (Jurkat and CCRF-CEM) to infection with MV was tested in vitro. All cell lines were permissive to MV infection and subsequent cell death, except MT-1 and CCRF-CEM cells which were susceptible and permissive to MV infection, but resistant to cell death. The resistance to MV-mediated cell death was associated with IFNβ produced by MT-1 and CCRF-CEM cells. Inhibition of IFNβ rendered MT-1 and CCRF-CEM cells susceptible to MV-mediated cell death. Cells susceptible to MV-induced cell death did not produce nor were responsive to IFNβ. Upon infection with Newcastle Disease Virus (NDV), MT-1 and CCRF-CEM but not the susceptible cell lines up-regulated pSTAT-2. In vivo, treatment of tumors induced by MT-1 cell lines which produce IFNβ demonstrated only small increases in mean survival time, while only two treatments prolonged mean survival time in mice with MET-1 tumors deficient in type I interferon production. These results indicate that type I interferon production is closely linked with the inability of tumor cells to respond to type I interferon. Screening of tumor cells for type I interferon could be a useful strategy to select candidate patients for MV virotherapy.

Original languageEnglish (US)
Pages (from-to)206-213
Number of pages8
JournalVirus Research
Volume189
DOIs
StatePublished - Aug 30 2014
Externally publishedYes

Fingerprint

Adult T Cell Leukemia Lymphoma
Interferon Type I
Measles virus
Measles
Cell Death
T-Lymphocytes
Human T-lymphotropic virus 1
Cell Line
Virus Diseases
Neoplasms
Survival Rate
Newcastle disease virus
Inbred NOD Mouse
SCID Mice
Therapeutics
Infection

Keywords

  • HTLV
  • Leukemia
  • Lymphoma
  • Measles virus
  • Mouse model
  • Virotherapy

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Cancer Research

Cite this

Success of measles virotherapy in ATL depends on type I interferon secretion and responsiveness. / M. Parrula, M. Cecilia; Fernandez, Soledad A.; Landes, Kristina; Huey, Devra; Lairmore, Michael Dale; Niewiesk, Stefan.

In: Virus Research, Vol. 189, 30.08.2014, p. 206-213.

Research output: Contribution to journalArticle

M. Parrula, M. Cecilia ; Fernandez, Soledad A. ; Landes, Kristina ; Huey, Devra ; Lairmore, Michael Dale ; Niewiesk, Stefan. / Success of measles virotherapy in ATL depends on type I interferon secretion and responsiveness. In: Virus Research. 2014 ; Vol. 189. pp. 206-213.
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AU - Lairmore, Michael Dale

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