Frequent detection of infectious xenotropic murine leukemia virus (XMLV) in human cultures established from mouse xenografts

Yu An Zhang, Anirban Maitra, Jer Tsong Hsieh, Charles M. Rudin, Craig D. Peacock, Collins Karikari, Rolf A. Brekken, Victor Stastny, Boning Gao, Luc Girard, Ignacio Wistuba, Eugene Frenkel, John D. Minna, Adi F. Gazdar

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Purpose: To investigate the frequency of xenotropic murine leukemia virus (MLV) presence in human cell lines established from mouse xenografts and to search for the evidence of horizontal viral spread to other cell lines. Results: Six of 23 (26%) mouse DNA free xenograft cultures were strongly positive for MLV and their sequences had greater than 99% homology to known MLV strains. Four of five available supernatant fluids from these viral positive cultures were strongly positive for RT activity. Three of these supernatant fluids were studied to confirm the infectivity of the released virions for other human culture cells. Of the 78 non-xenograft derived cell lines maintained in the xenograft culture-containing facilities, 13 (17%) were positive for MLV, including XMRV, a virus strain first identified in human tissues. By contrast, all 50 cultures maintained in a xenograft culture-free facility were negative for viral sequences. Methodology: We examined xenograft tumor cell lines from seven independent laboratories and 128 non-xenografted tumor cell lines. Cell line DNA was examined for mouse DNA contamination, and by 3 Taqman qPCR assays targeting the gag, env or pol regions of MLV. Sequencing was used for viral strain identification. Supernatant fluids were tested for reverse transcriptase (RT) activity. Conclusions: Human cultures derived after mouse xenografting frequently contain and release highly infectious xenotropic MLV viruses. Laboratories working with xenograft-derived human cultures should be aware of the risk of contamination with potentially biohazardous human-tropic mouse viruses and their horizontal spread to other cultures.

Original languageEnglish (US)
Pages (from-to)617-628
Number of pages12
JournalCancer Biology and Therapy
Volume12
Issue number7
DOIs
StatePublished - Oct 1 2011

Fingerprint

Murine Leukemia Viruses
Heterografts
Cell Line
RNA-Directed DNA Polymerase
Tumor Cell Line
Xenotropic murine leukemia virus-related virus
DNA Contamination
Viruses
Heterologous Transplantation
DNA
Virion
Cell Culture Techniques

Keywords

  • Cell cultures
  • Lung cancer
  • Prostate cell line
  • Retrovirus
  • Xenograft cultures
  • Xenotropic murine leukemia virus
  • XMRV virus

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Frequent detection of infectious xenotropic murine leukemia virus (XMLV) in human cultures established from mouse xenografts. / Zhang, Yu An; Maitra, Anirban; Hsieh, Jer Tsong; Rudin, Charles M.; Peacock, Craig D.; Karikari, Collins; Brekken, Rolf A.; Stastny, Victor; Gao, Boning; Girard, Luc; Wistuba, Ignacio; Frenkel, Eugene; Minna, John D.; Gazdar, Adi F.

In: Cancer Biology and Therapy, Vol. 12, No. 7, 01.10.2011, p. 617-628.

Research output: Contribution to journalArticle

Zhang, Yu An ; Maitra, Anirban ; Hsieh, Jer Tsong ; Rudin, Charles M. ; Peacock, Craig D. ; Karikari, Collins ; Brekken, Rolf A. ; Stastny, Victor ; Gao, Boning ; Girard, Luc ; Wistuba, Ignacio ; Frenkel, Eugene ; Minna, John D. ; Gazdar, Adi F. / Frequent detection of infectious xenotropic murine leukemia virus (XMLV) in human cultures established from mouse xenografts. In: Cancer Biology and Therapy. 2011 ; Vol. 12, No. 7. pp. 617-628.
@article{74cb455ab1214a7cbe1d863d3012dd30,
title = "Frequent detection of infectious xenotropic murine leukemia virus (XMLV) in human cultures established from mouse xenografts",
abstract = "Purpose: To investigate the frequency of xenotropic murine leukemia virus (MLV) presence in human cell lines established from mouse xenografts and to search for the evidence of horizontal viral spread to other cell lines. Results: Six of 23 (26{\%}) mouse DNA free xenograft cultures were strongly positive for MLV and their sequences had greater than 99{\%} homology to known MLV strains. Four of five available supernatant fluids from these viral positive cultures were strongly positive for RT activity. Three of these supernatant fluids were studied to confirm the infectivity of the released virions for other human culture cells. Of the 78 non-xenograft derived cell lines maintained in the xenograft culture-containing facilities, 13 (17{\%}) were positive for MLV, including XMRV, a virus strain first identified in human tissues. By contrast, all 50 cultures maintained in a xenograft culture-free facility were negative for viral sequences. Methodology: We examined xenograft tumor cell lines from seven independent laboratories and 128 non-xenografted tumor cell lines. Cell line DNA was examined for mouse DNA contamination, and by 3 Taqman qPCR assays targeting the gag, env or pol regions of MLV. Sequencing was used for viral strain identification. Supernatant fluids were tested for reverse transcriptase (RT) activity. Conclusions: Human cultures derived after mouse xenografting frequently contain and release highly infectious xenotropic MLV viruses. Laboratories working with xenograft-derived human cultures should be aware of the risk of contamination with potentially biohazardous human-tropic mouse viruses and their horizontal spread to other cultures.",
keywords = "Cell cultures, Lung cancer, Prostate cell line, Retrovirus, Xenograft cultures, Xenotropic murine leukemia virus, XMRV virus",
author = "Zhang, {Yu An} and Anirban Maitra and Hsieh, {Jer Tsong} and Rudin, {Charles M.} and Peacock, {Craig D.} and Collins Karikari and Brekken, {Rolf A.} and Victor Stastny and Boning Gao and Luc Girard and Ignacio Wistuba and Eugene Frenkel and Minna, {John D.} and Gazdar, {Adi F.}",
year = "2011",
month = "10",
day = "1",
doi = "10.4161/cbt.12.7.15955",
language = "English (US)",
volume = "12",
pages = "617--628",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "7",

}

TY - JOUR

T1 - Frequent detection of infectious xenotropic murine leukemia virus (XMLV) in human cultures established from mouse xenografts

AU - Zhang, Yu An

AU - Maitra, Anirban

AU - Hsieh, Jer Tsong

AU - Rudin, Charles M.

AU - Peacock, Craig D.

AU - Karikari, Collins

AU - Brekken, Rolf A.

AU - Stastny, Victor

AU - Gao, Boning

AU - Girard, Luc

AU - Wistuba, Ignacio

AU - Frenkel, Eugene

AU - Minna, John D.

AU - Gazdar, Adi F.

PY - 2011/10/1

Y1 - 2011/10/1

N2 - Purpose: To investigate the frequency of xenotropic murine leukemia virus (MLV) presence in human cell lines established from mouse xenografts and to search for the evidence of horizontal viral spread to other cell lines. Results: Six of 23 (26%) mouse DNA free xenograft cultures were strongly positive for MLV and their sequences had greater than 99% homology to known MLV strains. Four of five available supernatant fluids from these viral positive cultures were strongly positive for RT activity. Three of these supernatant fluids were studied to confirm the infectivity of the released virions for other human culture cells. Of the 78 non-xenograft derived cell lines maintained in the xenograft culture-containing facilities, 13 (17%) were positive for MLV, including XMRV, a virus strain first identified in human tissues. By contrast, all 50 cultures maintained in a xenograft culture-free facility were negative for viral sequences. Methodology: We examined xenograft tumor cell lines from seven independent laboratories and 128 non-xenografted tumor cell lines. Cell line DNA was examined for mouse DNA contamination, and by 3 Taqman qPCR assays targeting the gag, env or pol regions of MLV. Sequencing was used for viral strain identification. Supernatant fluids were tested for reverse transcriptase (RT) activity. Conclusions: Human cultures derived after mouse xenografting frequently contain and release highly infectious xenotropic MLV viruses. Laboratories working with xenograft-derived human cultures should be aware of the risk of contamination with potentially biohazardous human-tropic mouse viruses and their horizontal spread to other cultures.

AB - Purpose: To investigate the frequency of xenotropic murine leukemia virus (MLV) presence in human cell lines established from mouse xenografts and to search for the evidence of horizontal viral spread to other cell lines. Results: Six of 23 (26%) mouse DNA free xenograft cultures were strongly positive for MLV and their sequences had greater than 99% homology to known MLV strains. Four of five available supernatant fluids from these viral positive cultures were strongly positive for RT activity. Three of these supernatant fluids were studied to confirm the infectivity of the released virions for other human culture cells. Of the 78 non-xenograft derived cell lines maintained in the xenograft culture-containing facilities, 13 (17%) were positive for MLV, including XMRV, a virus strain first identified in human tissues. By contrast, all 50 cultures maintained in a xenograft culture-free facility were negative for viral sequences. Methodology: We examined xenograft tumor cell lines from seven independent laboratories and 128 non-xenografted tumor cell lines. Cell line DNA was examined for mouse DNA contamination, and by 3 Taqman qPCR assays targeting the gag, env or pol regions of MLV. Sequencing was used for viral strain identification. Supernatant fluids were tested for reverse transcriptase (RT) activity. Conclusions: Human cultures derived after mouse xenografting frequently contain and release highly infectious xenotropic MLV viruses. Laboratories working with xenograft-derived human cultures should be aware of the risk of contamination with potentially biohazardous human-tropic mouse viruses and their horizontal spread to other cultures.

KW - Cell cultures

KW - Lung cancer

KW - Prostate cell line

KW - Retrovirus

KW - Xenograft cultures

KW - Xenotropic murine leukemia virus

KW - XMRV virus

UR - http://www.scopus.com/inward/record.url?scp=80053405084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053405084&partnerID=8YFLogxK

U2 - 10.4161/cbt.12.7.15955

DO - 10.4161/cbt.12.7.15955

M3 - Article

C2 - 21750403

AN - SCOPUS:80053405084

VL - 12

SP - 617

EP - 628

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

SN - 1538-4047

IS - 7

ER -