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Pathogenesis and Immunity

Astrocytes Survive Chronic Infection and Cytopathic Effects of the ts1 Mutant of the Retrovirus Moloney Murine Leukemia Virus by Upregulation of Antioxidant Defenses

Wenan Qiang, Xianghong Kuang, Jinrong Liu, Na Liu, Virginia L. Scofield, Amy J. Reid, Yuhong Jiang, Gheorghe Stoica, William S. Lynn, Paul K. Y. Wong
Wenan Qiang
Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957
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  • For correspondence: pkwong@mdanderson.org w-qiang@northwestern.edu
Xianghong Kuang
Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957
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Jinrong Liu
Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957
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Na Liu
Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957
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Virginia L. Scofield
Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957
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Amy J. Reid
Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957
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Yuhong Jiang
Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957
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Gheorghe Stoica
Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957
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William S. Lynn
Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957
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Paul K. Y. Wong
Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957
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  • For correspondence: pkwong@mdanderson.org w-qiang@northwestern.edu
DOI: 10.1128/JVI.80.7.3273-3284.2006
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ABSTRACT

The ts1 mutant of Moloney murine leukemia virus (MoMuLV) induces a neurodegenerative disease in mice, in which glial cells are infected by the retrovirus but neurons are not. ts1 infection of primary astrocytes, or of the immortalized astrocytic cell line C1, results in accumulation of the ts1 gPr80env envelope protein in the endoplasmic reticulum (ER), with ER and oxidative stress. Notably, only about half of the infected astrocytes die in these cultures, while the other half survive, continue to proliferate, and continue to produce virus. To determine how these astrocytes survive ts1 infection in culture, we established a chronically infected subline of the living cells remaining after the death of all acutely infected cells in an infected C1 cell culture (C1-ts1-S). We report here that C1-ts1-S cells proliferate more slowly, produce less virus, show reduced H2O2 levels, increase their uptake of cystine, and maintain higher levels of intracellular GSH and cysteine compared to acutely infected or uninfected C1 cells. C1-ts1-S cells also upregulate their thiol antioxidant defenses by activation of the transcription factor NF-E2-related factor 2 (Nrf2) and its target genes. Interestingly, despite maintenance of higher levels of intracellular reduced thiols, C1-ts1-S cells are more sensitive to cystine deprivation than uninfected C1 cells. We conclude that some ts1-infected astrocytes survive and adapt to virus-induced oxidative stress by successfully mobilizing their thiol redox defenses.

  • Copyright © 2006 American Society for Microbiology
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Astrocytes Survive Chronic Infection and Cytopathic Effects of the ts1 Mutant of the Retrovirus Moloney Murine Leukemia Virus by Upregulation of Antioxidant Defenses
Wenan Qiang, Xianghong Kuang, Jinrong Liu, Na Liu, Virginia L. Scofield, Amy J. Reid, Yuhong Jiang, Gheorghe Stoica, William S. Lynn, Paul K. Y. Wong
Journal of Virology Mar 2006, 80 (7) 3273-3284; DOI: 10.1128/JVI.80.7.3273-3284.2006

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Astrocytes Survive Chronic Infection and Cytopathic Effects of the ts1 Mutant of the Retrovirus Moloney Murine Leukemia Virus by Upregulation of Antioxidant Defenses
Wenan Qiang, Xianghong Kuang, Jinrong Liu, Na Liu, Virginia L. Scofield, Amy J. Reid, Yuhong Jiang, Gheorghe Stoica, William S. Lynn, Paul K. Y. Wong
Journal of Virology Mar 2006, 80 (7) 3273-3284; DOI: 10.1128/JVI.80.7.3273-3284.2006
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KEYWORDS

Antioxidants
astrocytes
Leukemia, Experimental
Moloney murine leukemia virus
Retroviridae Infections
Tumor Virus Infections
Up-Regulation

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