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Journal of Virology, October 2001, p. 9165-9176, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9165-9176.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

High Resistance of Human Parainfluenza Type 2 Virus Protein-Expressing Cells to the Antiviral and Anti-Cell Proliferative Activities of Alpha/Beta Interferons: Cysteine-Rich V-Specific Domain Is Required for High Resistance to the Interferons

Machiko Nishio, Masato Tsurudome, Morihiro Ito, Mitsuo Kawano, Hiroshi Komada, and Yasuhiko Ito*

Department of Microbiology, Mie University School of Medicine, Tsu-Shi, Mie-Ken 514-8507, Japan

Received 23 April 2001/Accepted 6 July 2001

Human parainfluenza type 2 virus (hPIV-2)-infected HeLa (HeLa-CA) cells and hPIV-2 V-expressing HeLa (HeLa-V) cells show high resistance to alpha/beta interferons (IFN-alpha /beta ) irrespective of whether vesicular stomatitis virus or Sindbis virus is used as a challenge virus. When Sindbis virus is used, these cells show high susceptibility to human IFN-gamma . Furthermore, the multiplication of HeLa-V cells is not inhibited by IFN-alpha /beta . HeLa cells expressing the N-terminally truncated V protein show resistance to IFN-alpha /beta , showing that the IFN resistance determinant maps to the cysteine-rich V-specific domain. A complete defect of Stat2 is found in HeLa-CA and HeLa-V cells, whereas the levels of Stat1 expression are not significantly different among HeLa, HeLa-CA, HeLa-P, and HeLa-V cells, indicating that IFN-alpha /beta resistance of HeLa-CA and HeLa-V cells is due to a defect of Stat2. HeLa-SV41V cells show high resistance to all IFNs, and no expression of Stat1 can be detected. Stat2 mRNA is fully detected in HeLa-V cells. Stat2 was scarcely pulse-labeled in the HeLa-V cells, indicating that synthesis of Stat2 is suppressed or Stat2 is very rapidly degraded in HeLa-V cells. The V protein suppresses the in vitro translation of Stat2 mRNA more extensively than that of Stat1 mRNA. An extremely small amount of Stat2 can be detected in HeLa-V cells treated with proteasome inhibitors. The half-life of Stat2 is approximately 3.5 and 2 h in uninfected and hPIV-2-infected HeLa cells, respectively. This study shows that synthesis of Stat2 may be suppressed and Stat2 degradation is also enhanced in hPIV-2-infected HeLa and HeLa-V cells.

* Corresponding author. Mailing address: Department of Microbiology, Mie University School of Medicine, 2-174, Edobashi, Tsu-Shi, Mie-Ken, 514-8507, Japan. Phone and fax: 81-59-231-5008. E-mail: ito{at}doc.medic.mie-u.ac.jp.

Journal of Virology, October 2001, p. 9165-9176, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9165-9176.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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