Suppression of lytic replication of Kaposi's sarcoma-associated herpesvirus by autophagy during initial infection in NIH 3T3 fibroblasts
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  • 作者:Gun-Hee Jang ; Jihui Lee ; Na-Yeon Kim ; Jae-Hyeon Kim ; Jung-Yong Yeh…
  • 刊名:Archives of Virology
  • 出版年:2016
  • 出版时间:March 2016
  • 年:2016
  • 卷:161
  • 期:3
  • 页码:595-604
  • 全文大小:664 KB
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  • 作者单位:Gun-Hee Jang (1)
    Jihui Lee (1)
    Na-Yeon Kim (1)
    Jae-Hyeon Kim (1)
    Jung-Yong Yeh (1) (2)
    Minsub Han (3)
    Soon Kil Ahn (1) (2)
    Hara Kang (1) (2)
    Michael Lee (1) (2)

    1. Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 406-772, Korea
    2. Institute for New Drug Development, Incheon National University, Incheon, 406-772, Korea
    3. Division of Mechanical Engineering, College of Engineering, Incheon National University, Incheon, 406-772, Korea
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Biomedicine
    Virology
    Medical Microbiology
    Infectious Diseases
  • 出版者:Springer Wien
  • ISSN:1432-8798
文摘
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the infectious cause of the angioproliferative neoplasm Kaposi’s sarcoma (KS). We first confirmed the susceptibility of NIH 3T3 fibroblasts to KSHV by infecting them with BCP-1-derived KSHV. Lytic replication of KSHV was confirmed by PCR amplification of viral DNA isolated from culture supernatants of KSHV-infected cells. The template from KSHV-infected NIH 3T3 cells resulted in an intense viral DNA PCR product. A time course experiment revealed the disappearance of KSHV-specific DNA in culture supernatant of NIH 3T3 cells during a period between 48 h and 72 h postinfection. Furthermore, 3 days postinfection, infected NIH 3T3 cells showed no evidence of latent or lytic transcripts, including LANA, vFLIP, vCyclin, and vIL-6. These results imply that KSHV infection in NIH 3T3 cells is unstable and is rapidly lost on subsequent culturing. Additionally, we detected an enhancement of autophagy early in infection with KSHV. More interestingly, inhibition of autophagy by Beclin 1 siRNA or 3-methyladenine significantly increased the amount of KSHV-specific DNA in the culture supernatant of NIH 3T3 cells when compared to the group treated with KSHV infection alone, implying that autophagy prevents lytic replication of KSHV. Taken together, our data suggest that autophagy could be one of the cellular mechanisms utilized by host cells to promote viral clearance.

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