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Journal of Virology, August 2010, p. 7448-7458, Vol. 84, No. 15
0022-538X/10/$012.00+0     doi:10.1128/JVI.00024-10
Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Enhancement of Autophagy during Lytic Replication by the Kaposi's Sarcoma-Associated Herpesvirus Replication and Transcription Activator {triangledown}

Hui-Ju Wen, Zhilong Yang, You Zhou, and Charles Wood*

Nebraska Center for Virology and the School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68583

Received 6 January 2010/ Accepted 10 May 2010

Autophagy is one of two major degradation systems in eukaryotic cells. The degradation mechanism of autophagy is required to maintain the balance between the biosynthetic and catabolic processes and also contributes to defense against invading pathogens. Recent studies suggest that a number of viruses can evade or subvert the host cell autophagic pathway to enhance their own replication. Here, we investigated the effect of autophagy on the KSHV (Kaposi's sarcoma-associated herpesvirus) life cycle. We found that the inhibition of autophagy reduces KSHV lytic reactivation from latency, and an enhancement of autophagy can be detected during KSHV lytic replication. In addition, RTA (replication and transcription activator), an essential viral protein for KSHV lytic reactivation, is able to enhance the autophagic process, leading to an increase in the number of autophagic vacuoles, an increase in the level of the lipidated LC3 protein, and the formation of autolysosomes. Moreover, the inhibition of autophagy affects RTA-mediated lytic gene expression and viral DNA replication. These results suggest that RTA increases autophagy activation to facilitate KSHV lytic replication. This is the first report demonstrating that autophagy is involved in the lytic reactivation of KSHV.


* Corresponding author. Mailing address: 102C Morrison Life Sciences Research Center, 4240 Fair St., East Campus, University of Nebraska-Lincoln, Lincoln, NE 68583-0900. Phone: (402) 472-4550. Fax: (402) 472-3323. E-mail: cwood{at}unlnotes.unl.edu

{triangledown} Published ahead of print on 19 May 2010.


Journal of Virology, August 2010, p. 7448-7458, Vol. 84, No. 15
0022-538X/10/$012.00+0     doi:10.1128/JVI.00024-10
Copyright © 2010, American Society for Microbiology. All Rights Reserved.