Enhancement of autophagy during lytic replication by the Kaposi's sarcoma-associated herpesvirus replication and transcription activator.
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.
Wen
Hui-Ju
HJ
Nebraska Center for Virology and the School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68583-0900, USA.
Yang
Zhilong
Z
Zhou
You
Y
Wood
Charles
C
D001343:Autophagy; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism; D014775:Virus Activation; D014779:Virus Replication
D004279:DNA, Viral; D017874:Immediate-Early Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D037521:Virulence Factors