Enhancement of autophagy during lytic replication by the Kaposi’s sarcoma-associated herpesvirus replication and transcription activator

Enhancement of autophagy during lytic replication by the Kaposi's sarcoma-associated herpesvirus replication and transcription activator

Human immunodeficiency virus type-1 (HIV-1) infection dramatically increases the risk of development of Kaposi’s sarcoma (KS) in individuals infected with Kaposi’s sarcoma-associated herpesvirus (KSHV). The balance between these two phases is critical for viral pathogenesis. Research has also focused on reactivating viral lytic replication in latently infected tumour cells (lytic induction therapy) to promote death of tumour cells. We showed that HIV-1 infection of primary effusion lymphoma cell lines triggered the reactivation of KSHV, as demonstrated by the expression of KSHV replication and transcription activator, the early viral lytic protein vIL-6 and ORF59 and the production of progeny virions. Furthermore, disruption of microtubules resulted in reduced levels of viral RNA while preservation of microtubule dynamics was most important during viral egress. An interdisciplinary approach, using rigorous biochemical and cell biological assays coupled with advanced microscopy strategies, will push to the next level our understanding of the virus-ER interaction during infection. Virol.

Enhancement of autophagy during lytic replication by the Kaposi's sarcoma-associated herpesvirus replication and transcription activator
In contrast to this hypothesis, recent studies have shown that replication of HSV and other large DNA viruses requires cellular proteins whose activities are normally regulated in a cell cycle dependent manner, such as the cyclin-dependent kinases (cdks). Dr. The stable 293T cells carrying the BAC36 and BACΔ6 genomes could be used as tools to investigate the detailed functions of ORF6 in the lytic replication of KSHV. 97 (2): 147–72. Conversely, ICP27 displayed an inhibitory effect. 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. Subsequent intracellular transport occurs either by the direct interaction of the virus with tubulins or via the endogenous endocytic pathway (Dohner and Sodeik, 2005 and Smith and Enquist, 2002). Additionally, because viral replication and assembly often occur in the context of virus-induced membranous structures derived from host membranes, the membranous network of choice should accommodate these remodeling reactions (Miller and Krijnse-Locker 2008). The role of LANA in the persistence of the KSHV genome was evaluated using the 33-kb left-end Z6 cosmid of KSHV in BJAB cells expressing LANA under G418 selection (4).

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