Abstract
Viral infection induces dynamic changes in transcriptional profiles. Virus-induced and antiviral responses are intertwined during the infection. Epstein-Barr virus (EBV) is a human gammaherpesvirus that provides a model of herpesvirus latency. To measure the transcriptome changes during the establishment of EBV latency, we infected EBV-negative Akata cells with EBV-EGFP and performed transcriptome sequencing (RNA-seq) at 0, 2, 4, 7, 10, and 14 days after infection. We found transient downregulation of mitotic division-related genes, reflecting reprogramming of cell growth by EBV, and a burst of viral lytic gene expression in the early phase of infection. Experimental and mathematical investigations demonstrate that infectious virions were not produced in the pre-latent phase, suggesting the presence of an abortive lytic infection. Fate mapping using recombinant EBV provided direct evidence that the abortive lytic infection in the pre-latent phase converges to latent infection during EBV infection of B-cells, shedding light on novel roles of viral lytic gene(s) in establishing latency. Furthermore, we find that the BZLF1 protein, which is a key regulator of reactivation, was dispensable for abortive lytic infection in the pre-latent phase, suggesting the divergent regulation of viral gene expressions from a productive lytic infection.
Highlights
Numerous signaling events are triggered during the first few days of viral infection
We address the fate of infected cells, which exhibit an abortive lytic infection, during Epstein-Barr virus (EBV) infection and record lytic gene expression by fate mapping with recombinant EBV
We used Akata cells, the Burkitt lymphoma cell line, instead of primary B-cells, because we focus on the infection-mediated transcriptional changes during EBV infection without EBVdriven transformation and further subsequent analysis using genetics
Summary
Numerous signaling events are triggered during the first few days of viral infection. Virus entry into the target cells results in the activation of cellular signaling pathways (Hiscott et al, 2001). BZLF1-Independent Abortive Lytic EBV Infection this interspecies interaction to meet their own needs and, establish latency in their host cells. Epstein-Barr virus (EBV), a gammaherpesvirus, is a widely dispersed enveloped virus that infects > 90% of adults worldwide. It is associated with several types of human malignancies with an incidence of 200,000 EBVrelated cancers estimated annually (Cohen et al, 2011). EBV provides a model system for studying how viruses, and herpesviruses, establish latency in the cells
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