Author:
Inagaki Tomoki,Sato Yoshitaka,Ito Jumpei,Takaki Mitsuaki,Okuno Yusuke,Yaguchi Masahiro,Masud H. M. Abdullah Al,Watanabe Takahiro,Sato Kei,Iwami Shingo,Murata Takayuki,Kimura Hiroshi
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.
Funder
Japan Society for the Promotion of Science
Japan Science and Technology Agency
Japan Agency for Medical Research and Development
Hori Sciences and Arts Foundation
MSD Life Science Foundation, Public Interest Incorporated Foundation
Subject
Microbiology (medical),Microbiology
Cited by
29 articles.
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