Journal
FRONTIERS IN MICROBIOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2020.575255
Keywords
EBV; pre-latent phase; abortive lytic infection; fate mapping; neo virology
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) KAKENHI [JP16H06231, JP18H02662, JP19H04829, JP20H03493, JP19H04826, JP19H04839, JP17H04081]
- JST PRESTO [JPMJPR19H5]
- JST MIRAI [18077147]
- Japan Agency for Medical Research and Development (AMED) [JP19fm0208016, JP20wm0325012, JP19ck0106517, JP19jk0210023]
- Takeda Science Foundation
- Japanese Association of Medical Sciences
- Hori Sciences and Arts Foundation
- MSD Life Science Foundation
- Takeda Science Foundation scholarship
- JSPS Research fellowship [19J01713]
- Grants-in-Aid for Scientific Research [19J01713] Funding Source: KAKEN
Ask authors/readers for more resources
The study reveals that during Epstein-Barr virus infection, cell growth is reprogrammed and a burst of viral lytic gene expression occurs in the early stage of infection. Infectious virions are not produced in the pre-latent phase, indicating an abortive lytic infection, which ultimately converges to latent infection. The BZLF1 protein, a key regulator of reactivation, is found to be dispensable for abortive lytic infection in the pre-latent phase, suggesting divergent regulation of viral gene expressions from productive lytic infection.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available