A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) In Vivo To Promote Latent Infection of Germinal Center B Cells

MBio
Yiping WangScott A Tibbetts

Abstract

Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), directly contribute to the genesis of multiple types of malignancies, including B cell lymphomas. In vivo, these viruses infect B cells and manipulate B cell biology to establish lifelong latent infection. To accomplish this, gammaherpesviruses employ an array of gene products, including microRNAs (miRNAs). Although numerous host mRNA targets of gammaherpesvirus miRNAs have been identified, the in vivo relevance of repression of these targets remains elusive due to species restriction. Murine gammaherpesvirus 68 (MHV68) provides a robust virus-host system to dissect the in vivo function of conserved gammaherpesvirus genetic elements. We identified here MHV68 mghv-miR-M1-7-5p as critical for in vivo infection and then validated host EWSR1 (Ewing sarcoma breakpoint region 1) as the predominant target for this miRNA. Using novel, target-specific shRNA-expressing viruses, we determined that EWSR1 repression in vivo was essential for germinal center B cell infection. These findings provide the first in vivo demonstration of the biological significance of repression of a specific host mRNA by a gammaherpesvir...Continue Reading

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Citations

Nov 20, 2020·Journal of Virology·Enrico R BarrozoDavid C Bloom
Sep 30, 2021·Annual Review of Virology·Yiping WangLaurie T Krug

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Methods Mentioned

BETA
cross-linking immunoprecipitation
PCR
nucleotide exchange
reverse transcription-PCR
transfection
PCRs
transfections
protein assay

Software Mentioned

FlowJo
ImageJ
Invitrogen Block - iT
Bio
qCLASH
Mfold
GraphPad Prism
Rad CFX Manager

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