Epstein–Barr virus EBER1 and murine gammaherpesvirus TMER4 share conserved in vivo function to promote B cell egress and dissemination

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 51; pp. 25392 - 25394
• Main Authors: Hoffman, Brett A., Wang, Yiping, Feldman, Emily R., Tibbetts, Scott A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.12.2019
• Series: Brief Report
• Subjects: Animals; Biological Sciences; BRIEF REPORTS; Cells, Cultured; Egress; Epstein-Barr virus; Gammaherpesvirinae - genetics; Herpesviridae Infections - virology; In vivo methods and tests; Kaposi's sarcoma; Latency; Lymph nodes; Lymphocytes B; Mice; Nucleic Acid Conformation; Peripheral circulation; Ribonucleic acid; RNA; RNA, Untranslated - chemistry; RNA, Untranslated - genetics; RNA, Untranslated - physiology; RNA, Viral - chemistry; RNA, Viral - genetics; RNA, Viral - physiology; Sarcoma; Spleen - cytology; Spleen - virology; Tumorigenesis; Virus Latency - genetics; Virus Release - genetics; Viruses; murine; EBV; EBER; noncoding RNA; herpesvirus
• DOI: 10.1073/pnas.1915752116
• ISSN: 0027-8424; 1091-6490

The oncogenic gammaherpesviruses, including human Epstein–Barr virus (EBV), human Kaposi’s sarcoma-associated herpesvirus (KSHV), and murine gammaherpesvirus 68 (MHV68, γHV68, MuHV-4) establish life-long latency in circulating B cells. The precise determinants that mediate in vivo gammaherpesvirus latency and tumorigenesis remain unclear. The EBV-encoded RNAs (EBERs) are among the first noncoding RNAs ever identified and have been the subject of decades of studies; however, their biological roles during in vivo infection remain unknown. Herein, we use a series of refined virus mutants to define the active isoform of MHV68 noncoding RNA TMER4 and demonstrate that EBV EBER1 functionally conserves this activity in vivo to promote egress of infected B cells from lymph nodes into peripheral circulation.