Kaposi's sarcoma associated herpesvirus or human herpesvirus 8 (KSHV/HHV8) is a gamma herpesvirus that is the cause of Kaposi's sarcoma and body cavity lymphomas. During lytic reactivation, KSHV produces a highly abundant nuclear localized transcript, polyadenylated nuclear RNA, PAN RNA. PAN RNA was shown to regulate viral and cellular gene expression. One mechanism used by PAN RNA involves the mediation of changes in epigenetic modifications. A recombinant BACmid defective for PAN RNA expression fails to reactivate and produce supernatant virus. This established PAN RNA as an essential long non-coding RNA (lncRNA) for virus replication and growth. lncRNAs are defined as non protein coding transcripts longer than 200 bases. In mammalian cells lncRNAs are very abundant with numbers estimated in the tens of thousands and many are associated with disease. Many lncRNAs have now been characterized and have a broad range of functions. Many act to regulate transcription through a variety of mechanisms. lncRNAs can act as regulators of transcription by directly interacting with transcription factors as well as recruiting transcription complexes to specific promoters. For herpesviruses, several lncRNAs have now been identified including KSHV PAN RNA, human cytomegalovirus (HCMV) lncRNA4.9 and herpes simplex virus (HSV-1) LATs. However the full understanding of the role of herpesvirus encoded lncRNAs in infection is in its infancy. There is a critical need to define the function of herpesvirus lncRNAs and their contribution to virus replication and affects on cell gene expression.

Public Health Relevance

Kaposi's sarcoma associated herpesvirus or human herpesvirus 8 (KSHV/HHV8) is a gamma herpesvirus that is the cause of Kaposi's sarcoma and body cavity lymphomas. During lytic reactivation, KSHV produces a highly abundant nuclear localized transcript, polyadenylated nuclear RNA, PAN RNA. This study will focus on defining the functional role of PAN RNA for gene expression and viral immune evasion.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI123011-01A1
Application #
9203912
Study Section
AIDS-associated Opportunistic Infections and Cancer Study Section (AOIC)
Program Officer
Beisel, Christopher E
Project Start
2016-05-06
Project End
2021-04-30
Budget Start
2016-05-06
Budget End
2017-04-30
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Nevada Reno
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
146515460
City
Reno
State
NV
Country
United States
Zip Code
89557