Herpesviruses are endemic within the human population, and cause a wide range of life-threatening diseases. Members of the betaherpesvirus and gammaherpesvirus subfamilies are extremely problematic in immunocompromised individuals, leading to severe congenital disorders and a variety of cancers. This proposal will define how a critical class of herpesviral genes are expressed late in the lifecycle of Kaposi's sarcoma-associated herpesvirus (KSHV) through a mechanism that involves a novel transcription complex, which combines both viral mimicry and co-option of select host machinery. The set of viral proteins required for late gene activation are broadly conserved among the beta- and gammaherpesviruses, indicating that information gained herein for KSHV will likely be applicable for Epstein-Barr virus and human cytomegalovirus as well. The focus of this grant is to define the composition and regulation of this novel gene expression complex, and reveal how its function is linked to viral genome replication. Given that even subtle mutations in this late gene transcription complex effectively `kill' the virus, an understanding of its composition and regulation is anticipated to reveal new targets for antiviral strategies.

Public Health Relevance

Kaposi's sarcoma-associated herpesvirus (KSHV) is an emerging Group 1 pathogen and the major cause of cancers in untreated AIDS patients. KSHV, like other DNA viruses, expresses a class of genes late during infection that are essential for viral assembly and escape from their host cell, but how the expression of these genes is regulated has long remained unknown. This grant is focused on revealing how a group of KSHV proteins orchestrates this process though a combination of molecular mimicry and co-option of host gene expression machinery.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI122528-06A1
Application #
10223851
Study Section
Virology - B Study Section (VIRB)
Program Officer
Gautam, Rajeev
Project Start
2015-11-13
Project End
2026-02-28
Budget Start
2021-03-10
Budget End
2022-02-28
Support Year
6
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Other Basic Sciences
Type
Earth Sciences/Resources
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94710