Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The human Integrator complex is required for Herpes Simplex Virus Type 1 infection

Award Number: F31AI202950
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/12/2027
PERIOD OF PERFORMANCE END DATE: 02/11/2028

Group Awards By:

View Award Description

The human Integrator complex is required for Herpes Simplex Virus Type 1 infection - Abstract Herpes Simplex Virus Type 1 (HSV-1) is a widespread, double-stranded DNA alpha herpesvirus best known for its capacity to establish lifelong latency within neurons. Although many infected individuals experience no symptoms or only recurrent oral lesions, HSV-1 remains the primary cause of fatal viral encephalitis and is a major contributor to infectious blindness. Despite its substantial global burden, no licensed vaccine against HSV- 1 exists and antiviral agents such as acyclovir provide only limited benefit unless administered early in the lytic phase. HSV-1 depends entirely on host RNA Polymerase II (RNAPII) to drive viral gene expression, yet the molecular mechanisms that coordinate interactions between viral factors and host transcriptional regulators remain poorly defined. This proposal seeks to close this critical gap by examining how the host RNAPII regulatory apparatus is modulated during HSV-1 infection. The Integrator Complex (INT) is a multi-subunit, modular assembly that engages paused RNAPII and facilitates promoter-proximal transcription termination. In doing so, INT suppresses expression of protein-coding genes and governs 3′-end processing of short noncoding transcripts, including enhancer RNAs (eRNAs). Work from the Wagner laboratory and others has demonstrated that INT carries out RNAPII termination via two separable enzymatic functions: an RNA endonuclease activity residing in Integrator subunit 11 (INTS11) and a phosphatase activity mediated by Protein Phosphatase 2A (PP2A), which directly associates with INTS8. Although INT is established as a central regulator of RNAPII dynamics, its contribution to HSV-1 infection remains largely unexplored. To probe this question, we generated an auxin-inducible degron (AID) system that enables rapid (<1 hr) depletion of Integrator components. Using this platform, we discovered that HSV-1 replication is severely impaired when Integrator is removed or when INTS11 endonuclease activity is lost. Further, applying a custom biochemical purification strategy that isolates Integrator-associated RNAPII complexes, we identified abundant and specific HSV-1 proteins that interact with Integrator during infection. Together, these findings support the hypothesis that Integrator activity is essential for efficient HSV-1 propagation and that HSV-1 proteins actively engage Integrator subunits during infection. To test this, I propose the following two Specific Aims: Aim 1: Delineate the Functional Role of INT in the HSV-1 Lifecycle. Aim2: Determine the interplay between HSV-1 proteins and INT subunits during HSV-1 infection.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $50,114 )
2026	2026	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Allergy and Infectious Diseases Research	000	1	8/12/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The human Integrator complex is required for Herpes Simplex Virus Type 1 infection

Award Number: F31AI202950

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/12/2027

PERIOD OF PERFORMANCE END DATE: 02/11/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer