Mechanisms of Viral Persistence

Information

  • Research Project
  • 10221520
  • ApplicationId
    10221520
  • Core Project Number
    R01AI085043
  • Full Project Number
    5R01AI085043-13
  • Serial Number
    085043
  • FOA Number
    PA-19-056
  • Sub Project Id
  • Project Start Date
    12/1/2009 - 14 years ago
  • Project End Date
    6/30/2024 - 11 days from now
  • Program Officer Name
    JIANG, CHAO
  • Budget Start Date
    7/1/2021 - 2 years ago
  • Budget End Date
    6/30/2022 - a year ago
  • Fiscal Year
    2021
  • Support Year
    13
  • Suffix
  • Award Notice Date
    7/7/2021 - 2 years ago

Mechanisms of Viral Persistence

PROJECT SUMMARY/ABSTRACT Chronic viral infections and the co-infections they foster are among the greatest health concerns worldwide. Although their linkage is clear, it is much less clear how one pathogen alters the immune environment to foster another. T cells are critical both to control chronic virus infections and to correctly orchestrate de novo immune responses against co-infecting pathogens. Thus, we surmised that if the immune environment during chronic virus infection altered the ability to appropriately mount T cell responses, that it would jointly and simultaneously affect the chronic infection and susceptibility / severity of secondary infections. The goal of this proposal is to investigate how chronic inflammation and the evolving host:pathogen interactions as viral persistence progresses alters immunity to co-infecting pathogens. To achieve this goal, we have developed a novel mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection and Mycobacterium tuberculosis (Mtb) co-infection. Our preliminary data demonstrate that in the presence of established chronic viral infection, Mtb specific immune responses are delayed, redirected and Mtb replication increased. In the current proposal, we will mechanistically investigate how the modulation of the immune response by the chronic virus spreads to delay acquired Mtb-specific immunity and determine the mechanistic basis through which the altered T cell immunity enhances Mtb disease progression. We will then examine the reciprocal relationship between established Mtb infection and chronic viral co-infection to understand how they comparatively impact the ability to generate and sustain simultaneous immune responses and modulate disease course. The experiments outlined in this proposal will establish important biologic principles and provide a new mechanistic link between the host:pathogen interactions that foster viral persistence with those that enhance susceptibility to and severity of secondary infections. Ultimately, the mechanisms and paradigms we reveal have the potential to lead to new strategies to treat chronic viral infections and the co-infections that plague them.

IC Name
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
  • Activity
    R01
  • Administering IC
    AI
  • Application Type
    5
  • Direct Cost Amount
    300000
  • Indirect Cost Amount
    24000
  • Total Cost
    324000
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    855
  • Ed Inst. Type
  • Funding ICs
    NIAID:324000\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    IHD
  • Study Section Name
    Immunity and Host Defense
  • Organization Name
    UNIVERSITY HEALTH NETWORK
  • Organization Department
  • Organization DUNS
    208469486
  • Organization City
    TORONTO
  • Organization State
    ON
  • Organization Country
    CANADA
  • Organization Zip Code
    M5G 2C4
  • Organization District
    CANADA