Following human immunodeficiency virus (HIV) membrane fusion with the target cell membrane, a series of events occur to establish an infection. Specifically, early in the life cycle, the virus must reverse transcribe its RNA genome and induce the transport of this genome to the nuclear envelope for subsequent nuclear import and integration. At some point prior to the nuclear import of the viral genome, the virus undergoes the poorly understood process of uncoating, defined as the disassembly of the assembled capsid structure from the viral ribonucleoprotein complex. However, the precise mechanism of uncoating remains elusive. The foundation of this application is the hypothesis that uncoating is influenced by the interaction between the mature, assembled viral capsid lattice and microtubule motor proteins and/or microtubule- associated proteins (MAPs). We provide evidence that MT disruption inhibits HIV-1 uncoating and propose to utilize assays to measure uncoating, live cell imaging assays and capsid binding assays to identify the MAPs which are involved in facilitating HIV-1 uncoating.

Public Health Relevance

During Human Immunodeficiency Virus Type-1 (HIV-1) infection, the virus sheds protein from its capsid core containing the viral genome. Although the process of uncoating is poorly understood, many recent studies suggest that this replicative step may be targeted in therapeutic intervention strategies. Here, we will explore the role that microtubule transport and microtubule associated proteins have on HIV-1 uncoating.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI106547-02
Application #
8707967
Study Section
AIDS Molecular and Cellular Biology Study Section (AMCB)
Program Officer
Sharma, Opendra K
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Loyola University Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Maywood
State
IL
Country
United States
Zip Code
60153