The Role of Nucleopore Complex in the Nuclear Import of HIV-1

Samson Chow, University of California Los Angeles
Basic Biomedical Sciences
Innovative, Developmental, Exploratory Award (IDEA)

The ability to traverse an intact nuclear envelope and productively infect non-dividing cells is a salient feature of human immunodeficiency virus type 1 (HIV-1) and other lentiviruses, but the viral factors and mechanism of nuclear entry have not been defined. The overall goal of this application is to understand the nuclear import mechanism of HIV-1. For HIV-1 to productively infect a cell it must integrate its viral genome into the cell’s chromosomal DNA. However, before the essential step of integration can take place the virus must first negotiate an uncertain pathway through the cell’s cytoplasm to arrive at the nucleus. Once at the nucleus, the virus must then traverse the nuclear envelope, a selective and formidable barrier that regulates access to the cell’s chromosomal DNA. How the virus crosses the nuclear envelope is unknown, and represent a long standing question in HIV-1 biology. Our preliminary data suggest that the unique nuclear import property of the viral protein integrase may be important to the nuclear import of the virus. We have found that HIV-1 integrase interacts with NUP153, a nuclear envelope protein which functions as a nexus for transport between the cytoplasm and nucleus, to achieve nuclear import. We have also found that NUP153 can affect the ability of HIV-1 to infect cells. Based on our preliminary data, we have formulated a research plan that will focus on the following three specific aims: 1) to better understand the integrase-NUP153 interaction, and its significance in the nuclear import of HIV-1 integrase, 2) to determine the role of the integrase-NUP153 interaction in HIV-1 replication, and 3) to determine the role of the proteins associated with nuclear envelope in the lifecycle of the virus. The information gained from this application on the nuclear import of HIV-1 will have significant implications to the understanding of HIV-1 biology and cellular trafficking processes, devising alternative strategies in blocking HIV-1 infection, and developing improved gene delivery vectors.

Program Note: Project has been funded to characterize the interaction between IN and NUP153 and determine its role in the nuclear import of HIV-1.