The first step of viral infection is binding of virus to its target cells. Binding of HIV is usually mediated by viral envelope proteins, gp120, and its receptors, including CD4 and DC-SIGN. Therefore, previous studies of HIV binding have mainly focused on the interaction between gp120 and their receptors. We have recently found an envelope- protein independent manner of virus binding. One type of viral envelope lipid called phosphatidylserine binds to its receptors on target cells and mediates virus attachment. Since phosphatidylserine is specifically exposed on apoptotic cells, phosphatidylserine receptors are typically used for removal of apoptotic cells by phagocytes. We found that HIV replication is also drastically enhanced by one specific type of phosphatidylserine receptor, TIM-1, which is expressed on CD4-positive cells. In the proposed studies, we will investigate the molecular mechanism by which envelope phosphatidylserine and TIM-1 facilitates viral replication and whether CD300a, which is a newly identified phosphatidylserine receptor expressed on macrophages, can also support HIV replication. We will also investigate how HIV exposes phosphatidylserine on viral envelope. These studies will open a new avenue in HIV replication mechanism and help develop novel antiviral strategies that target phosphatidylserine-mediated viral replication.

Public Health Relevance

Binding of HIV is usually mediated by an envelope protein (gp120);thus, current antiviral strategies to block virus binding are mainly directed at gp120. We recently found that envelope viruses can use a certain type of envelope lipid called phosphatidylserine to bind to their target cells. Elucidation of this novel entry mechanism in HIV infection will lead to novel approaches for the prevention and therapy of HIV infection, and will be applicable to other types of viral infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI108400-01
Application #
8602737
Study Section
AIDS Molecular and Cellular Biology Study Section (AMCB)
Program Officer
Sanders, Brigitte E
Project Start
2013-06-19
Project End
2017-05-31
Budget Start
2013-06-19
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$325,710
Indirect Cost
$114,210
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095