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Published on: September 24, 2010
LFA-1 expression on target cells promotes human immunodeficiency virus type 1 infection and transmission
1New York University School of Medicine and Manhattan VA Medical Center, New York, New York 10010, USA. hioec01@med.nyu.edu
Insights
Leukocyte function-associated antigen-1 (LFA-1) enhances human immunodeficiency virus (HIV) infection processes, including initial entry, replication, and spread. Proper regulation of LFA-1 activity is crucial for controlling HIV infection stages.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human immunodeficiency virus (HIV) primarily uses CD4 and chemokine receptors for cell entry.
- Other cellular proteins, like LFA-1, and their ligands (ICAMs) are also implicated in HIV infection.
- LFA-1 and its ligands can be present on both infected cells and HIV virions.
Purpose of the Study:
- To investigate the role of LFA-1 expressed on target cells in various stages of HIV infection.
- To determine how different forms of LFA-1 (wild-type vs. constitutively active mutant) affect HIV replication and transmission.
Main Methods:
- Utilized Jurkat-derived Jbeta2.7 T-cell lines engineered to express wild-type LFA-1, a constitutively active LFA-1 mutant, or no LFA-1.
- Assessed the impact of these LFA-1 variants on initial HIV infection, viral replication, and cell-to-cell transmission.
Main Results:
- Wild-type LFA-1 expression significantly enhanced initial HIV infection processes, viral replication, and cell-to-cell transmission.
- A constitutively active LFA-1 mutant facilitated HIV entry and initial infection but failed to promote subsequent viral replication and spread.
- These findings highlight the differential roles of LFA-1 activity states in the HIV life cycle.
Conclusions:
- LFA-1 plays a significant role in multiple stages of HIV infection, from initial cell interaction to viral replication and transmission.
- The regulated activity of LFA-1, not just its expression, is critical for controlling HIV infection.
- Targeting LFA-1 interactions could offer new strategies for HIV intervention.
Abstract:
While CD4 and the chemokine receptors are the principal receptors for human immunodeficiency virus (HIV), other cellular proteins, such as LFA-1, are also involved in HIV infection. LFA-1 and its ligands, ICAM-1, ICAM-2, and ICAM-3, can be expressed on the cells infected by HIV, as well as on the HIV virions themselves. To examine the role of LFA-1 expressed on target cells in HIV infection, Jurkat-derived Jbeta2.7 T-cell lines that express either wild-type LFA-1, a constitutively active mutant LFA-1, or no LFA-1 were used. The presence of wild-type LFA-1 enhanced the initial processes of HIV infection, as well as the subsequent replication and transmission from cell to cell. In contrast, the constitutively active LFA-1 mutant failed to promote virus replication and spread, even though this mutant could help HIV enter cells and establish the initial infection. This study clearly demonstrates the contribution of LFA-1 in the different stages of HIV infection. Moreover, not only is LFA-1 expression important for initial HIV-cell interaction, subsequent replication, and transmission, but its activity must also be properly regulated.
