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Identification of the envelope V3 loop as a determinant of a CD4-negative neuronal cell tropism for HIV-1
J R Trujillo1, W K Wang, T H Lee
1Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Insights
Human immunodeficiency virus type 1 (HIV-1) can infect CD4-negative cells. Changes in the V3 loop of HIV-1 gp120 significantly impact infectivity in these cells, suggesting V3 is a key determinant.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Some neuronal cells lacking CD4 receptors are susceptible to human immunodeficiency virus type 1 (HIV-1) infection.
- Galactosyl ceramide acts as an alternative HIV-1 receptor, binding to gp120 regions C2, V3, V4, and V5 in vitro.
- The impact of V3 loop amino acid variations on HIV-1 tropism in CD4-negative cells remains largely uncharacterized.
Purpose of the Study:
- To investigate the effect of amino acid variations within the V3 loop of gp120 on HIV-1 infectivity in CD4-negative neuronal cells.
- To determine if the V3 loop is a primary determinant of HIV-1 infection in CD4-negative neuronal cells.
Main Methods:
- Analysis of HIV-1 V3 loop sequences and their correlation with infectivity.
- Infection assays using the CD4-negative neuronal cell line SK-N-MC.
- Assessment of a V3 loop-neutralizing monoclonal antibody's efficacy in blocking HIV-1 infection.
Main Results:
- Significant alterations in HIV-1 infectivity were observed based on V3 domain sequence variations.
- A monoclonal antibody targeting the gp120 V3 loop effectively inhibited HIV-1 infection of SK-N-MC cells.
- These findings indicate a crucial role for the V3 loop in mediating HIV-1 entry into CD4-negative neuronal cells.
Conclusions:
- The V3 loop of HIV-1 gp120 plays a critical role in determining viral infectivity in CD4-negative neuronal cells.
- Targeting the V3 loop presents a potential strategy for inhibiting HIV-1 infection in these cell types.
Abstract:
Some neuronal-derived CD4-negative cells are susceptible to infection with human immunodeficiency virus type 1 (HIV-1). Galactosyl ceramide is an alternate receptor for HIV-1 that appears to bind in vitro to the C2, V3, V4, and V5 regions of gp120. Amino acid variation in the V3 loop of HIV-1 affects cellular tropism in CD4-positive cells, but its effect on CD4-negative cells has not been fully analyzed. Here, we describe the effect of amino acid changes in V3 on the HIV-1 infection of a CD4-negative neuronal cell line, SK-N-MC. The sequence of the V3 domain was found to dramatically alter virus infectivity. Furthermore, a gp120 V3 loop neutralizing monoclonal antibody blocked HIV-1 infection of SK-N-MC cells. This data suggests that V3 may also serve as a primary viral determinant for infectivity of CD4-negative cells.