Histidine-Rich Glycoprotein Inhibits HIV-1 Infection in a pH-Dependent Manner

Area of Science:

• Virology
• Immunology
• Biochemistry

Background:

• Histidine-rich glycoprotein (HRG) is a plasma protein that interacts with various ligands and regulates biological responses.
• Mucosal surfaces, particularly the female genital tract, are key sites for viral transmission, yet protective host factors are not fully understood.

Purpose of the Study:

• To investigate the antiviral activity of HRG against HIV-1 infection.
• To determine the role of pH in HRG-mediated antiviral effects.
• To explore the potential of HRG as a natural defense mechanism against mucosal viral transmission.

Main Methods:

• Infection assays using various cell types (Ghost, Jurkat, CD4+ T cells, macrophages, HEp-2, Vero) with HIV-1, RSV, and HSV-2.
• pH manipulation of cell culture conditions (low pH 5.5-6.5 vs. neutral pH).
• Assessment of HRG's interaction with target cell heparan sulfate and its effect on viral particles.

Main Results:

• HRG significantly inhibited HIV-1 infection of multiple cell types at low pH but not at neutral pH.
• HRG's antiviral mechanism involves interaction with heparan sulfate on target cells and direct deleterious effects on the HIV-1 virion.
• HRG also demonstrated broad antiviral activity against RSV and HSV-2 at acidic pH.

Conclusions:

• Low pH enables histidine-rich glycoprotein (HRG) to potently inhibit HIV-1 infection by affecting both viral particles and host cell interactions.
• HRG's pH-dependent antiviral activity suggests it functions as a constitutive defense mechanism within the acidic environment of the vaginal mucosa.
• HRG exhibits broad-spectrum antiviral potential against various viruses under acidic conditions, highlighting its significance in mucosal immunity.