HIV-1 gp41: Role in HIV entry and prevention

Interaction of the envelope glycoprotein gp120 of the human immunodeficiency virus type 1 (HIV-1) with CD4 molecules (HIV-1 receptor) and then with the chemokine receptors (a co-receptor for HIV-1) on the helper T lymphocytes and macrophages initiates viral entry into the target cells (1-4), and gp120 hence has priority over other virals proteins to be used for developing a subunit vaccine against HIV-1 in many laboratories. Nevertheless, over the last few years it has emerged that HIV-1 transmembrane glycoprotein gp14 plays a special role in HIV-1 entry into the target cells and in developing an effective HIV vaccine. A putative cellular receptor for HIV-1 gp41 has been characterised by three groups (5-8). Recent crystal structure analysis of gp41 indicates that two domains (N- and C-domain) on gp41 could play an important role in mediating membrane fusion and HIV-1 entry (9, 10). Moreover, several studies had provided experimental evidence that these two domains on gp41 could induce protective activity (11-15). Understanding the role of gp41 in HIV entry and prevention may promote developing effective HIV vaccine and anti-HIV drugs.