Human immunodeficiency virus type 2 surface glycoprotein gp120 (gp120)

The Human immunodeficiency virus type 2 surface glycoprotein gp120 (also frequently referred to as gp125 or gp105) is the exterior subunit of the viral envelope (Env) spike and is fundamental for the initiation of the viral life cycle. It is generated through the proteolytic cleavage of the gp140 precursor protein and remains non-covalently associated with the transmembrane subunit gp36 to form a functional trimeric complex on the surface of the virion [2, 11, 14]. The primary biological function of gp120 is to mediate viral attachment and entry into host CD4+ T lymphocytes and macrophages. This process involves the high-affinity binding of gp120 to the host CD4 receptor, which triggers conformational changes that expose a binding site for a chemokine coreceptor, typically CCR5 or CXCR4 [2, 12, 15]. In the context of infection, gp120 is the primary determinant of viral tropism and a major driver of immune depletion and AIDS, although HIV-2 typically progresses more slowly than HIV-1 [11]. Therapeutic targeting of HIV-2 gp120 is particularly challenging due to its high sequence divergence from HIV-1 and its extensive glycosylation, which creates a 'glycan shield' that protects conserved epitopes from neutralizing antibodies [5, 16]. While entry inhibitors such as the CCR5 antagonist Maraviroc and the CD4-binding monoclonal antibody Ibalizumab are utilized to block the gp120-mediated entry pathway, direct attachment inhibitors like fostemsavir, which targets HIV-1 gp120, are naturally ineffective against HIV-2 due to critical structural differences [5]. Consequently, current clinical management of HIV-2 relies on combinations of other antiretroviral classes, and gp120 remains a focal point for the development of broadly neutralizing antibodies and novel entry inhibitors [9, 11, 14].

Other names

gp125gp105Surface proteinSUHIV-2 surface glycoproteinEnvelope glycoprotein gp120gp140 (precursor)

Entry inhibition achieved by blocking the sequential interaction of the viral gp120 protein with host cell primary receptors (CD4) or coreceptors (CCR5/CXCR4), thereby preventing membrane fusion.