HIV-1 envelope glycoprotein gp120 third variable loop (gp120 V3 loop)

The HIV-1 envelope glycoprotein gp120 third variable (V3) loop is a critical 35-amino-acid region of the viral surface protein that facilitates entry into host cells [1]. It is primarily responsible for determining viral tropism, as it interacts directly with the host cell co-receptors CCR5 or CXCR4 after the initial binding of gp120 to the CD4 receptor [2]. This interaction triggers the necessary conformational changes in the gp41 subunit to initiate viral-cell membrane fusion [3]. Due to its high accessibility and functional importance, the V3 loop is a major target for neutralizing antibodies and is often referred to as the principal neutralizing determinant (PND) [4]. However, the loop is characterized by extreme sequence variability, which allows the virus to evade host immune responses and develop resistance to entry inhibitors [5]. Therapeutic strategies targeting this region include broadly neutralizing antibodies (bNAbs) like 10-1074 and small molecule inhibitors that interfere with the co-receptor binding interface [1][6]. [1] Huang, C. C., et al. (2005). "Structure of a V3-containing HIV-1 gp120 core." Science. [2] Wilen, C. B., et al. (2012). "HIV-1 Entry and Membrane Fusion." Cold Spring Harbor Perspectives in Medicine. [3] NIH/NIAID. (2023). "HIV Structure and Life Cycle." [4] Zolla-Pazner, S. (2004). "Focusing on the V3 loop for HIV vaccine design." Nature Reviews Immunology. [5] Fouchier, R. A., et al. (1992). "Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule." Journal of Virology. [6] Caskey, M., et al. (2017). "Antibody 10-1074 suppresses viremia in HIV-1-infected individuals." Nature Medicine.

Other names

V3 loopThird variable domain of gp120Principal neutralizing determinantPNDgp120 V3 domain

Entry inhibition by blocking the interaction between the V3 loop and host cell co-receptors (CCR5 or CXCR4) or neutralizing the virus by binding directly to the V3 loop glycans and peptide backbone.