P-D4 Tyrosine-sulfated peptides from the gp120 V2 domain block HIV-1 entry through CCR5 Mimicry. (January 2016)

• Record Type: Journal Article
• Authors: Liu, Qingbo; Cimbro, Raffaello; Guzzo, Christina; Zhang, Peng; Miao, Huiyi; Ryk, Donald; Dolan, Michael; Lusso, Paolo
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 71(2016)Supplement 1
• Publication Date: 2016-01
• Subjects: AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/01.qai.0000479629.55268.bb
• Languages: English
• ISSNs: 1525-4135

Abstract

Abstract : We recently identified 2 sulfated tyrosines, Tys173 and Tys177, in the second variable (V2) region of HIV-1 gp120 and shown that they play a role in stabilizing the pre-fusion conformation of the envelope trimer. The sulfated region of V2 has a high similarity with the N-terminal domain of CCR5, which also contains sulfated tyrosines and interacts with V3-loop base of gp120, suggesting a potential intramolecular interaction mode between V2 and V3. Here, we employed a tyrosine- sulfated V2-derived peptide, pV2alpha-Tys, to investigate binding to gp120 and its functional consequences. A direct interaction was observed between peptide pV2alpha-Tys and the base of V3, with Tys177 playing a dominant role. Surface plasmon resonance showed that binding of the pV2alpha-Tys is enhanced by CD4-induced conformational changes in gp120, and the effect is even more significant with a soluble trimer. Functionally, pV2alpha-Tys inhibits HIV-1 entry and fusion by preventing CCR5 utilization, with a potency comparable to that of a sulfated CCR5 N-terminal peptide, pCCR5-Tys. These studies characterize the structural and functional features of the V2–V3 intramolecular interaction, providing new leads for the design of therapeutic and vaccine strategies for the control of HIV/AIDS.