Select gp120 V2 domain specific antibodies derived from HIV and SIV infection and vaccination inhibit gp120 binding to α4β7

Sakaorat Lertjuthaporn*, Claudia Cicala, Donald Van Ryk, Matthew Liu, Jason Yolitz, Danlan Wei, Fatima Nawaz, Allison Doyle, Brooke Horowitch, Chung Park, Shan Lu, Yang Lou, Shixia Wang, Ruimin Pan, Xunqing Jiang, Francois Villinger, Siddappa N. Byrareddy, Philip J. Santangelo, Lynn Morris, Constantinos Kurt WibmerKristin Biris, Rosemarie D. Mason, Jason Gorman, Joseph Hiatt, Elena Martinelli, Mario Roederer, Dai Fujikawa, Giacomo Gorini, Genoveffa Franchini, Anush Arakelyan, Aftab A. Ansari, Kovit Pattanapanyasat, Xiang Peng Kong, Anthony S. Fauci, James Arthos

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The GI tract is preferentially targeted during acute/early HIV-1 infection. Consequent damage to the gut plays a central role in HIV pathogenesis. The basis for preferential targeting of gut tissues is not well defined. Recombinant proteins and synthetic peptides derived from HIV and SIV gp120 bind directly to integrin α4β7, a gut-homing receptor. Using both cell-surface expressed α4β7and a soluble α4β7heterodimer we demonstrate that its specific affinity for gp120 is similar to its affinity for MAdCAM (its natural ligand). The gp120 V2 domain preferentially engages extended forms of α4β7in a cation -sensitive manner and is inhibited by soluble MAdCAM. Thus, V2 mimics MAdCAM in the way that it binds to α4β7, providing HIV a potential mechanism to discriminate between functionally distinct subsets of lymphocytes, including those with gut-homing potential. Furthermore, α4β7antagonists developed for the treatment of inflammatory bowel diseases, block V2 binding to α4β7. A 15-amino acid V2 -derived peptide is sufficient to mediate binding to α4β7. It includes the canonical LDV/I α4β7binding site, a cryptic epitope that lies 7–9 amino acids amino terminal to the LDV/I, and residues K169 and I181. These two residues were identified in a sieve analysis of the RV144 vaccine trial as sites of vaccine -mediated immune pressure. HIV and SIV V2 mAbs elicited by both vaccination and infection that recognize this peptide block V2-α4β7interactions. These mAbs recognize conformations absent from the β- barrel presented in a stabilized HIV SOSIP gp120/41 trimer. The mimicry of MAdCAM-α4β7interactions by V2 may influence early events in HIV infection, particularly the rapid seeding of gut tissues, and supports the view that HIV replication in gut tissue is a central feature of HIV pathogenesis.

Original languageEnglish (US)
Article numbere1007278
JournalPLoS pathogens
Issue number8
StatePublished - Aug 2018
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology


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