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 Nagadenahalli Byrareddy, Philip J. Santangelo, Lynn Morris, Constantinos Kurt Wibmer & 15 others Kristin 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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

HIV Infections
Vaccination
HIV
HIV Envelope Protein gp120
Antibodies
Peptides
Vaccines
Amino Acids
Lymphocyte Subsets
Inflammatory Bowel Diseases
Recombinant Proteins
Integrins
Gastrointestinal Tract
Cations
HIV-1
Epitopes
Ligands
Pressure
Infection
Therapeutics

ASJC Scopus subject areas

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

Cite this

Select gp120 V2 domain specific antibodies derived from HIV and SIV infection and vaccination inhibit gp120 binding to α4β7 . / Lertjuthaporn, Sakaorat; Cicala, Claudia; Van Ryk, Donald; Liu, Matthew; Yolitz, Jason; Wei, Danlan; Nawaz, Fatima; Doyle, Allison; Horowitch, Brooke; Park, Chung; Lu, Shan; Lou, Yang; Wang, Shixia; Pan, Ruimin; Jiang, Xunqing; Villinger, Francois; Byrareddy, Siddappa Nagadenahalli; Santangelo, Philip J.; Morris, Lynn; Wibmer, Constantinos Kurt; Biris, Kristin; Mason, Rosemarie D.; Gorman, Jason; Hiatt, Joseph; Martinelli, Elena; Roederer, Mario; Fujikawa, Dai; Gorini, Giacomo; Franchini, Genoveffa; Arakelyan, Anush; Ansari, Aftab A.; Pattanapanyasat, Kovit; Kong, Xiang Peng; Fauci, Anthony S.; Arthos, James.

In: PLoS Pathogens, Vol. 14, No. 8, e1007278, 01.08.2018.

Research output: Contribution to journalArticle

Lertjuthaporn, S, Cicala, C, Van Ryk, D, Liu, M, Yolitz, J, Wei, D, Nawaz, F, Doyle, A, Horowitch, B, Park, C, Lu, S, Lou, Y, Wang, S, Pan, R, Jiang, X, Villinger, F, Byrareddy, SN, Santangelo, PJ, Morris, L, Wibmer, CK, Biris, K, Mason, RD, Gorman, J, Hiatt, J, Martinelli, E, Roederer, M, Fujikawa, D, Gorini, G, Franchini, G, Arakelyan, A, Ansari, AA, Pattanapanyasat, K, Kong, XP, Fauci, AS & Arthos, J 2018, 'Select gp120 V2 domain specific antibodies derived from HIV and SIV infection and vaccination inhibit gp120 binding to α4β7 ', PLoS Pathogens, vol. 14, no. 8, e1007278. https://doi.org/10.1371/journal.ppat.1007278
Lertjuthaporn, Sakaorat ; Cicala, Claudia ; Van Ryk, Donald ; Liu, Matthew ; Yolitz, Jason ; Wei, Danlan ; Nawaz, Fatima ; Doyle, Allison ; Horowitch, Brooke ; Park, Chung ; Lu, Shan ; Lou, Yang ; Wang, Shixia ; Pan, Ruimin ; Jiang, Xunqing ; Villinger, Francois ; Byrareddy, Siddappa Nagadenahalli ; Santangelo, Philip J. ; Morris, Lynn ; Wibmer, Constantinos Kurt ; Biris, Kristin ; Mason, Rosemarie D. ; Gorman, Jason ; Hiatt, Joseph ; Martinelli, Elena ; Roederer, Mario ; Fujikawa, Dai ; Gorini, Giacomo ; Franchini, Genoveffa ; Arakelyan, Anush ; Ansari, Aftab A. ; Pattanapanyasat, Kovit ; Kong, Xiang Peng ; Fauci, Anthony S. ; Arthos, James. / Select gp120 V2 domain specific antibodies derived from HIV and SIV infection and vaccination inhibit gp120 binding to α4β7 In: PLoS Pathogens. 2018 ; Vol. 14, No. 8.
@article{98754abca58d4c17883db2342bbd2145,
title = "Select gp120 V2 domain specific antibodies derived from HIV and SIV infection and vaccination inhibit gp120 binding to α4β7",
abstract = "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.",
author = "Sakaorat Lertjuthaporn and Claudia Cicala and {Van Ryk}, Donald and Matthew Liu and Jason Yolitz and Danlan Wei and Fatima Nawaz and Allison Doyle and Brooke Horowitch and Chung Park and Shan Lu and Yang Lou and Shixia Wang and Ruimin Pan and Xunqing Jiang and Francois Villinger and Byrareddy, {Siddappa Nagadenahalli} and Santangelo, {Philip J.} and Lynn Morris and Wibmer, {Constantinos Kurt} and Kristin Biris and Mason, {Rosemarie D.} and Jason Gorman and Joseph Hiatt and Elena Martinelli and Mario Roederer and Dai Fujikawa and Giacomo Gorini and Genoveffa Franchini and Anush Arakelyan and Ansari, {Aftab A.} and Kovit Pattanapanyasat and Kong, {Xiang Peng} and Fauci, {Anthony S.} and James Arthos",
year = "2018",
month = "8",
day = "1",
doi = "10.1371/journal.ppat.1007278",
language = "English (US)",
volume = "14",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "8",

}

TY - JOUR

T1 - Select gp120 V2 domain specific antibodies derived from HIV and SIV infection and vaccination inhibit gp120 binding to α4β7

AU - Lertjuthaporn, Sakaorat

AU - Cicala, Claudia

AU - Van Ryk, Donald

AU - Liu, Matthew

AU - Yolitz, Jason

AU - Wei, Danlan

AU - Nawaz, Fatima

AU - Doyle, Allison

AU - Horowitch, Brooke

AU - Park, Chung

AU - Lu, Shan

AU - Lou, Yang

AU - Wang, Shixia

AU - Pan, Ruimin

AU - Jiang, Xunqing

AU - Villinger, Francois

AU - Byrareddy, Siddappa Nagadenahalli

AU - Santangelo, Philip J.

AU - Morris, Lynn

AU - Wibmer, Constantinos Kurt

AU - Biris, Kristin

AU - Mason, Rosemarie D.

AU - Gorman, Jason

AU - Hiatt, Joseph

AU - Martinelli, Elena

AU - Roederer, Mario

AU - Fujikawa, Dai

AU - Gorini, Giacomo

AU - Franchini, Genoveffa

AU - Arakelyan, Anush

AU - Ansari, Aftab A.

AU - Pattanapanyasat, Kovit

AU - Kong, Xiang Peng

AU - Fauci, Anthony S.

AU - Arthos, James

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85053086140&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053086140&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1007278

DO - 10.1371/journal.ppat.1007278

M3 - Article

VL - 14

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 8

M1 - e1007278

ER -