The Role of Integrin α4β7 in HIV Pathogenesis and Treatment

James Arthos, Claudia Cicala, Fatima Nawaz, Siddappa Nagadenahalli Byrareddy, Francois Villinger, Philip J. Santangelo, Aftab A. Ansari, Anthony S. Fauci

Research output: Contribution to journalReview article

8 Citations (Scopus)

Abstract

Purpose of Review: Acute HIV infection is characterized by high-level viral replication throughout the body’s lymphoid system, particularly in gut-associated lymphoid tissues resulting in damage to structural components of gut tissue. This damage is irreversible and believed to contribute to the development of immune deficiencies. Antiretroviral therapy (ART) does not restore gut structure and function. Studies in macaques point to an alternative treatment strategy that may ameliorate gut damage. Integrin α4β7 mediates the homing of lymphocytes to gut tissues. Vedolizumab, a monoclonal antibody (mAb) antagonist of α4β7, has demonstrated efficacy and has been approved for the treatment of inflammatory bowel disease in humans. Here, we describe our current knowledge, and the gaps in our understanding, of the role of α4β7 in HIV pathogenesis and treatment. Recent Findings: When administered to macaques prior to infection, a nonhuman primate analogue of vedolizumab prevents transmission of SIV. In combination with ART, this mAb facilitates durable virologic control following treatment interruption. Summary: Targeting α4β7 represents a novel therapeutic approach to prevent and treat HIV infection.

Original languageEnglish (US)
Pages (from-to)127-135
Number of pages9
JournalCurrent HIV/AIDS Reports
Volume15
Issue number2
DOIs
StatePublished - Apr 1 2018

Fingerprint

Integrins
HIV
Macaca
HIV Infections
Monoclonal Antibodies
Lymphoid Tissue
Inflammatory Bowel Diseases
Primates
Therapeutics
Lymphocytes
Infection
vedolizumab

Keywords

  • Antiretroviral therapy
  • GALT
  • HIV/SIV
  • Inflammatory bowel disease
  • Integrin αβ
  • Mucosal transmission

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Arthos, J., Cicala, C., Nawaz, F., Byrareddy, S. N., Villinger, F., Santangelo, P. J., ... Fauci, A. S. (2018). The Role of Integrin α4β7 in HIV Pathogenesis and Treatment. Current HIV/AIDS Reports, 15(2), 127-135. https://doi.org/10.1007/s11904-018-0382-3

The Role of Integrin α4β7 in HIV Pathogenesis and Treatment. / Arthos, James; Cicala, Claudia; Nawaz, Fatima; Byrareddy, Siddappa Nagadenahalli; Villinger, Francois; Santangelo, Philip J.; Ansari, Aftab A.; Fauci, Anthony S.

In: Current HIV/AIDS Reports, Vol. 15, No. 2, 01.04.2018, p. 127-135.

Research output: Contribution to journalReview article

Arthos, J, Cicala, C, Nawaz, F, Byrareddy, SN, Villinger, F, Santangelo, PJ, Ansari, AA & Fauci, AS 2018, 'The Role of Integrin α4β7 in HIV Pathogenesis and Treatment', Current HIV/AIDS Reports, vol. 15, no. 2, pp. 127-135. https://doi.org/10.1007/s11904-018-0382-3
Arthos, James ; Cicala, Claudia ; Nawaz, Fatima ; Byrareddy, Siddappa Nagadenahalli ; Villinger, Francois ; Santangelo, Philip J. ; Ansari, Aftab A. ; Fauci, Anthony S. / The Role of Integrin α4β7 in HIV Pathogenesis and Treatment. In: Current HIV/AIDS Reports. 2018 ; Vol. 15, No. 2. pp. 127-135.
@article{2769bd5efbed4d3db2fd53a32e4392f5,
title = "The Role of Integrin α4β7 in HIV Pathogenesis and Treatment",
abstract = "Purpose of Review: Acute HIV infection is characterized by high-level viral replication throughout the body’s lymphoid system, particularly in gut-associated lymphoid tissues resulting in damage to structural components of gut tissue. This damage is irreversible and believed to contribute to the development of immune deficiencies. Antiretroviral therapy (ART) does not restore gut structure and function. Studies in macaques point to an alternative treatment strategy that may ameliorate gut damage. Integrin α4β7 mediates the homing of lymphocytes to gut tissues. Vedolizumab, a monoclonal antibody (mAb) antagonist of α4β7, has demonstrated efficacy and has been approved for the treatment of inflammatory bowel disease in humans. Here, we describe our current knowledge, and the gaps in our understanding, of the role of α4β7 in HIV pathogenesis and treatment. Recent Findings: When administered to macaques prior to infection, a nonhuman primate analogue of vedolizumab prevents transmission of SIV. In combination with ART, this mAb facilitates durable virologic control following treatment interruption. Summary: Targeting α4β7 represents a novel therapeutic approach to prevent and treat HIV infection.",
keywords = "Antiretroviral therapy, GALT, HIV/SIV, Inflammatory bowel disease, Integrin αβ, Mucosal transmission",
author = "James Arthos and Claudia Cicala and Fatima Nawaz and Byrareddy, {Siddappa Nagadenahalli} and Francois Villinger and Santangelo, {Philip J.} and Ansari, {Aftab A.} and Fauci, {Anthony S.}",
year = "2018",
month = "4",
day = "1",
doi = "10.1007/s11904-018-0382-3",
language = "English (US)",
volume = "15",
pages = "127--135",
journal = "Current HIV/AIDS Reports",
issn = "1548-3568",
number = "2",

}

TY - JOUR

T1 - The Role of Integrin α4β7 in HIV Pathogenesis and Treatment

AU - Arthos, James

AU - Cicala, Claudia

AU - Nawaz, Fatima

AU - Byrareddy, Siddappa Nagadenahalli

AU - Villinger, Francois

AU - Santangelo, Philip J.

AU - Ansari, Aftab A.

AU - Fauci, Anthony S.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Purpose of Review: Acute HIV infection is characterized by high-level viral replication throughout the body’s lymphoid system, particularly in gut-associated lymphoid tissues resulting in damage to structural components of gut tissue. This damage is irreversible and believed to contribute to the development of immune deficiencies. Antiretroviral therapy (ART) does not restore gut structure and function. Studies in macaques point to an alternative treatment strategy that may ameliorate gut damage. Integrin α4β7 mediates the homing of lymphocytes to gut tissues. Vedolizumab, a monoclonal antibody (mAb) antagonist of α4β7, has demonstrated efficacy and has been approved for the treatment of inflammatory bowel disease in humans. Here, we describe our current knowledge, and the gaps in our understanding, of the role of α4β7 in HIV pathogenesis and treatment. Recent Findings: When administered to macaques prior to infection, a nonhuman primate analogue of vedolizumab prevents transmission of SIV. In combination with ART, this mAb facilitates durable virologic control following treatment interruption. Summary: Targeting α4β7 represents a novel therapeutic approach to prevent and treat HIV infection.

AB - Purpose of Review: Acute HIV infection is characterized by high-level viral replication throughout the body’s lymphoid system, particularly in gut-associated lymphoid tissues resulting in damage to structural components of gut tissue. This damage is irreversible and believed to contribute to the development of immune deficiencies. Antiretroviral therapy (ART) does not restore gut structure and function. Studies in macaques point to an alternative treatment strategy that may ameliorate gut damage. Integrin α4β7 mediates the homing of lymphocytes to gut tissues. Vedolizumab, a monoclonal antibody (mAb) antagonist of α4β7, has demonstrated efficacy and has been approved for the treatment of inflammatory bowel disease in humans. Here, we describe our current knowledge, and the gaps in our understanding, of the role of α4β7 in HIV pathogenesis and treatment. Recent Findings: When administered to macaques prior to infection, a nonhuman primate analogue of vedolizumab prevents transmission of SIV. In combination with ART, this mAb facilitates durable virologic control following treatment interruption. Summary: Targeting α4β7 represents a novel therapeutic approach to prevent and treat HIV infection.

KW - Antiretroviral therapy

KW - GALT

KW - HIV/SIV

KW - Inflammatory bowel disease

KW - Integrin αβ

KW - Mucosal transmission

UR - http://www.scopus.com/inward/record.url?scp=85042458414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042458414&partnerID=8YFLogxK

U2 - 10.1007/s11904-018-0382-3

DO - 10.1007/s11904-018-0382-3

M3 - Review article

C2 - 29478152

AN - SCOPUS:85042458414

VL - 15

SP - 127

EP - 135

JO - Current HIV/AIDS Reports

JF - Current HIV/AIDS Reports

SN - 1548-3568

IS - 2

ER -