Integrin α4β7 Expression Increases HIV Susceptibility in Activated Cervical CD4 + T Cells by an HIV Attachment-Independent Mechanism

Jian Ding, Carley Tasker, Pierre Lespinasse, Jihong Dai, Patricia Fitzgerald-Bocarsly, Wuyuan Lu, Debra Heller, Theresa Li Yun Chang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: CD4 + T cells are crucial for the establishment and dissemination of HIV in mucosal tissues during acute infection. Studies indicate that integrin α4β7 + CD4 + T cells are preferentially infected by HIV in vitro and during acute SIV infection. The integrin α4β7 is thought to promote HIV capture by target cells; however, the role of integrin α4β7 in HIV transmission remains controversial. In this study, we characterized immune phenotypes of human cervical T cells and examined HIV preference in integrin α4β7 + CD4 + T cells. In vitro all-trans retinoic acid-differentiated peripheral CD4 + T cells (atRA-differentiated cells) were included as a comparison. Results: In both peripheral and cervical cells, the majority of HIV p24 + cells were activated CD4 + T cells expressing integrin α4β7. Among infected atRA-differentiated cells, the frequency of CCR5 expression was higher in HIV p24 + cells than in HIV p24-cells; no such difference was observed in cervical cells. Neither the cyclic hexapeptide CWLDVC nor a monoclonal antibody against integrin α4β7 blocked HIV attachment or gp120 binding to target cells regardless of the presence of CD4, indicating that integrin α4β7 did not facilitate HIV capture by target cells. Conclusions: Integrin α4β7 expression increases HIV susceptibility, but the mechanism is not through promoting HIV binding to target cells.

Original languageEnglish (US)
Pages (from-to)509-518
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume69
Issue number5
DOIs
StatePublished - Aug 15 2015

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Integrins
HIV
T-Lymphocytes
HIV Core Protein p24
Tretinoin
Infection
Mucous Membrane
Monoclonal Antibodies
Phenotype

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Pharmacology (medical)

Keywords

  • HIV attachment
  • HIV susceptibility
  • cervical CD4 + T cells
  • integrin α4β7

Cite this

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title = "Integrin α4β7 Expression Increases HIV Susceptibility in Activated Cervical CD4 + T Cells by an HIV Attachment-Independent Mechanism",
abstract = "Background: CD4 + T cells are crucial for the establishment and dissemination of HIV in mucosal tissues during acute infection. Studies indicate that integrin α4β7 + CD4 + T cells are preferentially infected by HIV in vitro and during acute SIV infection. The integrin α4β7 is thought to promote HIV capture by target cells; however, the role of integrin α4β7 in HIV transmission remains controversial. In this study, we characterized immune phenotypes of human cervical T cells and examined HIV preference in integrin α4β7 + CD4 + T cells. In vitro all-trans retinoic acid-differentiated peripheral CD4 + T cells (atRA-differentiated cells) were included as a comparison. Results: In both peripheral and cervical cells, the majority of HIV p24 + cells were activated CD4 + T cells expressing integrin α4β7. Among infected atRA-differentiated cells, the frequency of CCR5 expression was higher in HIV p24 + cells than in HIV p24-cells; no such difference was observed in cervical cells. Neither the cyclic hexapeptide CWLDVC nor a monoclonal antibody against integrin α4β7 blocked HIV attachment or gp120 binding to target cells regardless of the presence of CD4, indicating that integrin α4β7 did not facilitate HIV capture by target cells. Conclusions: Integrin α4β7 expression increases HIV susceptibility, but the mechanism is not through promoting HIV binding to target cells.",
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Integrin α4β7 Expression Increases HIV Susceptibility in Activated Cervical CD4 + T Cells by an HIV Attachment-Independent Mechanism. / Ding, Jian; Tasker, Carley; Lespinasse, Pierre; Dai, Jihong; Fitzgerald-Bocarsly, Patricia; Lu, Wuyuan; Heller, Debra; Chang, Theresa Li Yun.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 69, No. 5, 15.08.2015, p. 509-518.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Integrin α4β7 Expression Increases HIV Susceptibility in Activated Cervical CD4 + T Cells by an HIV Attachment-Independent Mechanism

AU - Ding, Jian

AU - Tasker, Carley

AU - Lespinasse, Pierre

AU - Dai, Jihong

AU - Fitzgerald-Bocarsly, Patricia

AU - Lu, Wuyuan

AU - Heller, Debra

AU - Chang, Theresa Li Yun

PY - 2015/8/15

Y1 - 2015/8/15

N2 - Background: CD4 + T cells are crucial for the establishment and dissemination of HIV in mucosal tissues during acute infection. Studies indicate that integrin α4β7 + CD4 + T cells are preferentially infected by HIV in vitro and during acute SIV infection. The integrin α4β7 is thought to promote HIV capture by target cells; however, the role of integrin α4β7 in HIV transmission remains controversial. In this study, we characterized immune phenotypes of human cervical T cells and examined HIV preference in integrin α4β7 + CD4 + T cells. In vitro all-trans retinoic acid-differentiated peripheral CD4 + T cells (atRA-differentiated cells) were included as a comparison. Results: In both peripheral and cervical cells, the majority of HIV p24 + cells were activated CD4 + T cells expressing integrin α4β7. Among infected atRA-differentiated cells, the frequency of CCR5 expression was higher in HIV p24 + cells than in HIV p24-cells; no such difference was observed in cervical cells. Neither the cyclic hexapeptide CWLDVC nor a monoclonal antibody against integrin α4β7 blocked HIV attachment or gp120 binding to target cells regardless of the presence of CD4, indicating that integrin α4β7 did not facilitate HIV capture by target cells. Conclusions: Integrin α4β7 expression increases HIV susceptibility, but the mechanism is not through promoting HIV binding to target cells.

AB - Background: CD4 + T cells are crucial for the establishment and dissemination of HIV in mucosal tissues during acute infection. Studies indicate that integrin α4β7 + CD4 + T cells are preferentially infected by HIV in vitro and during acute SIV infection. The integrin α4β7 is thought to promote HIV capture by target cells; however, the role of integrin α4β7 in HIV transmission remains controversial. In this study, we characterized immune phenotypes of human cervical T cells and examined HIV preference in integrin α4β7 + CD4 + T cells. In vitro all-trans retinoic acid-differentiated peripheral CD4 + T cells (atRA-differentiated cells) were included as a comparison. Results: In both peripheral and cervical cells, the majority of HIV p24 + cells were activated CD4 + T cells expressing integrin α4β7. Among infected atRA-differentiated cells, the frequency of CCR5 expression was higher in HIV p24 + cells than in HIV p24-cells; no such difference was observed in cervical cells. Neither the cyclic hexapeptide CWLDVC nor a monoclonal antibody against integrin α4β7 blocked HIV attachment or gp120 binding to target cells regardless of the presence of CD4, indicating that integrin α4β7 did not facilitate HIV capture by target cells. Conclusions: Integrin α4β7 expression increases HIV susceptibility, but the mechanism is not through promoting HIV binding to target cells.

KW - HIV attachment

KW - HIV susceptibility

KW - cervical CD4 + T cells

KW - integrin α4β7

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