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Constitutive expression of stromal derived factor-1 by mucosal epithelia and its role in HIV transmission and propagation

Agace, William LU ; Amara, A ; Roberts, A I ; Pablos, J L ; Thelen, S ; Uguccioni, M ; Li, X Y ; Marsal, J ; Arenzana-Seisdedos, F and Delaunay, T , et al. (2000) In Current Biology 10(6). p.325-328
Abstract
HIV particles that use the chemokine receptor CXCR4 as a coreceptor for entry into cells (X4-HIV) inefficiently transmit infection across mucosal surfaces [1], despite their presence in seminal fluid and mucosal secretions from infected individuals [2] [3] [4]. In addition, although intestinal lymphocytes are susceptible to infection with either X4-HIV particles or particles that use the chemokine receptor CCR5 for viral entry (R5-HIV) during ex vivo culture [5], only systemic inoculation of R5-chimeric simian-HIV (S-HIV) results in a rapid loss of CD4(+) intestinal lymphocytes in macaques [6]. The mechanisms underlying the inefficient capacity of X4-HIV to transmit infection across mucosal surfaces and to infect intestinal lymphocytes in... (More)
HIV particles that use the chemokine receptor CXCR4 as a coreceptor for entry into cells (X4-HIV) inefficiently transmit infection across mucosal surfaces [1], despite their presence in seminal fluid and mucosal secretions from infected individuals [2] [3] [4]. In addition, although intestinal lymphocytes are susceptible to infection with either X4-HIV particles or particles that use the chemokine receptor CCR5 for viral entry (R5-HIV) during ex vivo culture [5], only systemic inoculation of R5-chimeric simian-HIV (S-HIV) results in a rapid loss of CD4(+) intestinal lymphocytes in macaques [6]. The mechanisms underlying the inefficient capacity of X4-HIV to transmit infection across mucosal surfaces and to infect intestinal lymphocytes in vivo have remained elusive. The CCR5 ligands RANTES, MIP-1alpha and MIP-1beta suppress infection by R5-HIV-1 particles via induction of CCR5 internalization, and individuals whose peripheral blood lymphocytes produce high levels of these chemokines are relatively resistant to infection [7] [8] [9]. Here, we show that the CXCR4 ligand stromal derived factor-1 (SDF-1) is constitutively expressed by mucosal epithelial cells at sites of HIV transmission and propagation. Furthermore, CXCR4 is selectively downmodulated on intestinal lymphocytes within the setting of prominent SDF-1 expression. We postulate that mucosally derived SDF-1 continuously downmodulates CXCR4 on resident HIV target cells, thereby reducing the transmission and propagation of X4-HIV at mucosal sites. Moreover, such a mechanism could contribute to the delayed emergence of X4 isolates, which predominantly occurs during the later stages of the HIV infection. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Current Biology
volume
10
issue
6
pages
325 - 328
publisher
Elsevier
external identifiers
  • pmid:10744978
  • scopus:0034704853
ISSN
1879-0445
language
English
LU publication?
no
id
2f1c638f-2b78-494a-92c8-5f50f3a7838f (old id 1116347)
alternative location
http://download.current-biology.com/pdfs/0960-9822/PIIS0960982200003808.pdf
date added to LUP
2016-04-01 12:25:50
date last changed
2023-09-18 13:38:48
@article{2f1c638f-2b78-494a-92c8-5f50f3a7838f,
  abstract     = {{HIV particles that use the chemokine receptor CXCR4 as a coreceptor for entry into cells (X4-HIV) inefficiently transmit infection across mucosal surfaces [1], despite their presence in seminal fluid and mucosal secretions from infected individuals [2] [3] [4]. In addition, although intestinal lymphocytes are susceptible to infection with either X4-HIV particles or particles that use the chemokine receptor CCR5 for viral entry (R5-HIV) during ex vivo culture [5], only systemic inoculation of R5-chimeric simian-HIV (S-HIV) results in a rapid loss of CD4(+) intestinal lymphocytes in macaques [6]. The mechanisms underlying the inefficient capacity of X4-HIV to transmit infection across mucosal surfaces and to infect intestinal lymphocytes in vivo have remained elusive. The CCR5 ligands RANTES, MIP-1alpha and MIP-1beta suppress infection by R5-HIV-1 particles via induction of CCR5 internalization, and individuals whose peripheral blood lymphocytes produce high levels of these chemokines are relatively resistant to infection [7] [8] [9]. Here, we show that the CXCR4 ligand stromal derived factor-1 (SDF-1) is constitutively expressed by mucosal epithelial cells at sites of HIV transmission and propagation. Furthermore, CXCR4 is selectively downmodulated on intestinal lymphocytes within the setting of prominent SDF-1 expression. We postulate that mucosally derived SDF-1 continuously downmodulates CXCR4 on resident HIV target cells, thereby reducing the transmission and propagation of X4-HIV at mucosal sites. Moreover, such a mechanism could contribute to the delayed emergence of X4 isolates, which predominantly occurs during the later stages of the HIV infection.}},
  author       = {{Agace, William and Amara, A and Roberts, A I and Pablos, J L and Thelen, S and Uguccioni, M and Li, X Y and Marsal, J and Arenzana-Seisdedos, F and Delaunay, T and Ebert, E C and Moser, B and Parker, C M}},
  issn         = {{1879-0445}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{325--328}},
  publisher    = {{Elsevier}},
  series       = {{Current Biology}},
  title        = {{Constitutive expression of stromal derived factor-1 by mucosal epithelia and its role in HIV transmission and propagation}},
  url          = {{http://download.current-biology.com/pdfs/0960-9822/PIIS0960982200003808.pdf}},
  volume       = {{10}},
  year         = {{2000}},
}