HIV-1 pathogenesis differs in rectosigmoid and tonsillar tissues infected ex vivo with CCR5- and CXCR4-tropic HIV-1

Jean-Charles B. Grivel, Julie Elliott, Andrea Lisco, Angèlique Biancotto, Cristian Condack, Robin J. Shattock, Ian McGowan, Leonid Margolis, Peter Anton

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Gut-associated lymphoid tissue (GALT) has been identified as the primary target of HIV-1 infection. To investigate why GALT is especially vulnerable to HIV-1, and to determine whether the selective transmission of CCR5-using viral variants (R5) in vivo is the result of a greater susceptibility of GALT to this viral variant, we performed comparative studies of CXCR4-using (X4) and R5 HIV-1 infections of human lymphoid (tonsillar) and rectosigmoid tissues ex vivo under controlled laboratory conditions. We found that the relative level of R5 replication in rectosigmoid tissue is much greater than in tonsillar tissue. This difference is associated with the expression of the CCR5 co-receptor on approximately 70% of CD4 T cells in rectosigmoid tissue, whereas in tonsillar tissue it is expressed on fewer than 15% of CD4 T cells. Furthermore, tonsillar tissue responds to X4 HIV-1 infection by upregulating the secretion of CC-chemokines, providing a potential CCR5 blockade and further resistance to R5 infection, whereas gut tissue failed to increase such innate immune responses. Our results show that rectosigmoid tissue is more prone than tonsillar lymphoid tissue to R5 HIV-1 infection, primarily because of the high prevalence and availability of R5 cell targets and reduced chemokine blockade. The majority of CD4 T cells express CXCR4, however, and X4 HIV-1 readily replicates in both tissues, suggesting that although the differential expression of co-receptors contributes to the GALT vulnerability to R5 HIV-1, it alone cannot account for the selective R5 infection of the rectal mucosa in vivo.

Original languageEnglish
Pages (from-to)1263-1272
Number of pages10
JournalAIDS
Volume21
Issue number10
DOIs
Publication statusPublished - Jun 2007
Externally publishedYes

Fingerprint

HIV-1
Lymphoid Tissue
HIV Infections
T-Lymphocytes
CCR5 Receptors
CC Chemokines
Infection
Chemokines
Innate Immunity
Mucous Membrane

Keywords

  • Co-receptor
  • Gut-associated lymphoid tissue
  • HIV-1
  • Mucosa
  • Tonsil

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

HIV-1 pathogenesis differs in rectosigmoid and tonsillar tissues infected ex vivo with CCR5- and CXCR4-tropic HIV-1. / Grivel, Jean-Charles B.; Elliott, Julie; Lisco, Andrea; Biancotto, Angèlique; Condack, Cristian; Shattock, Robin J.; McGowan, Ian; Margolis, Leonid; Anton, Peter.

In: AIDS, Vol. 21, No. 10, 06.2007, p. 1263-1272.

Research output: Contribution to journalArticle

Grivel, J-CB, Elliott, J, Lisco, A, Biancotto, A, Condack, C, Shattock, RJ, McGowan, I, Margolis, L & Anton, P 2007, 'HIV-1 pathogenesis differs in rectosigmoid and tonsillar tissues infected ex vivo with CCR5- and CXCR4-tropic HIV-1', AIDS, vol. 21, no. 10, pp. 1263-1272. https://doi.org/10.1097/QAD.0b013e3281864667
Grivel, Jean-Charles B. ; Elliott, Julie ; Lisco, Andrea ; Biancotto, Angèlique ; Condack, Cristian ; Shattock, Robin J. ; McGowan, Ian ; Margolis, Leonid ; Anton, Peter. / HIV-1 pathogenesis differs in rectosigmoid and tonsillar tissues infected ex vivo with CCR5- and CXCR4-tropic HIV-1. In: AIDS. 2007 ; Vol. 21, No. 10. pp. 1263-1272.
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abstract = "Gut-associated lymphoid tissue (GALT) has been identified as the primary target of HIV-1 infection. To investigate why GALT is especially vulnerable to HIV-1, and to determine whether the selective transmission of CCR5-using viral variants (R5) in vivo is the result of a greater susceptibility of GALT to this viral variant, we performed comparative studies of CXCR4-using (X4) and R5 HIV-1 infections of human lymphoid (tonsillar) and rectosigmoid tissues ex vivo under controlled laboratory conditions. We found that the relative level of R5 replication in rectosigmoid tissue is much greater than in tonsillar tissue. This difference is associated with the expression of the CCR5 co-receptor on approximately 70{\%} of CD4 T cells in rectosigmoid tissue, whereas in tonsillar tissue it is expressed on fewer than 15{\%} of CD4 T cells. Furthermore, tonsillar tissue responds to X4 HIV-1 infection by upregulating the secretion of CC-chemokines, providing a potential CCR5 blockade and further resistance to R5 infection, whereas gut tissue failed to increase such innate immune responses. Our results show that rectosigmoid tissue is more prone than tonsillar lymphoid tissue to R5 HIV-1 infection, primarily because of the high prevalence and availability of R5 cell targets and reduced chemokine blockade. The majority of CD4 T cells express CXCR4, however, and X4 HIV-1 readily replicates in both tissues, suggesting that although the differential expression of co-receptors contributes to the GALT vulnerability to R5 HIV-1, it alone cannot account for the selective R5 infection of the rectal mucosa in vivo.",
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AU - McGowan, Ian

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AU - Anton, Peter

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