Inhibitory and enhancing effects of IFN-γ and IL-4 on SHIVKU replication in rhesus macaque macrophages: Correlation between TH2 cytokines and productive infection in tissue macrophages during late-stage infection

Shilpa Buch, David Pinson, Christopher L. King, Ravi Raghavan, Yueping Hou, Zhuang Li, Istvan Adany, Andre Hicks, Francois Villinger, Anil Kumar, Opendra Narayan

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

HIV-1 is dual-tropic for CD4+ T lymphocytes and macrophages, but virus production in the macrophages becomes manifest only during late-stage infection, after CD4+ T cell functions are lost, and when opportunistic pathogens begin to flourish. In this study, the SHIV/macaque model of HIV pathogenesis was used to assess the role of cytokines in regulating virus replication in the two cell types. We injected complete Freund's adjuvant (CFA) intradermally into SHIVKU-infected macaques, and infused Schistosoma mansoni eggs into the liver and lungs of others. Tissues examined from these animals demonstrated that macrophages induced by CFA did not support viral replication while those induced by S. mansoni eggs had evidence of productive infection. RT-PCR analysis showed that both Th1 (IL-2 and IFN-γ) and Th2 cytokines (IL-4 and IL-10) were present in the CFA lesions but only the Th2 cytokines were found in the S. mansoni lesions. Follow-up studies in macaque cell cultures showed that whereas IFN-γ caused enhancement of virus replication in CD4+ T cells, it curtailed viral replication in infected macrophages. In contrast, IL-4 enhanced viral replication in infected macrophages. These studies strongly suggest that cytokines regulate the sequential phases of HIV replication in CD4 T cells and macrophages.

Original languageEnglish (US)
Pages (from-to)295-304
Number of pages10
JournalCytokine
Volume13
Issue number5
DOIs
StatePublished - Mar 7 2001

Fingerprint

Macrophages
Macaca mulatta
Interleukin-4
T-cells
Tissue
Cytokines
Schistosoma mansoni
Freund's Adjuvant
Macaca
Infection
Viruses
T-Lymphocytes
Virus Replication
Eggs
HIV
Tropics
Pathogens
Cell culture
Liver
Interleukin-10

Keywords

  • AIDS
  • HIV
  • SHIV
  • Th-Th cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

Inhibitory and enhancing effects of IFN-γ and IL-4 on SHIVKU replication in rhesus macaque macrophages : Correlation between TH2 cytokines and productive infection in tissue macrophages during late-stage infection. / Buch, Shilpa; Pinson, David; King, Christopher L.; Raghavan, Ravi; Hou, Yueping; Li, Zhuang; Adany, Istvan; Hicks, Andre; Villinger, Francois; Kumar, Anil; Narayan, Opendra.

In: Cytokine, Vol. 13, No. 5, 07.03.2001, p. 295-304.

Research output: Contribution to journalArticle

Buch, Shilpa ; Pinson, David ; King, Christopher L. ; Raghavan, Ravi ; Hou, Yueping ; Li, Zhuang ; Adany, Istvan ; Hicks, Andre ; Villinger, Francois ; Kumar, Anil ; Narayan, Opendra. / Inhibitory and enhancing effects of IFN-γ and IL-4 on SHIVKU replication in rhesus macaque macrophages : Correlation between TH2 cytokines and productive infection in tissue macrophages during late-stage infection. In: Cytokine. 2001 ; Vol. 13, No. 5. pp. 295-304.
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