Therapy of 'SHIV' infected macaques with liposomes delivering antisense interleukin-4 DNA

Navneet K. Dhillon, Sukhbir Dhillon, Yahia Chebloune, David Pinson, Francois Villinger, Anil Kumar, Opendra Narayan, Shilpa Buch

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3 Scopus citations

Abstract

Background/objectives: To explore the effects of antisense (AS) interleukin (IL)-4 on virus replication and CD8+ T-cell responses in lymph nodes and blood of macaques infected with simian human immunodeficiency virus, SHIV89.6P. Methods: Six macaques were inoculated with simian human immunodeficiency virus (SHIV89.6P). Seven days later, four of the animals were given 1 mg AS IL-4 plasmid complexed with Megafectin liposome, intravenously, and two of these received a second injection of the same material on day 9. All six macaques were killed at 2 weeks post infection (pi) and monitored for viral RNA and CD8+ T cells in blood and lymph nodes by real-time reverse transcriptase-polymerase chain reaction, flow cytometry and immunohistochemistry. Results: In contrast to the lymph nodes from virus control animals, the lymph nodes of AS IL-4-treated animals had a significant reduction in viral loads and reduced depletion of cells from the nodes. There was an increase in CD8+ T cells in the nodes, and many of the cells expressed granzyme B, suggesting functional activation. This trend of virus reduction and increased CD8+ T cell numbers was also reflected in blood. Conclusions: The therapeutic effect of the AS IL-4 suggests indirectly that the acute immunosuppressive disease caused by SHIVs is mediated, in part, by IL-4 that causes enhanced virus replication by suppressing anti-viral CD8+ T-cell responses, and that this effect was reduced by treatment of the animals with AS IL-4.

Original languageEnglish (US)
Pages (from-to)1125-1130
Number of pages6
JournalAIDS
Volume20
Issue number8
DOIs
StatePublished - May 1 2006

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Keywords

  • AIDS
  • Antisense DNA
  • CD8 T cells
  • Interleukin-4
  • Macaques
  • SHIVP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Dhillon, N. K., Dhillon, S., Chebloune, Y., Pinson, D., Villinger, F., Kumar, A., Narayan, O., & Buch, S. (2006). Therapy of 'SHIV' infected macaques with liposomes delivering antisense interleukin-4 DNA. AIDS, 20(8), 1125-1130. https://doi.org/10.1097/01.aids.0000226952.49353.36