Functional Genomic Analysis of the Response of HIV-1-Infected Lymphatic Tissue to Antiretroviral Therapy

Qingsheng Li, Timothy Schacker, John Carlis, Gregory Beilman, Phuong Nguyen, Ashley T. Haase

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Highly active antiretroviral therapy (HAART) curtails human immunodeficiency virus type 1 (HIV-1) replication in lymphatic tissues and partially reverses the pathological damage associated with infection, but the genes that mediate these pathological and reparative processes remain largely unknown. To identify these genes, we used microarrays to profile gene expression in serial lymph node biopsy specimens obtained before and after treatment. We discovered ∼200 treatment-responsive genes, many of them known mediators and moderators of immune activation and defenses, particularly innate defense genes, which, surprisingly, were expressed at all stages of HIV-1 infection. Most of the rest of the treatment-responsive genes we categorized as mediators of trafficking, reformation of active follicles, and tissue repair. We propose a model in which nearly counterbalanced functions of mediators and moderators of immune activation and defenses account for the slow dynamics of HIV-1 infection before treatment. This model suggests that there could be a role for anti-inflammatory agents, alone or in combination with HAART, in treating HIV-1 infection by tipping this balance to mitigate pathology.

Original languageEnglish (US)
Pages (from-to)572-582
Number of pages11
JournalJournal of Infectious Diseases
Volume189
Issue number4
DOIs
Publication statusPublished - Feb 15 2004

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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