Functional genomic analysis of the response of HIV-1-infected lymphatic tissue to antiretroviral therapy.
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 approximately 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.
Li
Qingsheng
Q
Department of Microbiology, Department of Medicine, University of Minnesota Medical School, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Schacker
Timothy
T
Carlis
John
J
Beilman
Gregory
G
Nguyen
Phuong
P
Haase
Ashley T
AT
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001706:Biopsy; D017931:DNA Primers; D023281:Genomics; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D008198:Lymph Nodes / Q000473:pathology*; D008221:Lymphoid Tissue / Q000187:drug effects / Q000473:pathology / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification
D019380:Anti-HIV Agents; D017931:DNA Primers; D012367:RNA, Viral