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131 The Role of Chitinase 3-Like-1 in the Pathological Deposition of Collagen in Lymphatic Tissue During HIV-1 Infection

Smith, A J; Zeng, M; Schacker, T W; Reilly, C S; Haase, A T

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 53
doi: 10.1097/01.qai.0000397318.55330.8c
Abstracts
Free

University of Minnesota

Background: One pathological hallmark of HIV-1 infection is the aberrant deposition of collagen and consequent fibrotic damage in both gut and lymphatic tissue, a process which adversely affects the maintenance and preservation of CD4+ T cells and overall immune function in this anatomical niche. To date, mechanistic information is still needed to account for this fibrotic process during HIV-1 infection. We recently identified a gene encoding chitinase 3-like-1 (CHI3L1) in microarray studies of HIV-1 infection in lymphatic tissues and show here that CHI3L1 may play an important role in accelerating collagen deposition during HIV-1 infection.

Methods: In vivo expression of CHI3L1 was observed using CHI3L1-specific antibodies in immunofluorescent analyses of inguinal lymph node (LN) biopsies (n = 24) from HIV-1-infected individuals at various stages of disease. The ability of CHI3L1 to participate in collagen deposition was assayed ex vivo by culturing human stromal cells in the presence or absence of recombinant human CHI3L1 and then measuring collagen type I (COL1) production via immunofluorescence and quantitative ELISA. In vivo correlation analyses were performed using Pearson's correlation coefficient (r).

Results: CHI3L1 is upregulated in the LN∼4-fold in acute HIV-1 infection, ∼3-fold in the asymptomatic stage, and ∼6-fold in AIDS compared to uninfected controls (n=4). CHI3L1 is expressed as an extracellular membrane protein predominantly in vimentin+ stromal cells/fibroblasts, and its expression mirrored COL1 deposition in vivo (r=0.8). Recombinant CHI3L1 increased COL1 synthesis∼2-fold in primary human stromal cells/fibroblasts, leading to acellular deposition of COL1; CHI3L1-specific antibodies blocked this effect.

Conclusion: Collectively, this data provides mechanistic insight surrounding aberrant collagen deposition during HIV-1 infection. CHI3L1's expression in the LN may serve to accelerate the fibrotic process during viral infection, advocating continued research in this area to develop novel therapeutic targets to attenuate pathological collagen deposition in HIV-1 infection.

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