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1、C101 VIRAL PATHOGENESIS AND IMMUNITY / Poster Discussion / Tuesday, May 19/1:30 PM4:00 PM / Room 15 AB (Mezzanine Level) San Diego Convention Center Persistent Immune Activation and Macrophage Accumulation in SARSCoronavirus Infection. C. C. Clay 1, N. J. Donart1, N. G. Fomukong1, J. B. Knight1, S.
2、K. Kunder1, B. Li1, K. A. Overheim1 and K. S. Harrod1. Email: cclaylrri.org 1Lovelace Respiratory Research Institute, Albuquerque, NM. Damage to the lung in SARSCoV infection has been attributed to the direct viral destruction of respiratory epithelium as well as excessive inflammatory responses tri
3、ggered by the virus. However, the relative contribution of these mechanisms to SARS remains controversial. Furthermore, the phenotypic identification of immune cells involved in early SARSCoVmediated inflammation has not been elucidated, in part due to the lack of a useful animal model. Our recently
4、 developed nonhuman primate model is uniquely suited for systematic examination of the timing and extent of lung inflammation to improve our understanding of SARSCoV immunopathogenesis. In African Green monkeys intranasallyinfected with SARSCoV, lung viral load levels peak early, between days 1 and
5、5 post infection (p.i.). Pathological changes consistent with interstitial pneumonia, follow the peak in viral replication and extend beyond active viral infection. Gross pulmonary lesions and histological evidence of interstitial pneumonia are not apparent until after day 10 p.i. Flow cytometric an
6、alysis of inflamed lung tissue reveals that monocytes/macrophages increase in frequency and in the level of activation as compared to the total leukocytes in the lung. Areas of activated monocyte/macrophage accumulation persist in SARSCoV infected animals and can be detected out to day 28 p.i. In ad
7、dition, inflammatory cytokines IL15 and IL18, which are predominantly produced by monocytes/macrophages remain elevated until day 21 in SARSCoV infection. These findings suggest that SARSCoV triggers prolonged immune activation in the lung and that monocytes/macrophages play a prominent role in the immunopathogenesis of SARSCoV infection. This abstract is funded by: NIH contract N01AI40095. Am J Respir Crit Care Med 179;2009:A5170 Internet address: www.atsjournals.orgOnline Abstracts Issue
