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講演者: Dr. Andrew Lackner&s_comma; Director&s_comma; Tulane National Primate Research Center

演題名: " Neuropathogensis of AIDS: insights from the nonhuman primate model "

日 時: 平成19年12月10日(月) 午後4時30分~6時30分

場 所: 国立感染症研究所 共用第2会議室


Infection of the central nervous system by SIV/HIV primarily involves cells of
monocyte/macrophage lineage. The primary targets of productive SIV/HIV infection are
perivascular macrophages&s_comma; which are normally replaced by circulating monocytes.
Perivascular macrophages are in intimate contact with brain microvascular endothelial
cells and together with astrocytes and microglial foot processes constitute the blood
brain barrier. During HIV/SIV infection there is systemic activation of circulating
monocytes that likely increases their ability to cross the blood brain barrier
accelerating normal trafficking. Some of these cells are infected and carry the virus
into the brain within days of infection. As the monocytes differentiate into
macrophages they become a better substrate for viral replication and produce a variety
of cytokines and chemokines. The cytokines and chemokines cause activation of various
other cell types in the brain including endothelial cells&s_comma; microglia and astrocytes.
The endothelial cells upgregulate adhesion molecules&s_comma; which along with increased
chemokine production facilitates further recruitment of leukocyte (primarily
monocyte/macrophages) into the brain&s_comma; giving rise to perivascular cuffs. Most of the
cells in these cuffs are not infected by HIV/SIV but likely serve as fodder for further
rounds of viral replication. Multinucleated giant cells&s_comma; which are a histologic
hallmark of SIV and HIV encephalitis result from the fusion of infected and uninfected
perivascular macrophages as well as other monocyte/macrophage lineage cells such as
microglia. The activation of astrocytes&s_comma; microglia and possibly neurons via cytokines
and chemokines as well as production of a variety of potential viral or host-derived
neurotoxins from macrophages in the CNS are thought to lead to neuronal damage.
(References: Annu Rev Med. 2007;58:461-76. Review&s_comma; PLoS Med. 2006 Dec 5;3(12)&s_comma; Blood.
2007 Feb 1;109(3):1069-76&s_comma; Blood. 2007 Feb 1;109(3):1174-81 &s_comma;Science. 2006

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