
<ArticleTitle>Interferon-independent, human immunodeficiency virus type 1 <prot>gp120</prot>-mediated induction of <prot>CXCL10</prot>/<prot>IP-10</prot> gene expression by astrocytes in vivo and in vitro.</ArticleTitle>
<AbstractText>The <prot>CXC chemokine gamma interferon (<prot>IFN-gamma</prot>)-inducible protein</prot> <prot>CXCL10</prot>/<prot>IP-10</prot> is markedly elevated in cerebrospinal fluid and brain of individuals infected with human immunodeficiency virus type 1 (HIV-1) and is implicated in the pathogenesis of HIV-associated dementia (HAD). To explore the possible role of <prot>CXCL10</prot>/<prot>IP-10</prot> in HAD, we examined the expression of this and other chemokines in the central nervous system (CNS) of transgenic mice with astrocyte-targeted expression of HIV <prot>gp120</prot> under the control of the <prot>glial fibrillary acidic protein</prot> (<prot>GFAP</prot>) promoter, a murine model for HIV-1 encephalopathy. Compared with wild-type controls, CNS expression of the CC chemokine gene <prot>CCL2</prot>/<prot>MCP-1</prot> and the CXC chemokine genes <prot>CXCL10</prot>/<prot>IP-10</prot> and <prot>CXCL9</prot>/<prot>Mig</prot> was induced in the <prot>GFAP</prot>-HIV <prot>gp120</prot> mice. <prot>CXCL10</prot>/<prot>IP-10</prot> RNA expression was increased most and overlapped the expression of the transgene-encoded HIV <prot>gp120</prot> gene. Astrocytes and to a lesser extent microglia were identified as the major cellular sites for <prot>CXCL10</prot>/<prot>IP-10</prot> gene expression. There was no detectable expression of any class of IFN or their responsive genes. In astrocyte cultures, soluble recombinant HIV <prot>gp120</prot> protein was capable of directly inducing <prot>CXCL10</prot>/<prot>IP-10</prot> gene expression a process that was independent of <prot>STAT1</prot>. These findings highlight a novel IFN- and <prot>STAT1</prot>-independent mechanism for the regulation of <prot>CXCL10</prot>/<prot>IP-10</prot> expression and directly link expression of HIV <prot>gp120</prot> to the induction of <prot>CXCL10</prot>/<prot>IP-10</prot> that is found in HIV infection of the CNS. Finally, one function of <prot>IP-10</prot> expression may be the recruitment of leukocytes to the CNS, since the brain of <prot>GFAP</prot>-HIV <prot>gp120</prot> mice had increased numbers of <prot>CD3</prot>(+) T cells that were found in close proximity to sites of <prot>CXCL10</prot>/<prot>IP-10</prot> RNA expression.</AbstractText>
