Enhanced Expression of Proinflammatory Cytokines in the Central Nervous System Is Associated with Neuroinvasion by Simian Immunodeficiency Virus and the Development of Encephalitis

New England Regional Primate Research Center, Southborough, Massachusetts 01772-9102, USA.
Journal of Virology (Impact Factor: 4.44). 07/2002; 76(11):5797-802. DOI: 10.1128/JVI.76.11.5797-5802.2002
Source: PubMed


Inflammatory cytokines are believed to play an important role in the pathogenesis of human immunodeficiency virus type 1-associated encephalitis. To examine this in the simian immunodeficiency virus (SIV)-infected macaque model of neuroAIDS, inflammatory cytokine gene expression was evaluated in the brains of macaques infected with pathogenic SIV(mac251) by reverse transcriptase PCR. Interleukin-1 beta was readily detected in the brains of all animals evaluated, regardless of infection status or duration of infection. Tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) transcripts were undetectable in the brains of uninfected control animals but were upregulated at 7 and 14 days postinoculation. At the terminal stage of infection, TNF-alpha and IFN-gamma transcripts were coexpressed in the brains of four of five animals with SIV encephalitis (SIVE). Within an encephalitic brain, TNF-alpha and IFN-gamma transcripts were detected in six of seven regions with histologic evidence of SIVE, suggesting a direct relationship between neuropathology and altered cytokine gene expression. With combined fluorescent in situ hybridization and immunofluorescence, TNF-alpha-expressing cells were frequently identified as CD68-positive macrophages within perivascular lesions. These observations provide evidence that cytokines produced by activated inflammatory macrophages are an important element in the pathogenesis of SIVE.


Available from: Andrew A Lackner
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    • "Human immunodeficiency virus (HIV) gains access to the central nervous system (CNS) soon after the systematic infection (Roberts et al. 2004; Orandle et al. 2002) and causes a variety of neurological dysfunctions, collectively called HIVassociated neurocognitive disorder (HAND) (Kramer- Hammerle et al. 2005; Navia et al. 1986). Despite the success of combination antiretroviral therapy (cART) in suppressing HIV replication in the peripheral blood, improving immune function and prolonging the lifespan of HIV-infected individuals (Cysique et al. 2004; Sacktor et al. 2002), HAND has remained prevalent (Sacktor et al. 2002; Langford et al. 2003; Kandanearatchi et al. 2003). "
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    • "Isolation of SIV sequence variants from SIVmac251-infected rhesus macaques SIV gp120 sequence variants were cloned and sequenced from archived samples stored at À 80 1C, available from previous studies of SIVmac251-infected rhesus macaques (Orandle et al., 2002; Williams et al., 2002, 2001) (Table 1). Four macaques (Group I) were infected with SIVmac251 stock from the Desrosiers lab; two were inoculated intravenously and two intravaginally. "
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    • "To study the effects of downstream activation on astrocytes subsequent to stellation, we stimulated stellated astrocytes with TNF-α as described in Figure 1. This proinflammatory cytokine has been observed in viral encephalitides (Orandle et al., 2002), bacterial infection (Phulwani et al., 2008), and stroke (Tuttolomondo et al., 2012). By treating with TNF-α with and without transient acidification we are able to model a broad-spectrum of disease states. "
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