TY - JOUR
T1 - An experimental model system for HIV-1-induced brain injury
AU - Gendelman, Howard E.
AU - Genis, Peter
AU - Jett, Marti
AU - Zhai, Qi hui
AU - Nottet, Hans S.L.M.
N1 - Funding Information:
We wish to thank Karen Spiegel for outstanding administrative support. These works were funded in part by AmFAR grant 02065-15-RGR H.E.G., and the University of Nebraska Research Initiative start up funds, NIH grants PO1 NS31492-01 (H.E.G.), and PO1 HL43628-05 (H.E.G.). Dr Howard Gendelman is a Carter Wallace Fellow of the Department of Pathology and Microbiology of the University of Nebraska Medical Center; Dr Hans Nottet is a Nicholas B. Badami Scholar of the Laboratory of Viral Pathogenesis, Department of Pathology and Microbiology, University of Nebraska Medical Center.
PY - 1994
Y1 - 1994
N2 - The pathological hallmark of HIV infection in brain is productive viral replication in cells of mononuclear phagocyte lineage including brain macrophages, microglia and multinucleated giant cells (Koenig et al., 1986; Wiley et al., 1986; Gabuzda et al., 1986; Stoler et al., 1986). These cells secrete viral and cell encoded neurotoxins that lead to neuronal injury, glial proliferation and myelin pallor during advancing disease (Genis et al., 1992; Giulian et al., 1990, 1993; Pulliam et al., 1991). The apparent paradox between the distribution and numbers of virus infected cells and brain tissue pathology support indirect mechanisms for CNS damage (Epstein, 1993; Geleziunas et al., 1992; Merrill and Chen, 1992; Michaels et al., 1988; Price et al., 1988). First, brain macrophages and microglia can produce neurotoxins by secretion of viral proteins (for example, gp120) (Dawson et al., 1991; Merrill et al., 1989; Lipton et al., 1990; Lipton, 1993). Second, HIV primes macrophages for immune activation to produce neurotoxins including: cytokines (TNF(α and IL-1β), eicosanoids, quinolinate and nitric oxide (NO). Chronic immune stimulation mediated by opportunistic infections and chronic interferon gamma (IFNγ) production (in and outside the CNS) continues the process of macrophage activation leading to progressive neural injury. The hyperresponsiveness of HIV-infected macrophages to activation results in production of cellular factors that activate uninfected macrophages. This suggests that HIV-infected macrophages are both perpetrators and amplifiers for neurotoxic activities.
AB - The pathological hallmark of HIV infection in brain is productive viral replication in cells of mononuclear phagocyte lineage including brain macrophages, microglia and multinucleated giant cells (Koenig et al., 1986; Wiley et al., 1986; Gabuzda et al., 1986; Stoler et al., 1986). These cells secrete viral and cell encoded neurotoxins that lead to neuronal injury, glial proliferation and myelin pallor during advancing disease (Genis et al., 1992; Giulian et al., 1990, 1993; Pulliam et al., 1991). The apparent paradox between the distribution and numbers of virus infected cells and brain tissue pathology support indirect mechanisms for CNS damage (Epstein, 1993; Geleziunas et al., 1992; Merrill and Chen, 1992; Michaels et al., 1988; Price et al., 1988). First, brain macrophages and microglia can produce neurotoxins by secretion of viral proteins (for example, gp120) (Dawson et al., 1991; Merrill et al., 1989; Lipton et al., 1990; Lipton, 1993). Second, HIV primes macrophages for immune activation to produce neurotoxins including: cytokines (TNF(α and IL-1β), eicosanoids, quinolinate and nitric oxide (NO). Chronic immune stimulation mediated by opportunistic infections and chronic interferon gamma (IFNγ) production (in and outside the CNS) continues the process of macrophage activation leading to progressive neural injury. The hyperresponsiveness of HIV-infected macrophages to activation results in production of cellular factors that activate uninfected macrophages. This suggests that HIV-infected macrophages are both perpetrators and amplifiers for neurotoxic activities.
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U2 - 10.1016/S0960-5428(06)80256-1
DO - 10.1016/S0960-5428(06)80256-1
M3 - Article
C2 - 7874386
AN - SCOPUS:0027970289
SN - 0960-5428
VL - 4
SP - 189
EP - 193
JO - Advances in Neuroimmunology
JF - Advances in Neuroimmunology
IS - 3
ER -