TY - JOUR
T1 - Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia
AU - Nath, Avi
N1 - Funding Information:
Grant support: NIH. Reprints or correspondence: Dr. A. Nath, Dept. of Neurology, Johns Hopkins University, 600 N. Wolfe St., Meyer 6-109, Baltimore, MD 21287-7609 (anath1@jhmi.edu).
PY - 2002/12/1
Y1 - 2002/12/1
N2 - Human immunodeficiency virus (HIV) infection of the nervous system is unique when compared with other viral encephalitides. Neuronal cell loss occurs in the absence of neuronal infection. Viral proteins, termed "virotoxins," are released from the infected glial cells that initiate a cascade of positive feedback loops by activating uninfected microglial cells and astrocytes. These activated cells release a variety of toxic substances that result in neuronal dysfunction and cell loss. The virotoxins act by a hit and run phenomenon. Thus, a transient exposure to the proteins initiates the neurotoxic cascade. High concentrations of these proteins likely occur in tight extracellular spaces where they may cause direct neurotoxicity as well. The emerging concepts in viral protein-induced neurotoxicity are reviewed as are the neurotoxic potential of each protein. Future therapeutic strategies must target common mechanisms such as oxidative stress and dysregulation of intracellular calcium involved in virotoxin-mediated neurotoxicity.
AB - Human immunodeficiency virus (HIV) infection of the nervous system is unique when compared with other viral encephalitides. Neuronal cell loss occurs in the absence of neuronal infection. Viral proteins, termed "virotoxins," are released from the infected glial cells that initiate a cascade of positive feedback loops by activating uninfected microglial cells and astrocytes. These activated cells release a variety of toxic substances that result in neuronal dysfunction and cell loss. The virotoxins act by a hit and run phenomenon. Thus, a transient exposure to the proteins initiates the neurotoxic cascade. High concentrations of these proteins likely occur in tight extracellular spaces where they may cause direct neurotoxicity as well. The emerging concepts in viral protein-induced neurotoxicity are reviewed as are the neurotoxic potential of each protein. Future therapeutic strategies must target common mechanisms such as oxidative stress and dysregulation of intracellular calcium involved in virotoxin-mediated neurotoxicity.
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U2 - 10.1086/344528
DO - 10.1086/344528
M3 - Article
C2 - 12424697
AN - SCOPUS:0036891081
VL - 186
SP - S193-S198
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - SUPPL. 2
ER -