Encephalopathy in AIDS--increased formation of beta-chemokines in monocytes after HIV-1 virus infection: mechanisms of CNS involvement
Article
Mayer, V, Schmidtmayerová, H. (1997). Encephalopathy in AIDS--increased formation of beta-chemokines in monocytes after HIV-1 virus infection: mechanisms of CNS involvement
. 98(6), 330-334.
Mayer, V, Schmidtmayerová, H. (1997). Encephalopathy in AIDS--increased formation of beta-chemokines in monocytes after HIV-1 virus infection: mechanisms of CNS involvement
. 98(6), 330-334.
The characteristic trait of the family of lentiviruses (Retroviridae) which includes the human immune deficiency virus (HIV), is the tendency to cause a subacute neurologic disease in their animal host. The neuraxis can be inflicted at all its levels. In the advanced stage of HIV disease, more than 60 percent of patients suffer from a clinically evident neurological dysfunction. Neuropathologic changes are demonstrated in 75 - 90 percent of them at autopsy. HIV enters the CNS during the early phase of infection. HIV replicates predominantly in the nervous tissue macrophages which serve also as intrathecal reservoirs of infection. HIV isolated from the CNS is usually macrophagotropic. Neural cells are not susceptible to a productive HIV infection, contrasting with the permissivity of activated astroglial cells. The neuropathological picture of the brain involvement is typical by the giant multinuclear cells, i.e. fused monocytes/macrophages, then neuronal loss and changes in the white matter. The clinical manifestations of CNS involvement (AIDS encephalopathy) in HIV disease are variable protean, frequently associated with dementia. The pathogenesis of the neurological disease remains elusive. The cells supporting the HIV replication in the CNS (microglia, monocytes, astroglia) do not play a major role in dementia development. The neurotoxicity of viral glycoproteins, virus-induced cytokines and neurotoxin produced by CNS macrophages infected with particularly efficiently replicating HIV strains are being intensively studied. Dementia is associated with an increased virus load in the brain in the advanced stage of HIV disease. Neurotoxicity associated with HIV-infected microglial cells and macrophages activity remain to be considered, for the time being, as the most likely pathogenetic mechanism of neural dysfunction and injury. Our investigations have demonstrated that HIV infection of macrophages stimulate considerably the synthesis of MIP-1-alpha, MIP-1-beta RANTES chemokines (subgroup CC). These substances by their chemoattractant and activating properties may participate in the pathogenesis of HIV/AIDS encephalopathy, contributing to leukocytosis and inflammation, increasing thus the population of HIV-susceptible cells, facilitating their infection and enhancing finally the intrathecal spread of virus. (Tab. 2, Ref. 22.)
