IN-SITU DETECTION OF POLYMERASE CHAIN REACTION-AMPLIFIED HIV-1 NUCLEIC-ACIDS AND TUMOR-NECROSIS-FACTOR-ALPHA RNA IN THE CENTRAL-NERVOUS-SYSTEM

This study determined the distribution of in situ polymerase chain rea ction (PCR)-amplified HIV-1 nucleic acids in the central nervous syste m (CNS). Amplified viral DNA was detected in each of the seven HIV-1-p ositive cases and in none of the seven negative controls. HIV-1 DNA wa s rarely detected with standard in situ hybridization, consistent with low levels of proviral DNA. Inpatients with minimal clinical and path ological CNS involvement, only rare HIV-1 DNA-positive perivascular mi croglial cells were noted. In patients with dementia, many infected ne urons and astrocytes as well as microglial cells were detected. Severe disease was also characterized by the detection of tumor necrosis fac tor-alpha (TNF-alpha) mRNA and viral RNA by reverse transcription (RT) in situ PCR These results suggest that HIV-1 commonly exists in the C NS in the asymptomatic patient and that progression is marked by a dra matic increase of the number of cells with HIV-1 DNA, including neuron s and astrocytes, and a concomitant upregulation of both viral and TNF -alpha transcription