Related Experiment Videos
Expression of HIV regulatory and structural mRNA in the central nervous system
C A Wiley1, M Baldwin, C L Achim
1Neuropathology Division, Presbyterian University Hospital, Pittsburgh, Pennsylvania 15213-2582, USA.
Objective:
HIV encephalitis is observed in approximately one-half of AIDS autopsies. Although most investigators would agree that central nervous system (CNS) macrophages are the predominant infected cell in HIV encephalitis, there remains some controversy regarding whether other CNS cells can be infected by HIV and thus show the molecular characteristics of such an infection.
Design And Methods:
Using reverse transcriptase polymerase chain reaction (PCR) and immunocytochemistry (ICC), we examined CNS tissues from AIDS and control autopsies for the presence of non-productive HIV infection.
Results:
Single-spliced mRNA for structural envelope proteins were detected in the basal ganglia of only one of nine HIV-seropositive autopsies without HIV encephalitis and none of five seronegative autopsy controls. Double-spliced mRNA for regulatory proteins (e.g., Nef and Tat) were not detected in either the seropositive non-HIV encephalitis or seronegative controls. Both single and double-spliced viral RNA could be detected in basal ganglia of 10 out of 13 autopsies with HIV encephalitis. Similar findings were obtained when cerebral white matter was examined. Using PCR primers that distinguish single from double-spliced mRNA, we found no evidence for selective expression of the Nef regulatory gene.
Conclusions:
These data suggest that expression of HIV mRNA in the CNS is limited to those patients with HIV encephalitis. Further HIV encephalitis appears to be a chronic permissive infection of the CNS, without evidence of restricted Nef transcript expression.
Insights
Central nervous system (CNS) macrophages are primarily infected in HIV encephalitis. This study found HIV mRNA expression in the CNS is limited to patients with HIV encephalitis, indicating a chronic permissive infection.
Area of Science:
- Neurovirology
- Immunology
- Pathology
Background:
- HIV encephalitis affects approximately 50% of AIDS autopsies.
- While CNS macrophages are considered the primary infected cells, the role of other CNS cells remains debated.
Purpose of the Study:
- To investigate the presence and molecular characteristics of non-productive HIV infection in central nervous system (CNS) cells.
- To determine if HIV infects cells beyond macrophages in the CNS.
Main Methods:
- Utilized reverse transcriptase polymerase chain reaction (PCR) and immunocytochemistry (ICC).
- Examined CNS tissues from both AIDS and control autopsies.
Main Results:
- Single-spliced HIV mRNA for structural proteins was detected in basal ganglia of one HIV-seropositive case without encephalitis, but not in controls.
- Both single and double-spliced viral RNA were found in the basal ganglia of 10/13 autopsies with HIV encephalitis.
- Similar findings were observed in cerebral white matter, with no selective expression of the Nef gene.
Conclusions:
- HIV mRNA expression in the CNS is predominantly associated with HIV encephalitis.
- HIV encephalitis appears to be a chronic, permissive infection within the CNS.
- No evidence of restricted Nef transcript expression was found in infected CNS tissues.