Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia.
OBJECTIVE
To relate the expression of HIV regulatory proteins and HIV-specific mRNA in the brain cells of infected individuals with clinical neurological disease.


METHODS
Formalin-fixed postmortem brain tissue from 14 HIV-infected adult patients, with previous repeated neurological and neuroradiological examinations, was studied by immunohistochemical and molecular biological methods. Samples from non-infected brains served as controls.


METHODS
Immunohistochemistry with monoclonal antibodies (MAb) was combined with in situ RNA hybridization. Target cells were identified with MAb to glial fibrillary acidic protein (GFAP; astrocytes), CD68 (activated macrophages) and Ricinus communis agglutinin (RCA-1; microglia, endothelial cells). For HIV, a panel of MAb against HIV Nef, Tat, Rev and Env proteins or probes specific for all classes of mRNA (nef), for singly or non-spliced mRNA (env) and for non-spliced mRNA (gag/pol) were used.


RESULTS
Nef protein was detected in subcortical or subpial astrocytes in seven out of 14 samples, and in multinucleated giant cells in two cases. Gag/pol or env mRNA-expressing astrocytes were detected in four cases. In four out of five cases studied, HIV Rev, but not Tat, was also expressed in astrocytes. Six out of the seven patients with Nef-positive astrocytes had suffered from moderate to severe dementia. The patient with most rapidly progressing severe dementia showed extensive HIV mRNA expression together with Nef and Rev expression in astrocytes.


CONCLUSIONS
In adult human brain, astrocytes are infected by HIV and preferentially express HIV Nef and Rev proteins but are also sometimes productively infected. Astrocyte infection is associated with moderate to severe dementia which agrees with recent knowledge on the housekeeping activities of astrocytes and their eventual role in learning and memory.
Department of Dermatology and Venereal Diseases, University of Helsinki, Finland.
A
A
Ranki
M
M
Nyberg
V
V
Ovod
M
M
Haltia
I
I
Elovaara
R
R
Raininko
H
H
Haapasalo
K
K
Krohn
D015526:AIDS Dementia Complex / Q000473:pathology / Q000821:virology*; D000328:Adult; D001253:Astrocytes / Q000473:pathology / Q000821:virology*; D001921:Brain / Q000473:pathology / Q000821:virology*; D005260:Female; D015967:Gene Expression Regulation, Viral; D015693:Gene Products, nef / Q000235:genetics*; D015694:Gene Products, rev / Q000235:genetics*; D006678:HIV / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D015694:Gene Products, rev; D012333:RNA, Messenger; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus