Early entry and widespread cellular involvement of HIV-1 DNA in brains of HIV-1 positive asymptomatic individuals.
There is overwhelming evidence that invasion of the central nervous system (CNS) by HIV-1 takes place at an early stage of the infection. It has been demonstrated that HIV-1 DNA is present in brains of asymptomatic individuals. Evidence of immune activation and increased expression of cytokines suggested that neuropathological changes and neuronal and axonal damage could be the effect of the presence of the virus. The purpose of the study is to ascertain whether target cells for HIV-1 in brain of patients at early stage of the infection are the same as those found in AIDS sufferers or if the distribution seen in AIDS patients results from the late spreading of the infection from cells considered traditionally the reservoir of the virus, i.e. microglial cells. Eighteen brains, all HIV-1 DNA positive, as shown by nested polymerase chain reaction (PCR), were selected among the group of HIV-1 positive asymptomatic cases. In 6 of them, HIV-1 DNA was detected by PCR in situ. Positive cells included astrocytes and endothelial cells, in addition to microglial cells. We conclude that astrocytes and endothelial cells are already infected at an early (asymptomatic) stage of the infection and suggest that they might contribute to the damage of the CNS.
An
S F
SF
Department of Neuropathology, Institute of Neurology, University College London, United Kingdom.
Groves
M
M
Gray
F
F
Scaravilli
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology* / Q000821:virology*; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001253:Astrocytes / Q000737:chemistry / Q000821:virology; D001921:Brain / Q000473:pathology* / Q000821:virology*; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis; D004727:Endothelium / Q000821:virology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D017628:Microglia / Q000737:chemistry / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017931:DNA Primers; D004279:DNA, Viral; D005904:Glial Fibrillary Acidic Protein; D016655:HIV Core Protein p24; C067980:CD68 antigen, human; D000097382:CD68 Molecule