HIV type 1 viral quasispecies were amplified by polymerase chain reaction (PCR) in the hypervariable V3 region of gp120 from six different regions of the brain (right and left frontal; right and left parietal; and right and left occipital) and from the peripheral blood mononuclear cells (PBMCs) of a patient who died of AIDS dementia complex (ADC). Cloning and sequencing of the entire V3 region suggested the presence of genetically unique sequences in different regions of the brain. In contrast, the blood-derived viral quasispecies carried homogeneous sequences that were characterized by a single octapeptide crest motif (HLGPGSAF), a motif important in viral fusion. The brain-derived viral strains showed extensive sequence heterogeneity and the presence of seven different octapeptide and four different tetrapeptide crest motifs (HIGPGRAF, RIGPGRAF, HIGPGSAI, HLGPGSAF, HIGPESAI, HLGPESAI, and YLRPGSAF). In addition, the brain-derived strains were also characterized by variable net V3 loop charge and hydrophilicity, along with distinct amino acid changes specific to different brain regions. Together, the sequence and phylogenetic analyses are unique in identifying the complexity of a viral quasispecies and its independent regional evolution within the brain compartment. Uniquely divergent viral strains were identified in the frontal regions and their presence was further supported by the presence of multinucleated giant cells (characteristic of HIV encephalopathy) predominantly in the left and right frontal regions. In summary, these analyses suggest that genetically different populations of HIV-1 may be present in different brain compartments and confirm that specific neurotropic variants may exist.

Abstract:AIDS dementia complex (ADC)

The effect of exogenous recombinant interleukin 10 on the replication of low-passage HIV-1 strains in blood-derived monocytes and monocyte-derived-macrophages (MDMs) was examined at various stages of cell maturation after adherence to the plastic substrate. Interleukin 10 inhibited extracellular production of HIV-1 to a greater degree in monocytes infected within 24 hr of adherence than those infected at 5-7 days. Inhibition of viral production as extracellular p24 antigen was most marked when interleukin 10 was preincubated with monocytes for 24-96 hr (optimum, 48 hr), and increased between 2 and 100 ng/ml. Neutralizing antibody to IL-10 reversed the inhibition. Inhibition of HIV production from monocytes and macrophages was maximal at 1 week after a single addition of cytokine, but then HIV production rose to control levels. Interleukin 10 was also found to inhibit reversibly the normal increase in size and maturation of both uninfected and HIV-infected monocytes during 10-15 days of adherence. In addition, cytoplasmic and membrane expression of CD26, a marker of macrophage maturation, was markedly inhibited but the proportion of detaching, apoptotic, or necrotic cells was also not increased. Hence, interleukin 10 reversibly inhibits both monocyte maturation and HIV production from infected monocytes with similar kinetics, suggesting that inhibition of monocyte maturation by IL-10 may have a marked effect of HIV production by these cells.