Short communication: Absence of HIV infection in the choroid plexus of two patients who died rapidly with HIV-associated dementia

Absence of HIV infection of the choroid plexus (CPx) and macrophages in choroidal stroma was observed in two HIV-infected individuals who died 7 weeks and 12 months following the onset of HIV encephalitis. In contrast, the profound macrophage-related pathology associated with HIV infection presented in other neural tissue from 48 brain regions (seven CPx) was analyzed. These data suggest that HIV entry to the CNS may be independent of the CPx. It also emphasizes that the CPx is unlikely to harbor a significant reservoir of HIV in patients who rapidly progress to dementia. © 2008 Mary Ann Liebert, Inc.link_to_subscribed_fulltex

Varied tropism of HIV-1 isolates derived from different regions of adult brain cortex discriminate between patients with and without AIDS dementia complex (ADC): Evidence for neurotropic HIV variants

A number of infected individuals develop neuropathological disorders, such as AIDS dementia complex (ADC), as a consequence of HIV/AIDS. The biological features governing HIV entry and tropism in different brain cell types remain unclear, as do the genetics of the virus regulating these events and the neuropathogenic processes within the brain tissues. HIV-1 was isolated from the right and left parietal, occipital, and frontal lobes of the brain cortex of three HIV-1-infected patients: Two with ADC and one without. The viral strains were studied from the innate tissues and various primary cell cultures. The kinetics and tropism of viral strains from different brain regions showed clear differences on various primary cell types (monocytes, monocyte-derived macrophages, and T cells), which could discriminate between biological behavior of HIV-1 strains from patients with and without ADC. The variable effect of different donor cells on tropism was also clearly evident. The majority (with a few exceptions) of isolates from different brain regions of all three patients used CCR5 as coreceptor for entry. The consistent CCR5 use, macrophage tropism, and non-syncytium-inducing phenotype were the main characteristics of the brain-derived HIV-1 strains from all three patients. Importantly, viral strains derived directly from innate brain tissue of the patient without ADC showed some differences from the cultured variants of the same patient, whereas those from brain tissue of the patients with ADC were more similar to the culture-adapted strains. This suggests that the emergence of primary cell type-adapted isolates during ADC may play a crucial role in the development and progression of the neuropathology associated with ADC. The different genotypes residing in different areas of brain combined with their differential tropism and coreceptor use suggest that neurotropic variants exist that may be governing the neurological manifestation of HIV disease in infected patients. © 2001 Academic Press.link_to_subscribed_fulltex

Unique HIV type 1 V3 region sequences derived from six different regions of brain: Region-specific evolution within host-determined quasispecies

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.link_to_subscribed_fulltex