title: 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.
abstract: 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.
authors.affiliation: Retroviral Genetics Laboratory, Room 3025, Center for Virus Research, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Darcy Road, Westmead, New South Wales, 2145, Australia.
authors.forename: T K
authors.initials: TK
authors.lastname: Smit
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Ng
authors.forename: R
authors.initials: R
authors.lastname: Osborne
authors.forename: B
authors.initials: B
authors.lastname: Brew
authors.forename: N K
authors.initials: NK
authors.lastname: Saksena
mesh_terms: D015526:AIDS Dementia Complex / Q000821:virology*; D000328:Adult; D000595:Amino Acid Sequence; D001921:Brain / Q000473:pathology / Q000821:virology*; D002478:Cells, Cultured; D005260:Female; D016679:Genome, Viral; D015726:Giant Cells; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008264:Macrophages / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000821:virology; D009928:Organ Specificity; D010446:Peptide Fragments / Q000235:genetics; D010802:Phylogeny; D019713:Receptors, CCR5 / Q000378:metabolism; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000821:virology; D018523:Tropism; D014774:Virulence
chemical_list: D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5