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 biologica l features governing HIV entry and tropism in different brain cell types re main unclear, as do the genetics of the virus regulating these events and t he neuropathogenic processes within the brain tissues. HIV-1 was isolated f rom the right and left parietal, occipital, and frontal robes of the brain cortex of three HIV-l-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 r egions showed clear differences on various primary cell types (monocytes, m onocyte-derived macrophages, and T cells), which could discriminate between biological behavior of HIV-1 strains from patients with and without ADC. T he variable effect of different donor cells on tropism was also clearly evi dent. The majority (with a few exceptions) of isolates from different brain regions of all three patients used CCR5 as coreceptor for entry. The consi stent CCR5 use, macrophage tropism, and non-syncytium-inducing phenotype we re the main characteristics of the brain-derived HIV-1 strains from all thr ee 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 patie nts with ADC were more similar to the culture-adapted strains. This suggest s that the emergence of primary cell type-adapted isolates during ADC may p lay a crucial role in the development and progression of the neuropathology associated with ADC. The different genotypes residing in different areas o f brain combined with their differential tropism and coreceptor use suggest that neurotropic variants exist that may be governing the neurological man ifestation of HIV disease in infected patients. (C) 2001 Academic Press.