Year: 2019
Type: article
Abstract: Background: HIV-1 can be detected in the CNS at all stages of infection; however, the timing of infection and evolutionary pathways have not been well-delineated.Here, we investigated the genetic patterns of the virus from CNS and lymphoid tissues from 7 patients with and without Neuro-AIDS.Methods: DNA was extracted from 12 post-mortem tissues (frontal lobe, cerebellum and spleen) and HIV-1 env genes were sequenced using PacBio SMRT technology.Sequences were filtered for quality and aligned using MAFFT and AliView, resulting in 'Optimized Alignments' (range 12,650 -44,368 sequences/tissue).The number of glycosylation sites, length, charge and predicted co-receptor usage were evaluated for env variable regions (V1-V5).For each tissue, high-quality consensus sequence (HQCS) alignments were produced by removing the variable regions and grouping sequences with 99% genetic similarity.HQCS10 alignments were then generated by including only variants that represented >10 reads.HQCS10 sequences from all patients/tissues were combined, and used to infer a maximum likelihood ML tree.Genetic clusters were identified using a hierarchical strategy based on genetic distance thresholds at 1%-5%.Results: Patients were distinctly separated into clades on the HQCS10 ML tree, and in each patient with multiple tissues, brain sequences formed a distinct and separate clade with respect to spleen sequences.Branch lengths were highly variable among patients.To quantify variation and structure among patients' tissues, sequences were clustered using a range of genetic distance thresholds.At the lowest threshold (1%), tissue sequences from all but one patient were separated into distinct clusters.As genetic distance increased, the number of clusters per patient decreased and tissue sequences merged together.A patient without Neuro-AIDS showed the highest diversity between brain and spleen.Variable region analysis of the Optimized Alignments showed similar variability within and among patients.Taken together, these patterns are consistent with continued viral evolution in the brain reservoir.Conclusions: While minor correlations were found between genetic diversity, disease, length of infection and drug use, it was clear that brain and spleen tissues are compartmentalized in patients with long-term infection, with and without neuro-AIDS.PP 3.17
Source: Journal of Virus Eradication
Institution: University of Pennsylvania
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
OpenAlex ID: W3041742723