Systematic post-mortem analysis of brain tissue from an HIV-1 subtype C viremic decedent revealed a paucity of infection and pathology

Journal of NeuroVirology(2022)

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摘要
Whether the human brain is a robust reservoir for HIV-1 subtype C has yet to be established. We aimed to determine whether HIV-1 subtype C infection can be detected in the brain tissue of a viremic individual at post-mortem and whether the viral burden was differential between different brain regions. This study reports a 38-year-old Zambian female decedent with severe wasting who was on Atripla for antiretroviral therapy. The cause of death was determined to be HIV/AIDS end-stage disease. The QuantStudio 3 Real-Time PCR System analyzed formalin-fixed paraffin-embedded tissue DNA from a systematic sampling of the entire left-brain hemisphere. Plasma and cerebral spinal fluid HIV-1 RNA loads were 576,123 and 14,962 copies/mL, respectively. The lymph node DNA viral load was 2316 copies per 10 6 cells. Two hundred and six (96.3%) tissue blocks had amplifiable DNA. HIV-1 viral DNA was detected in 35.9% of the blocks, the highest in the basal ganglia (66.7%) and the frontal lobe (46%). Overall, HIV detection was random, with low viral copies detected by quantitative polymerase chain reaction (qPCR); the lowest was observed in the occipital (median, IQR, range) 0.0 [0.0–0.0], 0.0–31.3, and the highest in the basal ganglia (mean ± SD , range, 125.1149.5, 0.0–350.0). Significant differences in HIV-1 DNA distribution were observed between the occipital versus parietal ( p = 0.049), occipital versus frontal ( p = 0.019), occipital versus basal ganglia ( p = 0.005), cerebellum versus frontal ( p = 0.021), cerebellum versus basal ganglia ( p = 0.007), and temporal versus frontal ( p = 0.034).
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关键词
HIV-1 subtype C, Brain, Reservoir, Zambia, Post-mortem
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