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. 2024 Apr 17;19(4):e0299891.
doi: 10.1371/journal.pone.0299891. eCollection 2024.

Characterization of the brain virome in human immunodeficiency virus infection and substance use disorder

Xin Dang  1 , Barbara A Hanson  1 , Zachary S Orban  1 , Millenia Jimenez  1 , Stephen Suchy  1 , Igor J Koralnik  1
Affiliations

Characterization of the brain virome in human immunodeficiency virus infection and substance use disorder

Xin Dang et al. PLoS One. .

Abstract

Viruses can infect the brain in individuals with and without HIV-infection: however, the brain virome is poorly characterized. Metabolic alterations have been identified which predispose people to substance use disorder (SUD), but whether these could be triggered by viral infection of the brain is unknown. We used a target-enrichment, deep sequencing platform and bioinformatic pipeline named "ViroFind", for the unbiased characterization of DNA and RNA viruses in brain samples obtained from the National Neuro-AIDS Tissue Consortium. We analyzed fresh frozen post-mortem prefrontal cortex from 72 individuals without known viral infection of the brain, including 16 HIV+/SUD+, 20 HIV+/SUD-, 16 HIV-/SUD+, and 20 HIV-/SUD-. The average age was 52.3 y and 62.5% were males. We identified sequences from 26 viruses belonging to 11 viral taxa. These included viruses with and without known pathogenic potential or tropism to the nervous system, with sequence coverage ranging from 0.03 to 99.73% of the viral genomes. In SUD+ people, HIV-infection was associated with a higher total number of viruses, and HIV+/SUD+ compared to HIV-/SUD+ individuals had an increased frequency of Adenovirus (68.8 vs 0%; p<0.001) and Epstein-Barr virus (EBV) (43.8 vs 6.3%; p=0.037) as well as an increase in Torque Teno virus (TTV) burden. Conversely, in HIV+ people, SUD was associated with an increase in frequency of Hepatitis C virus, (25 in HIV+/SUD+ vs 0% in HIV+/SUD-; p=0.031). Finally, HIV+/SUD- compared to HIV-/SUD- individuals had an increased frequency of EBV (50 vs 0%; p<0.001) and an increase in TTV viral burden, but a decreased Adenovirus viral burden. These data demonstrate an unexpectedly high variety in the human brain virome, identifying targets for future research into the impact of these taxa on the central nervous system. ViroFind could become a valuable tool for monitoring viral dynamics in various compartments, monitoring outbreaks, and informing vaccine development.

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Conflict of interest statement

Igor Koralnik receives royalties from UpToDate chapters on CND mass lesions in HIV+ individuals, Progressive Multifocal Leukoencephalopathy and Neurologic Manifestations of COVID-19 the declared competing interest for IJK does not alter our adherence to PLOS ONE policies on sharing data and materials

Figures

Fig 1
Fig 1. ViroFind bioinformatics pipeline analysis of HIV+ and HIV- individuals.
Computed heatmap showing all viral taxa identified by ViroFind in-house pipeline with purple log2 gradient scale indicating the raw number of viral reads. The frequency of each viral species for 36 HIV+ individuals (red) and 36 HIV- individuals (blue) as well as the raw mean read count on a log scale for both groups are shown.
Fig 2
Fig 2. ViroFind bioinformatics pipeline analysis of SUD+ and SUD- individuals.
Computed heatmap showing all viral taxa identified by ViroFind in-house pipeline with purple log2 gradient scale indicating the number of raw viral reads. The frequency of each viral species for 32 SUD+ individuals (red) and 40 SUD- individuals (blue) as well as the raw mean read count on a log scale for both groups are shown.
Fig 3
Fig 3. ViroFind bioinformatics pipeline analysis of HIV+/SUD+ and HIV+/SUD- individuals.
Computed heatmap showing all viral taxa identified by ViroFind in-house pipeline with purple log2 gradient scale indicating the number of raw viral reads. The frequency of each viral type of 16 HIV+/SUD+ individuals (red) and 20 HIV+/SUD- individuals (blue), as well as the raw mean read count on a log scale for both groups are shown.
Fig 4
Fig 4. ViroFind bioinformatics pipeline analysis of HIV-/SUD+ and HIV-/SUD- individuals.
Computed heatmap showing all viral taxa identified by ViroFind in-house pipeline with purple log2 gradient scale indicating the number of raw viral reads. The frequency of each viral species for 16 HIV-/SUD+ individuals (red) and 20 HIV-/SUD- individuals (blue) as well as the raw mean read on a log scale count for each viral species for both groups are shown.
Fig 5
Fig 5. ViroFind bioinformatics pipeline analysis of HIV+/SUD+ and HIV-/SUD+ individuals.
Computed heatmap showing all viral taxa identified by ViroFind in-house pipeline with purple log2 gradient scale. Indicating the raw number of viral reads. The frequency of each viral species for 16 HIV+/SUD+ individuals (red) and 16 HIV-/SUD+ individuals (blue) as well as the raw mean read on a log scale count for each viral species for both groups are shown.
Fig 6
Fig 6. ViroFind bioinformatics pipeline analysis of HIV+/SUD- and HIV-/SUD- individuals.
Computed heatmap showing all viral taxa identified by ViroFind in-house pipeline with purple log2 gradient scale indicating the number of raw viral reads. The frequency of each viral species for 20 HIV+/SUD- individuals (red) and 20 HIV-/SUD- individuals (blue) as well as the raw mean read on a log scale count for each viral species for both groups are shown.
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