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

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Dang, Xin, Hanson, Barbara A., Orban, Zachary S., Jimenez, Millenia, Suchy, Stephen, Koralnik, Igor J.·2024·PLOS ONE
DOI 10.1371/journal.pone.0299891PMC PMC11023569
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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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  • These findings, along with reports of a latent brain virome, suggest the brain is not sterile and may harbor various microorganisms.

    “These findings, along with reports of a latent brain virome [136,137], suggest the brain is not sterile and may harbor various microorganisms.”

    From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [137]

    The Results and discussion section, under “Qualitative and quantitative diversity of the brain virome,” reports many viral sequences in prefrontal cortex samples, supporting the reference to a brain virome. Under “Potential role of virus infection of the brain in SUD,” the authors say the viruses *may* remain latent; they do not establish that the detected virome is latent. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Dang, X., Hanson, B. A., Orban, Z. S., Jimenez, M., Suchy, S., & Koralnik, I. J.
Affiliations
Northwestern University (US)
Corresponding author
Koralnik, Igor J.
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2024-04-17
Volume
19
Issue
4
Pages
e0299891
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0299891
PMC
PMC11023569
OpenAlex
W4394874270
Cited by
9
References
1
Citations by year
2026: 3 · 2025: 5 · 2024: 1
FWCI
2.07
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute on Drug Abuse (DP1 DA048493)
  • Manhattan HIV Brain Bank (U24MH100931)
  • Texas NeuroAIDS Research Center (U24MH100930)
  • National Neurological AIDS Bank (U24MH100929)
  • California NeuroAIDS Tissue Network (U24MH100928)
  • Data Coordinating Center (U24MH100925)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
  • Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
Keywords
HIV infection, substance use disorders, viral metagenomics, Epstein-Barr virus, adenovirus, Torque teno virus, hepatitis C virus, viral load, neurovirology
MeSH terms
Virome, Brain, DNA Virus Infections, DNA, Viral, Herpesvirus 4, Human, Female, Humans, Male, Middle Aged, Virus Diseases, HIV Infections, Hepacivirus, Substance-Related Disorders, Epstein-Barr Virus Infections, Torque teno virus

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