Evidence mapPaperPMID 39283947Full record

ArticlePLoS pathogens2024

Microglia and macrophages alterations in the CNS during acute SIV infection: A single-cell analysis in rhesus macaques.

Xiaoke Xu, Meng Niu, Benjamin G Lamberty, Katy Emanuel, Shawn Ramachandran, Andrew J Trease, Mehnaz Tabassum, Jeffrey D Lifson, Howard S Fox

Abstract read
In one paragraph

Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
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  5. Article
  6. Article
  7. Advances in Single-Cell Sequencing for Infectious Diseases: Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  8. Review
  9. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Xiaoke XuDepartment of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Meng NiuDepartment of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Benjamin G LambertyDepartment of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Katy EmanuelDepartment of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Shawn RamachandranDepartment of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Andrew J TreaseDepartment of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Mehnaz TabassumDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Jeffrey D LifsonAIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, Maryland, United States of America.
Howard S FoxDepartment of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.ORCID 0000-0003-2032-374X

Funding

SCRIPPS NEUROAIDS PRECLINICAL STUDIES (SNAPS)P30MH062261 · SCRIPPS RESEARCH INSTITUTE · 2000 to 2005
$10.5M
Uncovering HIV/opioid effects in the brain at the single cell level: transcription, chromatin accessibility, and reservoir analysis in the SIV/cART/morphine/rhesus monkey modelU01DA053624 · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2025 to 2025
$929k
NIDA NIH HHS U01 DA053624NIMH NIH HHS P30 MH062261NIMH NIH HHS R21 MH128057
6 · The paper itself

Abstract

Human Immunodeficiency Virus (HIV) is widely acknowledged for its profound impact on the immune system. Although HIV primarily affects peripheral CD4 T cells, its influence on the central nervous system (CNS) cannot be overlooked. Within the brain, microglia and CNS-associated macrophages (CAMs) serve as the primary targets for HIV and the simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects and establish a viral reservoir. Given the gaps in our understanding of how these cells respond in vivo to acute CNS infection, we conducted single-cell RNA sequencing (scRNA-seq) on myeloid cells from the brains of three rhesus macaques 12 days after SIV infection, along with three uninfected controls. Our analysis revealed six distinct microglial clusters including homeostatic microglia, preactivated microglia, and activated microglia expressing high levels of inflammatory and disease-related molecules. In response to acute SIV infection, the homeostatic and preactivated microglia population decreased, while the activated and disease-related microglia increased. All microglial clusters exhibited upregulation of MHC class I molecules and interferon-related genes, indicating their crucial roles in defending against SIV during the acute phase. All microglia clusters also upregulated genes linked to cellular senescence. Additionally, we identified two distinct CAM populations: CD14lowCD16hi and CD14hiCD16low CAMs. Interestingly, during acute SIV infection, the dominant CAM population changed to one with an inflammatory phenotype. Specific upregulated genes within one microglia and one macrophage cluster were associated with neurodegenerative pathways, suggesting potential links to neurocognitive disorders. This research sheds light on the intricate interactions between viral infection, innate immune responses, and the CNS, providing valuable insights for future investigations.

Indexed as

Macaca mulattaMacrophagesMicrogliaSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusSingle-Cell AnalysisAnimalsBrainCentral Nervous System

Identifiers

PMID39283947
PMCPMC11426456

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.