Evidence map›Paper›PMID 26727909›Full record

ArticleJournal of neurovirology2016

Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control.

Sarah E Beck, Suzanne E Queen, Raphael Viscidi, Darius Johnson, Stephen J Kent, Robert J Adams, Patrick M Tarwater, Joseph L Mankowski

Abstract read
In one paragraph

Article in Journal of neurovirology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.7field-weighted citation impact, top 29% of its field
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

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Cerebrospinal Fluid CXCL13 as Candidate Biomarker of Intrathecal Immune Activation, IgG Synthesis and Neurocognitive Impairment in People with HIV.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023
    Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Animal models to achieve an HIV cure.Current opinion in HIV and AIDS · 2016
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Sarah E BeckDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, 21205, USA.
Suzanne E QueenDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, 21205, USA.
Raphael ViscidiDepartment of Pediatrics, Johns Hopkins University, Baltimore, MD, 21205, USA.
Darius JohnsonDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, 21205, USA.
Stephen J KentDepartment of Microbiology and Immunology, University of Melbourne, Victoria, 3000, Australia.
Robert J AdamsDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, 21205, USA.
Patrick M TarwaterDivision of Biostatistics and Epidemiology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Joseph L MankowskiDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, 21205, USA. jmankows@jhmi.edu.
Johns Hopkins University · USTexas Tech University · USUniversity of Melbourne · AU

Funding

Project 4: Intracellular mechanism of virus persistence in astrocytes/macrophagesP01MH070306 · NIMH · JOHNS HOPKINS UNIVERSITY · PI CLEMENTS, JANICE E · 2004 to 2015
$16.0M
Training Veterinarians for Careers in Biomedical ResearchT32OD011089 · OD · JOHNS HOPKINS UNIVERSITY · PI JOSEPH L MANKOWSKI · 2012 to 2026
$6.7M
Development of an SPF Macaca nemestrina Breeding ColonyP40OD013117 · OD · JOHNS HOPKINS UNIVERSITY · PI ADAMS, ROBERT J. · 2012 to 2016
$4.9M
Novel SIV Model of HANDR01NS077869 · NINDS · JOHNS HOPKINS UNIVERSITY · PI CLEMENTS, JANICE E, MANKOWSKI, JOSEPH L · 2012 to 2016
$3.8M
Eradicating Latent SIV from the CNS by CCR5 InhibitionR01NS089482 · NINDS · JOHNS HOPKINS UNIVERSITY · PI MANKOWSKI, JOSEPH L · 2014 to 2018
$3.8M
Translational Research in Neuro-AIDS and Mental HealthR25MH080661 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MCARTHUR, JUSTIN CHARLES. · 2007 to 2019
$2.9M
Virus like particles as a therapeutic vaccine for HIVK01OD021323 · OD · JOHNS HOPKINS UNIVERSITY · PI BECK, SARAH · 2016 to 2020
$651k
NIH HHS K01 OD021323NIH HHS P40 OD013117NIH HHS T32 OD011089NIMH NIH HHS P01 MH070306NIMH NIH HHS R25 MH080661NINDS NIH HHS R01 NS077869NINDS NIH HHS R01 NS089482
6 · The paper itself

Abstract

In the fourth decade of the HIV epidemic, the relationship between host immunity and HIV central nervous system (CNS) disease remains incompletely understood. Using a simian immunodeficiency virus (SIV)/macaque model, we examined CNS outcomes in pigtailed macaques expressing the MHC class I allele Mane-A1*084:01 which confers resistance to SIV-induced CNS disease and induces the prototypic viral escape mutation Gag K165R. Insertion of gag K165R into the neurovirulent clone SIV/17E-Fr reduced viral replication in vitro compared to SIV/17E-Fr. We also found lower cerebrospinal fluid (CSF), but not plasma, viral loads in macaques inoculated with SIV/17E-Fr K165R versus those inoculated with wildtype. Although escape mutation K165R was genotypically stable in plasma, it rapidly reverted to wildtype Gag KP9 in both CSF and in microglia cultures. We induced robust Gag KP9-specific CTL tetramer responses by vaccinating Mane-A*084:01-positive pigtailed macaques with a Gag KP9 virus-like particle (VLP) vaccine. Upon SIV/17E-Fr challenge, vaccinated animals had lower SIV RNA in CSF compared to unvaccinated controls, but showed no difference in plasma viral loads. These data clearly demonstrate that viral fitness in the CNS is distinct from the periphery and underscores the necessity of understanding the consequences of viral escape in CNS disease with the advent of new therapeutic vaccination strategies.

Indexed as

AllelesAnimalsCentral Nervous SystemGene ExpressionGene Products, gagHistocompatibility Antigens Class IImmune EvasionMacaca nemestrinaMaleMicrogliaMutationPrimary Cell CultureRNA, ViralSAIDS VaccinesSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusGene Products, gagHistocompatibility Antigens Class IRNA, ViralSAIDS VaccinesVaccines, Virus-Like ParticleCNSEscapeMHC class ISIVViral compartmentalization

Identifiers

PMID26727909
PMCPMC4925266
OpenAlexW2225131642

What OpenQuestion holds

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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 OpenQuestion graph.