Evidence map›Paper›PMID 32525948›Full record

ArticlePLoS pathogens2020

HIV infects astrocytes in vivo and egresses from the brain to the periphery.

Victoria Lutgen, Srinivas D Narasipura, Hannah J Barbian, Maureen Richards, Jennillee Wallace, Roshanak Razmpour, Tetyana Buzhdygan, Servio H Ramirez, Lisa Prevedel, Eliseo A Eugenin and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
13.3field-weighted citation impact, top 1% 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

113 citing papers in PubMed, 144 citations in OpenAlex.

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53 more citing papers are in PubMed but not listed here.

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

11 authors at 3 institutions in 1 country.

Victoria LutgenDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, United States of America.
Srinivas D NarasipuraDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, United States of America.
Hannah J BarbianDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, United States of America.
Maureen RichardsDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, United States of America.
Jennillee WallaceDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, United States of America.
Roshanak RazmpourDepartment of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, United States of America.
Tetyana BuzhdyganDepartment of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, United States of America.
Servio H RamirezDepartment of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, United States of America.
Lisa PrevedelDepartment of Neuroscience, Cell Biology and Anatomy, The University of Texas Medical Branch, Galveston, Texas, United States of America.
Eliseo A EugeninDepartment of Neuroscience, Cell Biology and Anatomy, The University of Texas Medical Branch, Galveston, Texas, United States of America.
Lena Al-HarthiDepartment of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, United States of America.ORCID 0000-0003-3915-3904
Rush University Medical Center · USTemple University · USThe University of Texas Medical Branch at Galveston · US

Funding

TRAINING PROGRAM: DRUGS OF ABUSE RELATED NEUROPEPTIDEST32DA007237 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI ELLEN M UNTERWALD · 1988 to 2026
$10.6M
Astrocyte connexin43 containing channels amplify CNS dysfunction in NeuroAIDSR01MH096625 · NIMH · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI EUGENIN, ELISEO A · 2012 to 2020
$4.5M
Dynamic interaction between HIV in the CNS and peripheral organsR01NS108796 · NINDS · RUSH UNIVERSITY MEDICAL CENTER · PI AL-HARTHI, LENA · 2019 to 2023
$3.7M
Brain endothelial EVs role in the neuropathology of drugs of abuse and HIVR01DA046833 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI POTULA, RAGHAVA, RAMIREZ, SERVIO HEYBERT · 2018 to 2022
$2.6M
HIV latency in astrocytesR01MH100628 · NIMH · RUSH UNIVERSITY MEDICAL CENTER · PI AL-HARTHI, LENA · 2013 to 2017
$2.2M
Mechanisms disrupting astrocyte-neuronal communication in neuroAIDSF32NS089442 · NINDS · RUSH UNIVERSITY MEDICAL CENTER · PI LUTGEN GRONAU, VICTORIA · 2014 to 2016
$177k
NIDA NIH HHS R01 DA046833NIDA NIH HHS T32 DA007237NIMH NIH HHS R01 MH096625NIMH NIH HHS R01 MH100628NINDS NIH HHS F32 NS089442NINDS NIH HHS R01 NS108796
6 · The paper itself

Abstract

HIV invades the brain during acute infection. Yet, it is unknown whether long-lived infected brain cells release productive virus that can egress from the brain to re-seed peripheral organs. This understanding has significant implication for the brain as a reservoir for HIV and most importantly HIV interplay between the brain and peripheral organs. Given the sheer number of astrocytes in the human brain and their controversial role in HIV infection, we evaluated their infection in vivo and whether HIV infected astrocytes can support HIV egress to peripheral organs. We developed two novel models of chimeric human astrocyte/human peripheral blood mononuclear cells: NOD/scid-IL-2Rgc null (NSG) mice (huAstro/HuPBMCs) whereby we transplanted HIV (non-pseudotyped or VSVg-pseudotyped) infected or uninfected primary human fetal astrocytes (NHAs) or an astrocytoma cell line (U138MG) into the brain of neonate or adult NSG mice and reconstituted the animals with human peripheral blood mononuclear cells (PBMCs). We also transplanted uninfected astrocytes into the brain of NSG mice and reconstituted with infected PBMCs to mimic a biological infection course. As expected, the xenotransplanted astrocytes did not escape/migrate out of the brain and the blood brain barrier (BBB) was intact in this model. We demonstrate that astrocytes support HIV infection in vivo and egress to peripheral organs, at least in part, through trafficking of infected CD4+ T cells out of the brain. Astrocyte-derived HIV egress persists, albeit at low levels, under combination antiretroviral therapy (cART). Egressed HIV evolved with a pattern and rate typical of acute peripheral infection. Lastly, analysis of human cortical or hippocampal brain regions of donors under cART revealed that astrocytes harbor between 0.4-5.2% integrated HIV gag DNA and 2-7% are HIV gag mRNA positive. These studies establish a paradigm shift in the dynamic interaction between the brain and peripheral organs which can inform eradication of HIV reservoirs.

Indexed as

AstrocytesBlood-Brain BarrierHippocampusHIV InfectionsVirus ReleaseAnimalsAnti-Retroviral AgentsCell Line, TumorHIV-1HumansMiceMice, Inbred NODMice, KnockoutMice, SCIDAnti-Retroviral Agents

Identifiers

PMID32525948
PMCPMC7289344
OpenAlexW3035632199

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.