Evidence map›Paper›PMID 42555626›Full record

ArticlePLoS pathogens2026

Long-term depletion of KIR3DL01+ NK cells by adeno-associated viral-vectored antibody delivery alters chronic SIV infection.

Kjell Sandstrom, Grace N Hagedorn, Sean C Robinson, Julia E Katz, Trent M Prall, Roger W Wiseman, Jun Xie, Matthew R Gardner, Andrea M Weiler, Grace A VanSleet and 11 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Kjell SandstromDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Grace N HagedornDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Sean C RobinsonDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Julia E KatzDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Trent M PrallDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Roger W WisemanDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Jun XieDepartment of Genetics and Cellular Medicine, Horae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America.
Matthew R GardnerDepartment of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GeorgiaUnited States of America.
Andrea M WeilerWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Grace A VanSleetWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Sydney M StroscheinWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
José L Sanchez HernandezWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Amy W MoyWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Jeffrey D LifsonAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
Saverio V Capuano IiiWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Alessandro PoggiMolecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Guangping GaoDepartment of Genetics and Cellular Medicine, Horae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America.
David H O'ConnorDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Thomas C FriedrichWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Vadim A KlenchinDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
David T EvansDepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.ORCID 0000-0003-2498-6292

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
WNPRC Supplemental Request for Nonhuman Primate Enclosures to Equip HIV/AIDS-Related Research FacilitiesP51OD011106 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI Dorota A. Grejner-Brzezinska · 2012 to 2026
$150.7M
cGMP Manufacture, Fill-Finish, Release, Analytical and Stability Testing and Stability Program of a Nanoparticle Based HIV Envelope Vaccine75N93022D00005 · NIAID · INTERNATIONAL AIDS VACCINE INITIATIVE · PI HASSELL, THOMAS · 2022 to 2025
$8.0M
KIR and MHC Class I Immunogenetics in SIV InfectionR37AI095098 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI David T Evans · 2019 to 2026
$5.6M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00005 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL E · 2020 to 2025
$5.1M
Evaluation of didehydro-Cortistatin A as a block-and-lock agent for a functional HIV cure in a macaque modelR01AI167732 · NIAID · UNIVERSITY OF FLORIDA · PI David T Evans, Susana T Valente · 2021 to 2026
$4.3M
Assessing ADCC and Fc-mediated Protection against HIVR01AI148379 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI EVANS, DAVID T, FINZI, ANDRES · 2019 to 2023
$3.8M
Harnessing adaptive NK cell transfer to deplete viral reservoirsR01AI161816 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI BARKER, EDWARD, EVANS, DAVID T · 2021 to 2025
$3.8M
Tethering lentiviral restriction to Fc-mediated antibody responsesR01AI155163 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI EVANS, DAVID T · 2020 to 2024
$3.2M
KIR and MHC Class I Immunogenetics in SIV InfectionR01AI095098 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI EVANS, DAVID T · 2012 to 2016
$2.7M
NHLBI NIH HHS 75N92020D00005NIAID NIH HHS 75N93022D00005NIAID NIH HHS R01 AI095098NIAID NIH HHS R01 AI148379NIAID NIH HHS R01 AI155163NIAID NIH HHS R01 AI161816NIAID NIH HHS R01 AI167732NIAID NIH HHS R37 AI095098NIDA NIH HHS 75N95020D00005NIH HHS 75N91019D00024NIH HHS 75N93023D00005NIH HHS 75N99020D00005NIH HHS P51 OD011106
6 · The paper itself

Abstract

Natural killer (NK) cells are key innate effectors during antiviral immune responses, with their activity regulated in part by interactions between polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their major histocompatibility complex class I (MHC I) ligands on target cells. In human immunodeficiency virus (HIV) infection, certain KIR and MHC I allelic combinations are associated with enhanced viral control and delayed disease progression. To interrogate the contribution of a common KIR+ NK cell subset to the immune response to simian immunodeficiency virus (SIV) infection of rhesus macaques, we depleted KIR3DL01+ cells using an adeno-associated virus (AAV) vector encoding a KIR3DL01-reactive monoclonal antibody. AAV delivery resulted in high and durable antibody expression with minimal anti-drug antibody responses, leading to sustained depletion of KIR3DL01+ NK cells from blood, lymph nodes, and gut-associated lymphoid tissue for more than nine months. Following intrarectal SIV challenge, there was no difference in peak viremia between the two groups. However, KIR3DL01-depleted animals exhibited a modest increase in chronic viremia, reaching statistical significance at multiple timepoints relative to KIR3DL01+ controls. Phenotypic analysis revealed ongoing NK cell maturation in peripheral blood and lymphoid tissue, accompanied by increased expression of activation and proliferation markers during acute and early chronic infection. An expansion of NKG2D+ NK cells was also observed in chronic SIV infection. These findings suggest that KIR3DL01+ NK cells contribute to the inhibition of SIV replication during chronic infection. Moreover, they demonstrate the feasibility of AAV-vectored antibody delivery for long-term, perhaps indefinite depletion of a lymphocyte subset in a nonhuman primate model.

Indexed as

Antibodies, MonoclonalAntibodies, ViralKiller Cells, NaturalReceptors, KIR3DL1Simian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusAnimalsChronic DiseaseDependovirusGenetic VectorsLymphocyte DepletionMacaca mulattaAntibodies, MonoclonalAntibodies, ViralReceptors, KIR3DL1

Identifiers

PMID42555626
PMCPMC13456248

What Socratic holds

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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 Socratic graph.