Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 07 2019
02 07 2019
Historique:
received:
15
11
2018
accepted:
22
04
2019
entrez:
4
7
2019
pubmed:
4
7
2019
medline:
10
9
2019
Statut:
epublish
Résumé
Elimination of HIV-1 requires clearance and removal of integrated proviral DNA from infected cells and tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 demonstrate viral clearance in latent infectious reservoirs in HIV-1 infected humanized mice. HIV-1 subgenomic DNA fragments, spanning the long terminal repeats and the Gag gene, are excised in vivo, resulting in elimination of integrated proviral DNA; virus is not detected in blood, lymphoid tissue, bone marrow and brain by nested and digital-droplet PCR as well as RNAscope tests. No CRISPR-Cas9 mediated off-target effects are detected. Adoptive transfer of human immunocytes from dual treated, virus-free animals to uninfected humanized mice fails to produce infectious progeny virus. In contrast, HIV-1 is readily detected following sole LASER ART or CRISPR-Cas9 treatment. These data provide proof-of-concept that permanent viral elimination is possible.
Identifiants
pubmed: 31266936
doi: 10.1038/s41467-019-10366-y
pii: 10.1038/s41467-019-10366-y
pmc: PMC6606613
doi:
Substances chimiques
Anti-HIV Agents
0
DNA, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2753Subventions
Organisme : NIDA NIH HHS
ID : P01 DA028555
Pays : United States
Organisme : NIMH NIH HHS
ID : P30 MH062261
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : P30MH092177
Pays : International
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : R01NS036126
Pays : International
Organisme : NIH HHS
ID : R24 OD018546
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH115860
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : R01MH110360
Pays : International
Organisme : NINDS NIH HHS
ID : P01 NS043985
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
ID : P01DA037830
Pays : International
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)
ID : R01DA042706
Pays : International
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : R01NS034239
Pays : International
Organisme : NIMH NIH HHS
ID : P30 MH092177
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG043540
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : P30MH062261
Pays : International
Organisme : NIMH NIH HHS
ID : R01 MH110360
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS034239
Pays : United States
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