Effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques.

Animals Macaca mulatta / genetics Leukocytes, Mononuclear Post-Exposure Prophylaxis Measles / drug therapy Measles virus / genetics RNA, Viral

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
20 04 2023
Historique:
received: 05 12 2022
accepted: 14 04 2023
medline: 24 4 2023
pubmed: 21 4 2023
entrez: 20 04 2023
Statut: epublish

Résumé

Measles is a systemic disease initiated in the respiratory tract with widespread measles virus (MeV) infection of lymphoid tissue. Mortality can be substantial, but no licensed antiviral therapy is available. We evaluated both post-exposure prophylaxis and treatment with remdesivir, a broad-spectrum antiviral, using a well-characterized rhesus macaque model of measles. Animals were treated with intravenous remdesivir for 12 days beginning either 3 days after intratracheal infection (post-exposure prophylaxis, PEP) or 11 days after infection at the onset of disease (late treatment, LT). As PEP, remdesivir lowered levels of viral RNA in peripheral blood mononuclear cells, but RNA rebounded at the end of the treatment period and infectious virus was continuously recoverable. MeV RNA was cleared more rapidly from lymphoid tissue, was variably detected in the respiratory tract, and not detected in urine. PEP did not improve clinical disease nor lymphopenia and reduced the antibody response to infection. In contrast, LT had little effect on levels of viral RNA or the antibody response but also did not decrease clinical disease. Therefore, remdesivir transiently suppressed expression of viral RNA and limited dissemination when provided as PEP, but virus was not cleared and resumed replication without improvement in the clinical disease parameters evaluated.

Identifiants

DOI: 10.1038/s41598-023-33572-7 PMID: 37081035 PMC: PMC10116456
pubmed: 37081035
doi: 10.1038/s41598-023-33572-7
pii: 10.1038/s41598-023-33572-7
pmc: PMC10116456
doi:

Substances chimiques

remdesivir 3QKI37EEHE
RNA, 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

6463

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI153140
Pays : United States
Organisme : NIH HHS
ID : T32 OD011089
Pays : United States
Organisme : NIH HHS
ID : T32 AI052071
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Nadine A Peart Akindele (NA)

Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA.
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Rm E5636, Baltimore, MD, 21205, USA.
United States Food and Drug Administration, Silver Spring, MD, 20993, USA.

Laharika Dasharath Katamoni (LD)

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Rm E5636, Baltimore, MD, 21205, USA.
Zanvyl Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, 21205, USA.
BioCheck, Inc., South San Francisco, CA, 94080, USA.

Jacqueline Brockhurst (J)

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Rm E5636, Baltimore, MD, 21205, USA.
Department of Molecular and Comparative Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA.

Shristi Ghimire (S)

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Rm E5636, Baltimore, MD, 21205, USA.

San Suwanmanee (S)

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Rm E5636, Baltimore, MD, 21205, USA.
Department of Epidemiology, Faculty of Public Health, Mahidol University, Bangkok, Thailand.

Lisa Pieterse (L)

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Rm E5636, Baltimore, MD, 21205, USA.

Kelly A Metcalf Pate (KA)

Department of Molecular and Comparative Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA.
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Elaine Bunyan (E)

Gilead Sciences Inc., Foster City, CA, 94404, USA.

Roy Bannister (R)

Gilead Sciences Inc., Foster City, CA, 94404, USA.

Tomas Cihlar (T)

Gilead Sciences Inc., Foster City, CA, 94404, USA.

Danielle P Porter (DP)

Gilead Sciences Inc., Foster City, CA, 94404, USA.

Diane E Griffin (DE)

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Rm E5636, Baltimore, MD, 21205, USA. dgriffi6@jhu.edu.

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Recherchemedicale.com › Eucaryotes › Animaux › Effect of remdesivir post-exposure prophylaxis...
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