دورية أكاديمية
أعرض في EDS

Smallpox lesion characterization in placebo-treated and tecovirimat-treated macaques using traditional and novel methods.

التفاصيل البيبلوغرافية
العنوان: Smallpox lesion characterization in placebo-treated and tecovirimat-treated macaques using traditional and novel methods.
المؤلفون: Bell TM; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America., Facemire P; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America., Bearss JJ; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America., Raymond JL; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America., Chapman J; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America., Zeng X; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America., Shamblin JD; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America., Williams JA; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America., Grosenbach DW; SIGA Technologies, Inc., Corvallis, Oregon, United States of America., Hruby DE; SIGA Technologies, Inc., Corvallis, Oregon, United States of America., Damon IK; Poxvirus and Rabies Branch, Centers for Disease Control and Prevention (CDC) Atlanta, Georgia, United States of America., Goff AJ; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America., Mucker EM; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
المصدر: PLoS pathogens [PLoS Pathog] 2024 Feb 22; Vol. 20 (2), pp. e1012007. Date of Electronic Publication: 2024 Feb 22 (Print Publication: 2024).
نوع المنشور: Clinical Trial, Veterinary; Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: Dermatitis* , Smallpox*/drug therapy , Smallpox*/pathology , Variola virus*, Animals ; Benzamides ; Isoindoles ; Macaca fascicularis ; United States
مستخلص: Smallpox was the most rampant infectious disease killer of the 20th century, yet much remains unknown about the pathogenesis of the variola virus. Using archived tissue from a study conducted at the Centers for Disease Control and Prevention we characterized pathology in 18 cynomolgus macaques intravenously infected with the Harper strain of variola virus. Six macaques were placebo-treated controls, six were tecovirimat-treated beginning at 2 days post-infection, and six were tecovirimat-treated beginning at 4 days post-infection. All macaques were treated daily until day 17. Archived tissues were interrogated using immunohistochemistry, in situ hybridization, immunofluorescence, and electron microscopy. Gross lesions in three placebo-treated animals that succumbed to infection primarily consisted of cutaneous vesicles, pustules, or crusts with lymphadenopathy. The only gross lesions noted at the conclusion of the study in the three surviving placebo-treated and the Day 4 treated animals consisted of resolving cutaneous pox lesions. No gross lesions attributable to poxviral infection were present in the Day 2 treated macaques. Histologic lesions in three placebo-treated macaques that succumbed to infection consisted of proliferative and necrotizing dermatitis with intracytoplasmic inclusion bodies and lymphoid depletion. The only notable histologic lesion in the Day 4 treated macaques was resolving dermatitis; no notable lesions were seen in the Day 2 treated macaques. Variola virus was detected in all three placebo-treated animals that succumbed to infection prior to the study's conclusion by all utilized methods (IHC, ISH, IFA, EM). None of the three placebo-treated animals that survived to the end of the study nor the animals in the two tecovirimat treatment groups showed evidence of variola virus by these methods. Our findings further characterize variola lesions in the macaque model and describe new molecular methods for variola detection.
Competing Interests: DWG and DEH are employed by SIGA Technologies. SIGA Technologies holds commercial interest in tecovirimat and provided tecovirimat for the study referenced. Other authors have no conflict of interest.
(Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
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المشرفين على المادة: 0 (Benzamides)
0 (Isoindoles)
تواريخ الأحداث: Date Created: 20240222 Date Completed: 20240226 Latest Revision: 20240325
رمز التحديث: 20240325
مُعرف محوري في PubMed: PMC10883539
DOI: 10.1371/journal.ppat.1012007
PMID: 38386661
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1012007