In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2021-9-21), p. e1009633-
Abstract:
Smallpox, caused by the solely human pathogen Variola virus (VARV), was declared eradicated in 1980. While known VARV stocks are secure, smallpox remains a bioterrorist threat agent. Recent U.S. Food and Drug Administration approval of the first smallpox anti-viral (tecovirimat) therapeutic was a successful step forward in smallpox preparedness; however, orthopoxviruses can become resistant to treatment, suggesting a multi-therapeutic approach is necessary. Animal models are required for testing medical countermeasures (MCMs) and ideally MCMs are tested directly against the pathogen of interest. Since VARV only infects humans, a representative animal model for testing therapeutics directly against VARV remains a challenge. Here we show that three different humanized mice strains are highly susceptible to VARV infection, establishing the first small animal model using VARV. In comparison, the non-humanized, immunosuppressed background mouse was not susceptible to systemic VARV infection. Following an intranasal VARV challenge that mimics the natural route for human smallpox transmission, the virus spread systemically within the humanized mouse before mortality (~ 13 days post infection), similar to the time from exposure to symptom onset for ordinary human smallpox. Our identification of a permissive/representative VARV animal model can facilitate testing of MCMs in a manner consistent with their intended use.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009633
DOI:
10.1371/journal.ppat.1009633.g001
DOI:
10.1371/journal.ppat.1009633.g002
DOI:
10.1371/journal.ppat.1009633.g003
DOI:
10.1371/journal.ppat.1009633.g004
DOI:
10.1371/journal.ppat.1009633.g005
DOI:
10.1371/journal.ppat.1009633.t001
DOI:
10.1371/journal.ppat.1009633.t002
DOI:
10.1371/journal.ppat.1009633.s001
DOI:
10.1371/journal.ppat.1009633.s002
DOI:
10.1371/journal.ppat.1009633.s003
DOI:
10.1371/journal.ppat.1009633.s004
DOI:
10.1371/journal.ppat.1009633.s005
DOI:
10.1371/journal.ppat.1009633.r001
DOI:
10.1371/journal.ppat.1009633.r002
DOI:
10.1371/journal.ppat.1009633.r003
DOI:
10.1371/journal.ppat.1009633.r004
DOI:
10.1371/journal.ppat.1009633.r005
DOI:
10.1371/journal.ppat.1009633.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1