Immunocompetent mouse model for Crimean-Congo hemorrhagic fever virus
- Laboratory of Virology, Division of Intramural Research, NIAID, NIH, United States
- Texas Veterinary Pathology, United States
- Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, United States
Figures
Figure 1 with 3 supplements
MA-CCHFV causes overt clinical disease in wild-type (WT) mice.
(A and B) Groups of 8-week-old male (A) or female (B) WT C57BL/6J mice were infected with 10,000 TCID50 of MA-CCHFV or CCHFV Hoti via the intraperitoneal (IP) route and weighed daily. (A and B) Male …
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Figure 1—source data 1
Source data for Figure 1.
- https://cdn.elifesciences.org/articles/63906/elife-63906-fig1-data1-v2.xlsx
Figure 1—figure supplement 1
Passage of Crimean-Congo hemorrhagic fever virus (CCHFV) in mice.
(A–B) Rag1-/- mice, passages 1–9 or wild-type (WT) C57BL6/J mice, passages 10 and 11, were inoculated with indicated source of passaged CCHFV and weighed (A). N = 1 mouse per passage. (C-D) WT …
Figure 1—figure supplement 2
Male versus female mice infected with MA-CCHFV.
Eight-week-old WT MA-CCHFV were infected with 10,000 TCID50 of MA-CCHFV via the intraperitoneal (IP) route and weighed daily. Data in this figure is duplicated from main text Figure 1A and B and …
Figure 1—figure supplement 3
Seroconversion of dose-finding study.
Eight-week-old wild-type (WT) C57BL6/J mice were infected with indicated dose of MA-CCHFV and seroconversion at 14 DPI evaluated using whole virion ELISA. Total CCHFV-specific Ig measured in a 1:400 …
Figure 2 with 1 supplement
MA-CCHFV causes clinical disease in multiple laboratory strains of mice.
(A–E) Groups of 8-week-old male or female mice of indicated strains were infected with 1000 TCID50 of MA-CCHFV via the intraperitoneal (IP) route and weighed daily. N = 5 mice per group. Data shown …
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Figure 2—source data 1
Source data for Figure 2.
- https://cdn.elifesciences.org/articles/63906/elife-63906-fig2-data1-v2.xlsx
Figure 2—figure supplement 1
Lethal infection of young mice with MA-CCHFV.
Three-week-old wild-type (WT) C57BL6/J mice were inoculated with 10,000 TCID50 of MA-CCHFV. Mice were weighed daily (A) and humanely euthanized when they acchieved euthanasia criteria (B). N = 5 …
Figure 3
MA-CCHFV replicates to high titers of multiple tissues in wild-type (WT) mice.
Groups of 8-week-old WT C57BL/6J mice were infected with 10,000 TCID50 of MA-CCHFV or CCHFV Hoti via the intraperitoneal (IP) route. At indicated time points, mice were necropsied and viral RNA …
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Figure 3—source data 1
Source data for Figure 3.
- https://cdn.elifesciences.org/articles/63906/elife-63906-fig3-data1-v2.xlsx
Figure 4 with 1 supplement
MA-CCHFV causes severe pathology in the livers of WT mice.
(A–D) Groups of 8-week-old wild-type (WT) mice were infected were infected with 10,000 TCID50 of MA-CCHFV or Hoti via the intraperitoneal (IP) route or mock-infected. (A) Representative liver …
Figure 4—figure supplement 1
Histology and IHC of spleens from MA-CCHFV infected mice.
Groups of 8-week-old wild-type (WT) mice were infected were infected with 10,000 TCID50 of MA-CCHFV via the intraperitoneal (IP) route or mock-infected. (A) Representative spleen sections from a …
Figure 5 with 1 supplement
MA-CCHFV infection results in inflammatory cytokine responses in wild-type (WT) mice.
Eight-week-old male or female WT mice were infected with 10,000 TCID50 MA-CCHFV via the intraperitoneal (IP) route or mock-infected. At indicated timepoints, cytokine levels in the plasma was …
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Figure 5—source data 1
Source data for Figure 5.
- https://cdn.elifesciences.org/articles/63906/elife-63906-fig5-data1-v2.xlsx
Figure 5—figure supplement 1
Complete cytokine profile of mock, Hoti, or MA-CCHFV-infected mice.
Eight-week-old wild-type (WT) C57BL6/J mice were infected with 10,000 TCID50 of MA-CCHFV or Hoti or mock-infected. At indicated timepoints mice were euthanized and plasma cytokine levels evaluated …
Figure 6
Type I IFN is required for survival following MA-CCHFV infection.
(A–B) Eight-week-old male or female wild-type (WT) mice were infected with 10,000 TCID50 of CCHFV Hoti, MA-CCHFV via the intraperitoneal (IP) route or mock-infected. At indicated timepoints, plasma …
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Figure 6—source data 1
Source data for Figure 6.
- https://cdn.elifesciences.org/articles/63906/elife-63906-fig6-data1-v2.xlsx
Figure 7
MA-CCHFV is lethal in mice lacking adaptive immunity.
(A–C) Groups of 8-week-old wild-type (WT) mice were infected were infected with 10,000 TCID50 of MA-CCHFV via the intraperitoneal (IP) route or mock-infected. At indicated timepoints CCHFV-specific …
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Figure 7—source data 1
Source data for Figure 7.
- https://cdn.elifesciences.org/articles/63906/elife-63906-fig7-data1-v2.xlsx
Author response image 1
Tables
Table 1
Mutations identified in MA-CCHFV.
| Mutant Frequency (%) | % AA Conservation among | ||||||
|---|---|---|---|---|---|---|---|
| Segment | SNP (Hoti>Mutant) | Coding Change (Hoti>Mutant) | Domain | Passage 4 | Passage 9 | MA-CCHFV | CCHFV Strains |
| S | A739G | NP I228M | Arm | 93 | 87 | 88 | 100 (I) |
| A806G | NP K251E and NSs F26S | Arm and Unknown | 95 | 100 | 99 | NP 100 (K); NSs 88 (L), 12 (F) | |
| M | A1502G | R475R | GP38 | 3 | 35 | 54 | |
| G2671A | C865Y | NSm | 100 | 100 | 100 | 100 (C) | |
| T4068C | L1331L | Gc | 98 | 100 | 100 | ||
| L | G6097A | S2007N | Unknown | 83 | 97 | 98 | 71 (S), 29 (N) |
| C8135T | V2686V | RdRp | 83 | 95 | 96 | ||
| C9919T | P3281L | Unknown | 85 | 96 | 96 | 100 (P) | |
| G11618A | E3847E | Unknown | 85 | 98 | 97 | ||
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Other | Hoti | This paper | Virus strain | |
| Other | MA-CCHFV | This paper | Virus strain |
Additional files
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Supplementary file 1
Complete histological and IHC findings of formalin-fixed tissue sections from CCHFV-infected mice.
- https://cdn.elifesciences.org/articles/63906/elife-63906-supp1-v2.xlsx
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Supplementary file 2
Complete blood chemistry of CCHFV-infected mice.
- https://cdn.elifesciences.org/articles/63906/elife-63906-supp2-v2.xlsx
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Transparent reporting form
- https://cdn.elifesciences.org/articles/63906/elife-63906-transrepform-v2.docx
