Table 2.
Mice used in the study of MPXV
| Animal species | Strain | Age | Viral strain | Route of infection/dose | Major findings | Reference |
|---|---|---|---|---|---|---|
| Mouse (Mus muscullus) | a | Adults and 2-day-old | Egg passage material of the monkey agent | Intracerebral and intranasal/agent diluted 104 | Adult mice inoculated intracerebrally showed signs of encephalitis followed by 100% lethality. Two-day-old infant mice inoculated intranasally showed 100% lethality | (Magnus et al.1) |
| C57BL/6, SCID, DBA, A/Ncr, C3HeJ, IFN-γR−/−, BALB/c, IFN-α/βR−/−, 129 stat1−/−, C57BL/6 stat1−/− | 6- to 12-week-old | MPXV-ZAI-79 | Intranasal/a and footpad 102–104 p.f.u/mL | Footpad inoculation in adult mice was not efficient in infecting strains characterized as not responding to IFN-1 or type-2-dependent signaling pathways, on the other hand, infection occurred satisfactorily in C57BL/6 stat1−/− and 129 stat1−/− mice. In contrast, the immunodeficient SCID strain was susceptible to an intranasal MPXV infection, as were C57BL/− and 129 stat1−/− 129 stat1−/−. Overall, high mortality was a feature observed in STAT1-deficient mice, in addition to weight loss and viral presence in internal organs | (Stabenow et al.46) | |
| CAST/EiJ, C57BL/6, B6.129S7-IFNγ, BALB/c | a | MPXV-Z79-I-005 and MPXV-Z79-CB2 | Intranasal102–106 p.f.u/mL | MPXV replicated in the lungs to previous titers from other sites in CAST/EiJ mice. Surprisingly, lung titers in dose-infected BALB/c mice were similar to titers in CAST/EiJ mice, although all mice survived. Animals without IFN-γ, treated by gravity, or left by weight presented an upright posture and became moribund. In contrast, similar disease symptoms were delayed and markedly less pronounced in the animals that received IFN-γ, and these animals fully recovered. Inoculation of IFN in CAST/EiJ mice led to protection against MPXV. In addition, C57BL/6 mice with inactivation of the IFN gene or the IFN receptor gene are more sensitive to the disease | (Earl et al.47) | |
| a | 2-, 8-, 12-, and 15-day-old | Copenhagen | Intraperitoneal and intranasal/1,2x106 p.f.u/mL, footpad/6x102 p.f.u/mL and oral/a | When inoculated intraperitoneally, all animals showed similar symptoms and occurred as a result of infection, whereas 50% died infected via the footpad and 40% died orally. Sequential evaluations showed that the virus can be found in the blood, lungs, liver, spleen, and kidneys, with considerable amounts of virus detected in the lungs and other organs in the acute phase of the disease | (Marennikova and Seluhina,48) | |
| BALB/c and SCID | 3- to 4-week-old | MPXV-2003-USA-044 and MPXV-Congo-Luc+ | Intraperitoneal/a | In BALB/c mice, the luminescent signal had the highest peaks between 96 and 120 h. Greater replication and faster dissemination were observed mainly to organs of the peritoneal cavity, with eventual dissemination to axillary lymph. In SCID mice, a more intense luminescent light was observed after 96 h. It was spread to organs and tissues in the regions of the abdominal, thoracic, and axillary lymph nodes, in addition to showing visible signs in the tail, feet, and nasal region. Biophotonic images also revealed the tropism of MPXV for ovarian tissues | (Osorio et al.49) | |
| CAST/EiJ and BALB | 9-week-old | MPXV-z06 and MPXV-z79-CB2 | Intranasal/a | High luminescence in the nasal area with a peak between 7 and 12 days after infection was observed in the animals. With the recombinant strain MPXV-z79-CB2, CAST/EiJ mice infected intranasally showed lethargy, hunched posture, ruffled hair, and severe weight loss | (Earl et al.50) | |
| ICR | 8- to 10-day-old | MPXV-Z79-I-005 | Intranasal/104–105 p.f.u/mL | Mice by MPXV accumulations of nasal, lung, and brain pathogens. The presence and replication in primary target cells and traditional observations of MPXV (mononuclear phagocytic cells and tract epitheliocytes) are present, as well as some other cell types (endothelial cells, reticular cells, connective tissue cells) were also observed | (Sergeev et al.51) | |
| 129S1/SvlmJ, A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, CAST/EiJ (WD), DBA/2J, FVB/NJ, SJL/J, SPRET/EiJ (WD), AKR/J, C57 L/J, C58/J, MOLF/EiJ (WD), NOD/ShiLtJ, NZB/BINJ, PERA/EiJ(WD), PL/J, SM/J, SWR/J, BUB/BnJ, C57BL/10J, C57BLKS/J, CBA/J, CZECHII/EiJ (WD), LP/J, RIIIS/J, WSB/EiJ (WD), BTBR T+ tf/J, C57BR/cdJ, CE/J, I/LnJ, MA/MyJ, NON/ShiLtJ, NZW/LacJ, PWK/PhJ (WD), SEA/GnJ and BALB/c | 4- to 8- week-old and 5- to 11-month- old | MPXV-Z79-I-005 and MPXV-USA-2003-044 | Intranasal and intraperitoneal/102–106 p.f.u/mL | Thirty-eight inbred mouse strains were tested for MPXV susceptibility. Three strains were developed, from which CAST/ were developed. CAST/EiJ exhibit weight loss, morbidity, and death in a dose-dependent manner, whereas there were no deaths of BALB/c mice at high doses. Both routes of inoculation resulted in replication in the spleen | (Americo et al.52) | |
| CAST/EiJ, C57BL/6, B6:129X1-Il15ratm1Ama/J and B6-129X1 | 9- to 13-week-old | MPXV-z06 | Intraperitoneal/a | Administration of IL-15 to CAST mice transiently increased NK and CD8+ T cells that could express IFN-γ, indicating that progenitor cells were able to respond to cytokines. However, the number of NK cells rapidly decreased, indicating a defect in their homeostasis. In addition, antibodies to interferon-γ abrogated the protection by activated NK cells. Thus, the inherent susceptibility of CAST mice to orthopoxviruses may be explained by a low level of natural killer (NK) cells | (Earl et al.53) | |
| C57BL/6J, CAST/EiJ, MOLF/EiJ, C58/J, NZW/Lacj, CASA/Rkj and BALB/c | a | MPXV-Z79-CB2 and MPXV-Z79-005 | Intranasal/104–106 p.f.u/mL | NZW/Lac and C58 mice exhibited more weight loss than other classical inbred strains, but all survived intranasal MPXV challenges. Mice from three naturally derived strains, in addition to CAST, exhibited severe weight loss and died or were euthanized | (Earl et al.54) | |
| C57BL/6 and BALB/c | 6- to 7-week-old | MPXV-2003-044 and MPXV-2003-358 | Footpad and intranasal/ 105 p.f.u/mL | Mice inoculated on the footpad with the Congo Basin strain showed clinical signs of the disease, with BALB/c mice showing greater edema compared with C57BL/6 mice. One mouse of the BALB/c strain showed weight loss, whereas no mouse of the C57/BL6 strain showed this clinical sign. When inoculation took place intranasally, weight loss was observed in both strains of mice. On the other hand, mice inoculated on the footpad with MPXV from West Africa showed only mild swelling at the inoculation site. None of the mice in the group inoculated with intranasal MPXV from West Africa developed any obvious signs of morbidity | (Hutson et al.44) | |
| CAST/EiJ mice | 4- to 6-week-old | 2022 MPXV isolate (SP2833) | Inhalation/104 or 106 PFU | Although the virus replicated efficiently in the respiratory tract, mice did not succumb to the infection | (Warner et al.55) |
a
Not reported; p.f.u: plaque formation unit; mL: milliliter; MPXV: monkeypox virus.