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Comparison of monkeypox viruses pathogenesis in mice by in vivo imaging.

Osorio JE, Iams KP, Meteyer CU, Rocke TE - PLoS ONE (2009)

Bottom Line: Intraperitoneal (IP) injection of both MPXV-Congo and MPXV-Congo/Luc+resulted in a systemic clinical disease and the same mean time-to-death at 9 (+/-0) days post-infection.Animals infected with the MPXV-USA/Luc+had less intense luminescence in tissues than those inoculated with MPXV-Congo/Luc+, and systemic spread of the MPXV-USA/Luc+virus occurred approximately two days later than the MPXV-Congo/Luc+.The ovary was an important target for viral replication as evidenced by the high viral titers and immunohistochemistry.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA. osorio@svm.vetmed.wisc.edu

ABSTRACT
Monkeypox viruses (MPXV) cause human monkeypox, a zoonotic smallpox-like disease endemic to Africa, and are of worldwide public health and biodefense concern. Using viruses from the Congo (MPXV-2003-Congo-358) and West African (MPXV-2003-USA-044) clades, we constructed recombinant viruses that express the luciferase gene (MPXV-Congo/Luc+and MPXV-USA-Luc+) and compared their viral infection in mice by biophotonic imaging. BALB/c mice became infected by both MPXV clades, but they recovered and cleared the infection within 10 days post-infection (PI). However, infection in severe combined immune deficient (SCID) BALB/c mice resulted in 100% lethality. Intraperitoneal (IP) injection of both MPXV-Congo and MPXV-Congo/Luc+resulted in a systemic clinical disease and the same mean time-to-death at 9 (+/-0) days post-infection. Likewise, IP injection of SCID-BALB/c mice with MPXV-USA or the MPXV-USA-Luc+, resulted in similar disease but longer (P<0.05) mean time-to-death (11+/-0 days) for both viruses compared to the Congo strains. Imaging studies in SCID mice showed luminescence in the abdomen within 24 hours PI with subsequent spread elsewhere. Animals infected with the MPXV-USA/Luc+had less intense luminescence in tissues than those inoculated with MPXV-Congo/Luc+, and systemic spread of the MPXV-USA/Luc+virus occurred approximately two days later than the MPXV-Congo/Luc+. The ovary was an important target for viral replication as evidenced by the high viral titers and immunohistochemistry. These studies demonstrate the suitability of a mouse model and biophotonic imaging to compare the disease progression and tissue tropism of MPX viruses.

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Histological sections from mice infected with MPXV-USA-2003 stained with hematoxylin and eosin.A) Necrosis of ovarian follicles (arrow) with subacute inflammation infiltrating surrounding connective tissue and peri-ovarian fat. B) Skin of foot with intradermal bulla containing edema and cell debris (arrow). Surrounding epidermis is undergoing ballooning degeneration.
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pone-0006592-g007: Histological sections from mice infected with MPXV-USA-2003 stained with hematoxylin and eosin.A) Necrosis of ovarian follicles (arrow) with subacute inflammation infiltrating surrounding connective tissue and peri-ovarian fat. B) Skin of foot with intradermal bulla containing edema and cell debris (arrow). Surrounding epidermis is undergoing ballooning degeneration.

Mentions: Consistent pathology was seen in the ovary, skin, and serosa of intestine sampled from SCID BALB/c mice infected IP with wt parental and recombinant MPXV-USA-2003 and MPXV-Congo clades. The ovary was severely necrotic with loss of architecture and subacute inflammation of surrounding tissues (Figure 7A). The wall of the ovarian bursa was thickened with neutrophils, macrophages and necrotic debris. Neutrophils, macrophages and red blood cells were also present in the open space of the ovarian bursa. The serosa of the intestine was mildly proliferative and occasionally associated necrosis of underlying smooth muscle. Multifocal lesions involving the skin of the feet and tail consisted of hyperkeratosis, acanthosis and subacute deep dermal inflammation. Eosinophilic cytoplasmic inclusion bodies, suggesting viral inclusions (Guarnieri bodies), were infrequently present in the vacuolated epithelium of the stratum spinosum of the hyperkeratotic skin (Fig. 6F). Intradermal bullae were filled with edema and scattered necrotic debris (Figure 7B) with ballooning degeneration of surrounding epithelium. Mild multifocal apoptosis was less consistently seen in liver and pancreas (data not shown).


Comparison of monkeypox viruses pathogenesis in mice by in vivo imaging.

Osorio JE, Iams KP, Meteyer CU, Rocke TE - PLoS ONE (2009)

Histological sections from mice infected with MPXV-USA-2003 stained with hematoxylin and eosin.A) Necrosis of ovarian follicles (arrow) with subacute inflammation infiltrating surrounding connective tissue and peri-ovarian fat. B) Skin of foot with intradermal bulla containing edema and cell debris (arrow). Surrounding epidermis is undergoing ballooning degeneration.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2719101&req=5

pone-0006592-g007: Histological sections from mice infected with MPXV-USA-2003 stained with hematoxylin and eosin.A) Necrosis of ovarian follicles (arrow) with subacute inflammation infiltrating surrounding connective tissue and peri-ovarian fat. B) Skin of foot with intradermal bulla containing edema and cell debris (arrow). Surrounding epidermis is undergoing ballooning degeneration.
Mentions: Consistent pathology was seen in the ovary, skin, and serosa of intestine sampled from SCID BALB/c mice infected IP with wt parental and recombinant MPXV-USA-2003 and MPXV-Congo clades. The ovary was severely necrotic with loss of architecture and subacute inflammation of surrounding tissues (Figure 7A). The wall of the ovarian bursa was thickened with neutrophils, macrophages and necrotic debris. Neutrophils, macrophages and red blood cells were also present in the open space of the ovarian bursa. The serosa of the intestine was mildly proliferative and occasionally associated necrosis of underlying smooth muscle. Multifocal lesions involving the skin of the feet and tail consisted of hyperkeratosis, acanthosis and subacute deep dermal inflammation. Eosinophilic cytoplasmic inclusion bodies, suggesting viral inclusions (Guarnieri bodies), were infrequently present in the vacuolated epithelium of the stratum spinosum of the hyperkeratotic skin (Fig. 6F). Intradermal bullae were filled with edema and scattered necrotic debris (Figure 7B) with ballooning degeneration of surrounding epithelium. Mild multifocal apoptosis was less consistently seen in liver and pancreas (data not shown).

Bottom Line: Intraperitoneal (IP) injection of both MPXV-Congo and MPXV-Congo/Luc+resulted in a systemic clinical disease and the same mean time-to-death at 9 (+/-0) days post-infection.Animals infected with the MPXV-USA/Luc+had less intense luminescence in tissues than those inoculated with MPXV-Congo/Luc+, and systemic spread of the MPXV-USA/Luc+virus occurred approximately two days later than the MPXV-Congo/Luc+.The ovary was an important target for viral replication as evidenced by the high viral titers and immunohistochemistry.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA. osorio@svm.vetmed.wisc.edu

ABSTRACT
Monkeypox viruses (MPXV) cause human monkeypox, a zoonotic smallpox-like disease endemic to Africa, and are of worldwide public health and biodefense concern. Using viruses from the Congo (MPXV-2003-Congo-358) and West African (MPXV-2003-USA-044) clades, we constructed recombinant viruses that express the luciferase gene (MPXV-Congo/Luc+and MPXV-USA-Luc+) and compared their viral infection in mice by biophotonic imaging. BALB/c mice became infected by both MPXV clades, but they recovered and cleared the infection within 10 days post-infection (PI). However, infection in severe combined immune deficient (SCID) BALB/c mice resulted in 100% lethality. Intraperitoneal (IP) injection of both MPXV-Congo and MPXV-Congo/Luc+resulted in a systemic clinical disease and the same mean time-to-death at 9 (+/-0) days post-infection. Likewise, IP injection of SCID-BALB/c mice with MPXV-USA or the MPXV-USA-Luc+, resulted in similar disease but longer (P<0.05) mean time-to-death (11+/-0 days) for both viruses compared to the Congo strains. Imaging studies in SCID mice showed luminescence in the abdomen within 24 hours PI with subsequent spread elsewhere. Animals infected with the MPXV-USA/Luc+had less intense luminescence in tissues than those inoculated with MPXV-Congo/Luc+, and systemic spread of the MPXV-USA/Luc+virus occurred approximately two days later than the MPXV-Congo/Luc+. The ovary was an important target for viral replication as evidenced by the high viral titers and immunohistochemistry. These studies demonstrate the suitability of a mouse model and biophotonic imaging to compare the disease progression and tissue tropism of MPX viruses.

Show MeSH
Related in: MedlinePlus