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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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In vivo imaging of MPXV-Congo-Luc+ (left panel) and MPXV-USA-Luc+ (right panel) in SCID- BALB/c mice (Intraperitoneal inoculation).A group of four, 4-week-old SCID BALB/c mice was inoculated by the IP route with 105 PFU of MPXV-USA-Luc+virus and imaged as described as described in materials and methods. An uninfected negative control animal (on left) was also injected with luciferin and imaged on the same times as infected animals. Ventral view.
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pone-0006592-g003: In vivo imaging of MPXV-Congo-Luc+ (left panel) and MPXV-USA-Luc+ (right panel) in SCID- BALB/c mice (Intraperitoneal inoculation).A group of four, 4-week-old SCID BALB/c mice was inoculated by the IP route with 105 PFU of MPXV-USA-Luc+virus and imaged as described as described in materials and methods. An uninfected negative control animal (on left) was also injected with luciferin and imaged on the same times as infected animals. Ventral view.

Mentions: In SCID- BALB/c mice, luminescence indicative of MPXV infection was also visible as early as 24 hours PI and limited at that time to the peritoneal cavity (Figure 3). Once again, infection with the MPXV-Congo-Luc+produced a more intense luminescent signal, and by 96 hours PI, it had spread to other organs and tissues in the abdominal region, the thoracic area, and axillary lymph nodes. At 168 hours PI, luminescent signal was detected in the entire body and animals died between 192 and 216 hours PI. In SCID mice inoculated with MPXV-USA/Luc+, luminescent signal was also visible in the abdominal region at 96 hours PI, and it was visible in the tail, feet, and nasal area at 240 hours PI. All of these animals died by 264 hours PI.


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

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

In vivo imaging of MPXV-Congo-Luc+ (left panel) and MPXV-USA-Luc+ (right panel) in SCID- BALB/c mice (Intraperitoneal inoculation).A group of four, 4-week-old SCID BALB/c mice was inoculated by the IP route with 105 PFU of MPXV-USA-Luc+virus and imaged as described as described in materials and methods. An uninfected negative control animal (on left) was also injected with luciferin and imaged on the same times as infected animals. Ventral view.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006592-g003: In vivo imaging of MPXV-Congo-Luc+ (left panel) and MPXV-USA-Luc+ (right panel) in SCID- BALB/c mice (Intraperitoneal inoculation).A group of four, 4-week-old SCID BALB/c mice was inoculated by the IP route with 105 PFU of MPXV-USA-Luc+virus and imaged as described as described in materials and methods. An uninfected negative control animal (on left) was also injected with luciferin and imaged on the same times as infected animals. Ventral view.
Mentions: In SCID- BALB/c mice, luminescence indicative of MPXV infection was also visible as early as 24 hours PI and limited at that time to the peritoneal cavity (Figure 3). Once again, infection with the MPXV-Congo-Luc+produced a more intense luminescent signal, and by 96 hours PI, it had spread to other organs and tissues in the abdominal region, the thoracic area, and axillary lymph nodes. At 168 hours PI, luminescent signal was detected in the entire body and animals died between 192 and 216 hours PI. In SCID mice inoculated with MPXV-USA/Luc+, luminescent signal was also visible in the abdominal region at 96 hours PI, and it was visible in the tail, feet, and nasal area at 240 hours PI. All of these animals died by 264 hours PI.

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