Dosage comparison of Congo Basin and West African strains of monkeypox virus using a prairie dog animal model of systemic orthopoxvirus disease

Abstract

The prairie dog is valuable for the study of monkeypox virus (MPXV) virulence and closely resembles human systemic orthopoxvirus disease. Herein, we utilize a variable dose intranasal challenge with approximately 10(3), 10(4), 10(5), and 10(6)PFU for each clade to further characterize virulence differences between the two MPXV clades. A trend of increased morbidity and mortality as well as greater viral shedding was observed with increasing viral challenge dose. Additionally, there appeared to be a delay in onset of disease for animals challenged with lower dosages of virus. Mathematical calculations were used to determine LD(50) values and based on these calculations, Congo Basin MPXV had approximately a hundred times lower LD(50) value than the West African clade (5.9x10(3) and 1.29x10(5) respectively); reinforcing previous findings that Congo Basin MPXV is more virulent.

Fig. 1

West African MPXV: individual animal percent weight change. Groups of prairie dogs (n = 4) were inoculated with 6 × 10² (A), 6 × 10³ (B), 6 × 10⁴ (C), or 6 × 10⁵ (D) PFU of West African MPXV via an IN route.

Fig. 2

Groups of prairie dogs (n = 4) were inoculated with 6 × 10², 6 × 10³, 6 × 10⁴, or 6 × 10⁵ PFU of West African MPXV via an IN route. The lesion progression for one animal in the West African 6 × 10³ PFU group is shown beginning on day 10 p.i.

Fig. 3

Congo Basin MPXV: individual animal percent weight change. Groups of prairie dogs (n = 4) were inoculated with 8 × 10² (A), 8 × 10³ (B), 8 × 10⁴ (C), or 8 × 10⁵ (D)PFU of Congo Basin MPXV via an IN route.

Fig. 4

West African MPXV viable virus results for oral swabs. Groups of prairie dogs (n = 4) were inoculated with 6 × 10² (A), 6 × 10³ (B), 6 × 10⁴ (C), or 6 × 10⁵ (D) PFU of West African MPXV via an IN route. Oral swabs were taken twice a week and subsequently tested for infectious virus. Values are shown on a log scale.

Fig. 5

Peak mean viral load for oral swabs. Groups of prairie dogs (n = 4) were inoculated with one of four dosages of either West African MPXV (A) or Congo Basin MPXV (B) via an IN route. Oral swabs were taken twice a week and subsequently tested for infectious virus. Values are shown on a log scale. Error bars, SD.

Fig. 6

West African MPXV viable virus results for necropsy samples. Groups of prairie dogs (n = 4) were inoculated with 6 × 10², 6 × 10³ (A), 6 × 10⁴ (B), or 6 × 10⁵ (C) PFU of West African MPXV via an IN route. If death did not occur, animals were euthanized 31–34 days p.i. and necropsies performed. Results are shown on a log scale for those animals which yielded infectious viral samples.

Fig. 7

Serology results for MPXV infected prairie dogs. Groups of prairie dogs were inoculated with either West African MPXV (A) or Congo Basin MPXV (B) via an IN route. Serum samples were taken upon death or at time of necropsy (except PD34 which could not have blood collected post mortem). OD values for OPXV antibodies are shown for each dosage group. Asterisks next to an animal number indicate an animal that perished or was euthanized during the study.

Fig. 8

Congo Basin MPXV viable virus results for oral swabs. Groups of prairie dogs (n = 4) were inoculated with 8 × 10² (A), 8 × 10³ (B), 8 × 10⁴ (C), or 8 × 10⁵ (D) PFU of Congo Basin MPXV via an IN route. Oral swabs were taken twice a week and subsequently tested for infectious virus. Values are shown on a log scale for animals which yielded infectious viral samples.

Fig. 9

Congo Basin viable virus results for necropsy tissues. Groups of prairie dogs (n = 4) were inoculated with 8 × 10² (A), 8 × 10³ (B), 8 × 10⁴ (C), or 8 × 10⁵ (D) PFU of Congo Basin MPXV via an IN route. If death did not occur, animals were euthanized 31–34 days p.i. and necropsies performed. Results are shown for those animals which yielded infectious viral samples on a log scale.