Table 1.
Timeline of dam inoculation, blood draw, skin lesion counts, fetal heart rate measurement, and skin lesion swab schedule.
Fig 1.
Maternal systemic MPXV infection.
(A) Whole blood MPXV DNA viral loads. (B) Skin lesion counts. (C) MPXV DNA viral loads in eluates from swabbed skin lesions. (D) Infectious virus titers in eluates from swabbed skin lesions measured by plaque assay at 7 days post-inoculation. (E) Maternal weight change compared to starting weight, with days where oral gavage feeds were administered noted as white-filled circles. (F) Maternal temperature, with the normal temperature range shown between the dashed lines.
Fig 2.
MPXV tissue and body fluid viral loads.
MPXV viral loads were measured at the time of necropsy in fetal, maternal, and maternal-fetal interface (MFI) tissues (A) and body fluids (B). Cerebrospinal fluid (CSF), lymph node (LN), frontal lobe (FL), hippocampus (HC). The average viral load with standard deviation is shown for placental discs and skin because multiple biopsies were obtained for those tissues. For ID 103, bars are below 100 to indicate viral DNA was below the limit of detection.
Fig 3.
MPXV mRNA and antigen localization within maternal-fetal interface tissues by ISH and IHC.
Representative images from ID 101 and 102 are presented. Fetal membranes (A-D), chorionic plate (E-H), decidua basalis (I-L), and placental villi (M-P) are shown. Images of the full tissue sections from which each of these photomicrographs were derived are shown in S4 and S5 Figs.
Fig 4.
MPXV co-localizes with cell-specific markers in the placental villi.
(A) MPXV co-localizes with CD163, a Hofbauer cell marker. MPXV is seen in few Hofbauer cells (CD163 staining) within the villi (not the majority of Hofbauer cells). (B) MPXV co-localization with vimentin, a marker for villous stromal cells. (C) MPXV co-localization with CD31, an endothelial cell marker which is also expressed on the apical surface of rhesus syncytiotrophoblasts. Representative placental images from ID 101 are shown.
Fig 5.
MPXV does not cause villitis or decidual vasculitis.
(A) The placentas of IDs 101 and 102 demonstrated areas of villous stromal histiocytic accumulation associated with MPXV detection by ISH (red chromogen, arrow heads). The placental epithelium and endovascular extravillous trophoblasts invading the decidual spiral arteries (square) are negative for virus (arrow). There is no acute or chronic villitis (B) and the decidual spiral arteries are negative for leukocytoclastic vasculitis (arrow) (C). One of the animals (101) showed focal decidual necrosis (D) that co-labeled for MPXV virus (arrows outlining brown chromogen, E). * is a landmark in the upper right corner of panel A to compare image in A (2.5x objective) with image B (10x obj). Images C-E were all photographed with 10x objective.
Fig 6.
Multiple regions within the head from the fetus of ID 101 (A) show ISH signal. The dotted line shows the head shape. Note: an area of neuropil was removed for viral load measurements. ISH signal was noted in the skin (B), in the subventricular zone of the anterior horn (C) and the posterior horn (D) of the lateral ventricle, and in the medial neuropil (E). Multiple regions within the torso from the fetus of ID 102 (F) show ISH signal. The dotted line shows the torso shape. ISH signal was found in the lung (G), intercostal muscles (H), liver (I), and in the meninges and dura surrounding the spinal cord (J).