Poliomyelitis in MuLV-infected ICR-SCID mice after injection of basement membrane matrix contaminated with lactate dehydrogenase-elevating virus

Abstract

The arterivirus lactate dehydrogenase-elevating virus (LDV) causes life-long viremia in mice. Although LDV infection generally does not cause disease, infected mice that are homozygous for the Fv1(n) allele are prone to develop poliomyelitis when immunosuppressed, a condition known as age-dependent poliomyelitis. The development of age-dependent poliomyelitis requires coinfection with endogenous murine leukemia virus. Even though LDV is a common contaminant of transplantable tumors, clinical signs of poliomyelitis after inadvertent exposure to LDV have not been described in recent literature. In addition, LDV-induced poliomyelitis has not been reported in SCID or ICR mice. Here we describe the occurrence of poliomyelitis in ICR-SCID mice resulting from injection of LDV-contaminated basement membrane matrix. After exposure to LDV, a subset of mice presented with clinical signs including paresis, which was associated with atrophy of the hindlimb musculature, and tachypnea; in addition, some mice died suddenly with or without premonitory signs. Mice presenting within the first 6 mo after infection had regions of spongiosis, neuronal necrosis and astrocytosis of the ventral spinal cord, and less commonly, brainstem. Axonal degeneration of ventral roots prevailed in more chronically infected mice. LDV was identified by RT-PCR in 12 of 15 mice with typical neuropathology; positive antiLDV immunolabeling was identified in all PCR-positive animals (n = 7) tested. Three of 8 mice with neuropathology but no clinical signs were LDV negative by RT-PCR. RT-PCR yielded murine leukemia virus in spinal cords of all mice tested, regardless of clinical presentation or neuropathology.

Figure 1.

Histopathology of mice presenting with paresis (mice presenting in the first 6 mo) (A) Cross-section of caudal lumbar spinal cord. A focal well-circumscribed region of malacia is present in the ventral horn (arrows). Hematoxylin and eosin stain; bar, 20 μm. (B) Cross-section of midlumbar spinal cord. Immunoreactive astrocytes are limited to regions corresponding to malacia in the ventral horns (arrows). AntiGFAP immunohistochemistry; bar, 20 μm. (C) Ventral horn, spinal cord. A dying neuron with swollen granular cytoplasm and a pale nucleus is indicated (arrow). Hematoxylin and eosin stain; bar, 5 μm. (D) Ventral horn, spinal cord. Numerous hypertrophic astrocytes with dense eosinophilic cytoplasm are indicated (arrows). Hematoxylin and eosin stain; bar, 5 μm. (E) Ventral horn, spinal cord. Strongly immunoreactive hypertrophic astrocytes with thick processes and abundant cytoplasm are indicated (arrows). AntiGFAP immunohistochemistry; bar, 5 μm. (F) Ventral horn, spinal cord. Omission of the primary antibody confirms lack of nonspecific immunoreactivity from the secondary antibody. Negative control, antiLDV immunohistochemistry; bar, 5 μm. (G) Dorsal horn, spinal cord. Dorsal horn regions lacking evidence of pathology also fail to demonstrate antiLDV immunoreactivity. AntiLDV immunohistochemistry; bar, 5 μm. (H) Ventral horn, spinal cord. AntiLDV immunoreactivity is noted within vacuolated cytoplasm of a degenerating neuron (thick arrow) as well as within astrocytes (small arrows). AntiLDV immunohistochemistry; bar, 5 μm.

Figure 2.

Histopathology of mice presenting with paresis (mice presenting after 6 mo) (A) Ventral horn, spinal cord. Marked regional axonal degeneration of ventral roots is evident (arrow). Hematoxylin and eosin stain; bar, 50 μm. (B) Ventral root, spinal cord: boxed area from A. Small numbers of mononuclear cells admixed with occasional neutrophils infiltrate degenerate ventral roots (arrow). Hematoxylin and eosin stain; bar, 50 μm.