Murine forebrain anomalies induced by coxsackievirus B3 variants

Abstract

Neonatal or 7-day-old mice inoculated intracranially with either of two temperature-sensitive mutants (ts1, ts6) or the parent coxsackievirus B3 (CVB3) subsequently developed porencephaly or hydranencephaly. The forebrain anomaly induced depended upon age of the animal at inoculation and virus variant inoculated. Sections of brains from hydranencephalic mice revealed severe meningeal reactions, necrotizing encephalitis, and liquifactive necrosis in the cerebrum. No pathology was found in the pons, medulla, or cerebellum. Immunofluorescence studies with hyperimmune anti-CVB3 antiserum showed a random distribution of virus-infected cells in the cerebrum. Virus was recovered from several organs but little to no interferon and no anti-CVB3 neutralizing antibody were present in brain tissues. Availability of cells for replication of virus at the time of inoculation and replicative properties of each virus likely contributed to the outcome. Thus, forebrain anomalies resembling those found in infants can be induced in a murine model by select variants of coxsackievirus B3.

Avian encephalomyelitis: A review

“…Higher antigen levels were detected in the heart, liver, pancreas and small intestines of birds infected with the field and vaccine strains than for the Van Roekel strains 3 to 10 days p.i., but antigen levels in the brain were comparable for all three strains. The predilection of non-adapted strains for the intestine, liver and pancreas and the growth of all three strains in chicken embryo heart muscle, suggests a pathogenesis similar to that of Coxsackie B3 viruses, which induce forebrain anomalies in neonatal and infant mice and infect a range of other gut-associated organs (Gaunt et al, 1984).…”

Coxsackievirus replication and the cell cycle: a potential regulatory mechanism for viral persistence/latency

“…Transmission of CV in humans is thought to occur through the fecal/oral route, due to poor sanitary conditions or direct contact of contaminated food and water. CV infections of humans can result in serious diseases such as myocarditis, pancreatitis and encephalitis, and coxsackievirus infection of mice recapitulates these human diseases [17,25,31]. CV RNA persists for many years in human tissues, as detected by RT-PCR [1,14,27], and RNA has also been identified long after infection in mice [39,40]; however, infectious virus has not been isolated and, especially in view of the assumed instability of RNA and the highly cytolytic nature of CV, the mechanism that underlies the long-term RNA persistence is unclear.…”

Coxsackievirus B3 and the Neonatal CNS

“…Forebrain abnormalities, including hydranencephaly, have been seen after infection of newborn human infants, as well as in experimental infections of neonatal mice. 15,16 Coxsackievirus-induced encephalitis may cause long-term damage to the CNS, including to the basal ganglia, leading to Parkinson-like symptoms, and memory and learning disorders suggestive of subcortical dementia; 17 indeed, CVB can cause a syndrome very similar to encephalitis lethargica, 18 a disease long considered viral in origin.…”