Approaches in the Understanding of Morbillivirus Neurovirulence

Abstract

Certain members of the morbillivirus genus, canine distemper virus, phocine distemper virus, and the cetacean viruses of dolphins and porpoises exhibit high levels of central nervous system (CNS) infection in their natural hosts. CNS complications are rare for measles virus (MV) and are not associated with rinderpest virus (RPV) and peste des petits ruminants virus (PPRV) infection. However, both RPV and PPRV are neurovirulent in permissive murine strains. Human postmortem tissue, neural cell cultures, and animal models have been used to answer major questions concerning morbillivirus neurovirulence. Studies of the MV CNS complication subacute sclerosing panencephalitis (SSPE) indicate that virus could enter the CNS either by direct infection of endothelial cells or in infected leucocytes, followed by infection of predominately neurones and oligodendrocytes. It has been established that MV neurovirulence in mice is partially determined by the virus-receptor specificity. The two known MV receptors, CD46 and SLAM, have been examined in normal and SSPE brain tissue and the findings suggest that further receptors may be necessary to explain infection of the CNS with wild-type strains of MV. In both humans and mice (and in vitro), once infection of neurones has been established, virus spreads transneuronally. It is possible that all morbilliviruses transiently infect the CNS in their natural hosts, but development of disease is dependent on the efficiency of the immune response. Alternatively, for RPV and PPRV, virus entry may be restricted due either to absence of viral receptors or failure of virus to replicate or spread in the CNS.

Natural Peste des Petits Ruminants Virus Infection: Novel Pathologic Findings Resembling Other Morbillivirus Infections

“…29 Neurovirulence of the morbilliviruses, including canine distemper virus and phocine distemper virus, is described in detail. 11,19,20,33 All morbilliviruses can infect the central nervous system, but some morbilliviruses are easily eliminated by the developing host immunity, and temporary central nervous system infection occurs. 11,16 The entrance of the morbilliviruses into any cell is dependent on the immune status of the host and virus-specific receptors, such as membrane cofactor protein CD46.…”

“…11,19,20,33 All morbilliviruses can infect the central nervous system, but some morbilliviruses are easily eliminated by the developing host immunity, and temporary central nervous system infection occurs. 11,16 The entrance of the morbilliviruses into any cell is dependent on the immune status of the host and virus-specific receptors, such as membrane cofactor protein CD46. 15,16 However, rinderpest virus and PPRV neurovirulence still remains an obscure entity because of insufficient data available.…”

“…5) 6,9,11,19,20), was lymphoid depletion. Syncytial cells, eosinophilic debris, and intranuclear inclusion bodies were also noted in the affected lymphoid tissues (Fig.…”

“…Multifocal pale areas were evident at the cut surfaces of the liver in 6 cases (case Nos. 1,11,13,17,19,21).…”

“…2,32 Little is known about the resemblance of the pathologic findings of PPRV infection to those resulting from the other morbillivirus infections in terms of lesions in the central nervous system, kidney, and abomasum. 11,21,28,32,33 The first PPRV infection in Turkey was reported in 4 sheep 2 , and since then many outbreaks have been reported. 23,24,32,34 Ö zkul et al 24 isolated PPR viruses from 2 separate field cases in Turkey.…”