Characteristics of Viruses Derived from Nude Mice with Persistent Measles Virus Infection

Abstract

Measles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4-to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 ؋ 10 2 PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 ؋ 10 4 PFU of the Edmonston strain (P < 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics.

Molecular characterisation of virus in the brains of patients with measles inclusion body encephalitis (MIBE)

“…In measles virus from persistently infected brain, both in humans as well as in animal models, the nucleoprotein gene typically retains its function as this protein is required to form intact ribonuclear protein complexes to enable the virus to move from cell to cell in the brain [ 7 ]. The matrix protein, on the other hand, is usually highly mutated as this protein is not needed for replication in the brain [ 19 , 20 ]. Perhaps sufficient time had not elapsed for mutations to accumulate in this gene before the clinical presentation of MIBE in our highly immuno-compromised patients.…”

Measles Encephalitis: Towards New Therapeutics

“…Multiple murine models have been developed to address specific question about MeV pathogenesis, CNS invasion, antiviral treatments, and persistence (Table 1). Notably, MeV persistence has been demonstrated in mice infected with the Edmonston strain or a recombinant MeV expressing H from CAM/RB strain up to two months [140,141] and in nude mice with Edmonston strain highlighting the emergence of mutations [142]. SLAM transgenic (tg) ant CD46 tg mice models and derivates expressing stably and ubiquitously or not the human receptors for wt or vaccine MeV strains were also extensively used [143,144].…”

Advances in Antiviral Therapy for Subacute Sclerosing Panencephalitis

“…Among the 10 clones, when any 1 clone had an amino acid mutation at a position, it was counted as one mutation. Overlapping mutations at the same position in multiple clones were counted as a single mutation [ 33 ].…”

“…The measles virus isolated from the brains SSPE patients exhibits mutations specific to the M, F, and H genes (especially the M gen (Figure 1) and is characterized by neurocompatibility, neuropathogenicity, and a lack viral particle-forming ability [21,[30][31][32]. In-vivo studies using nude mice inoculated in t brain with the measles virus have also reported the accumulation of gene mutations, e pecially in the M gene, during persistent infection (Figure 2) [33]. On the other hand, cent studies have shown that many virus strains isolated from SSPE patients have subs tutions in the extracellular domain of the F protein, resulting in improved fusion activi Measles virus with hyperfusogenic mutant fusion proteins spreads between human ne rons in a cell-to-cell manner.…”