Key result
Mutant viruses isolated from the neuropathogenic mouse hepatitis virus srr7 acquired receptor-independent infectivity to neurons, leading to high neurovirulence and 100% mortality in mice within 7 days.
Mutant strains of the mouse hepatitis virus can infect cells independently of the major MHV receptor, which can be detected using spinoculation and UV radiation.
May signal neurovirulent coronavirus adaptation risk in models; leaves open relevance to human infections.
The mouse hepatitis virus (MHV) has a high mutation rate, leading to various neuropathologies after infection. The srr7 mutant was isolated from the MHV strain cl-2, which induces characteristic spongiform degeneration in the brain. To investigate outcomes of srr7 infection, we re-cloned srr7(H2) from the viral stock srr7(Mix). During this re-cloning, we obtained the mutant viruses, Mu-1, Mu-2, and Br-1 which was isolated from the mice brain infected with srr7(Mix). We examined mutant viruses for infectivity independent of the major MHV receptor (MHVR), because these mutants exhibited high virulence similar to cl-2, which is MHVR-independent. To confirm MHVR-independence in vitro, we used a combination of spinoculation and ultraviolet radiation to detect distinct plaque formation (SpinoPlaque(UV+)) afrer infection of BHK cells, which do not express MHVR. Using this technique, we found that the unique neuropathologies caused by infection with the mutant viruses result from infecting neurons, which do not express MHVR. Infection with the mutant viruses was 100% correlated with SpinoPlaque(UV+) formation. This is in contrast to infection with srr7, which does not from SpinoPlaque(UV+).
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Nomura et al. (2011) studied Neuropathogenic mouse hepatitis virus (MHV) infection (n=165). Mutant MHV viruses (Mu-1, Mu-2, Br-1) vs. srr7(H2) and cl-2 strains was evaluated on Receptor-independent infectivity and neurovirulence (survival rate). Mutant viruses isolated from the neuropathogenic mouse hepatitis virus srr7 acquired receptor-independent infectivity to neurons, leading to high neurovirulence and 100% mortality in mice within 7 days.
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