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Characterization of JHMV variants isolated from rat brain and cultured neural cells after wild type JHMV infection
Abstract:
After intracerebral inoculation of wild type (wt) JHMV into 4 to 5 week-old Lewis rats, only variants with larger mRNA3 were selectively propagated and no wt JHMV was reisolated from the brain. Detailed analysis of a cloned virus from infected rat brain, c1-2, showed that the virus had larger mRNAs 2, 2a and 3 as compared with those of wt JHMV, while there was no such difference for other mRNAs. The E2 glycoprotein of a variant virus was also shown to be larger as compared with that of wt JHMV. Such selective replication of variants were also observed in neural cell culture after infection with wt JHMV. However, these variants isolated from the brain of infected rat (c1-2) and from infected neural cells (CNS virus) differed from each other in the amounts of mRNAs 2 and 2a as well as 65 K protein. All of these data suggest that the viruses with larger E2 glycoprotein have the growth advantage in rat brain cells, which could be responsible for acute encephalitis of rats after infection with wt JHMV.
Insights
Wild-type JHMV infection in rats selectively propagates variants with larger mRNA3 and E2 glycoprotein. These variants show a growth advantage in rat brain cells, potentially causing acute encephalitis.
Area of Science:
- Virology
- Neuroscience
- Molecular Biology
Background:
- Murine hepatitis virus (MHV), specifically JHMV, is a neurotropic coronavirus.
- JHMV infection in susceptible hosts like Lewis rats can lead to acute encephalitis.
Purpose of the Study:
- To investigate the viral variants that propagate after intracerebral JHMV inoculation in Lewis rats.
- To understand the molecular basis for viral adaptation and pathogenesis in the rat central nervous system.
Main Methods:
- Intracerebral inoculation of wild-type JHMV into Lewis rats.
- Isolation and characterization of viral variants from infected rat brains and neural cell cultures.
- Analysis of viral RNA (mRNA) and protein expression, including the E2 glycoprotein.
Main Results:
- Wild-type JHMV selectively propagated variants with larger mRNA3 in the rat brain.
- A cloned variant (c1-2) exhibited larger mRNAs 2, 2a, and 3, and a larger E2 glycoprotein compared to wild-type JHMV.
- Selective replication of variants was also observed in neural cell cultures.
- Variants from rat brain and neural cells differed in mRNA 2, 2a, and 65 K protein content.
Conclusions:
- Viruses possessing a larger E2 glycoprotein demonstrate a growth advantage in rat brain cells.
- This selective replication of variants with enhanced growth in neural tissue may contribute to the pathogenesis of acute encephalitis induced by JHMV.