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A determinant for central nervous system persistence localized in the capsid of Theiler's murine encephalomyelitis
C Adami1, A E Pritchard, T Knauf
1Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, and Evanston Hospital, Illinois 60201, USA.
Abstract:
The demyelinating process in Theiler's murine encephalomyelitis virus (TMEV) infection in mice requires virus persistence in the central nervous system. Using recombinant TMEV assembled between the virulent GDVII and less virulent BeAn virus cDNAs, we now provide additional evidence supporting the localization of a persistence determinant to the leader P1 (capsid) sequences. Further, recombinant viruses in which BeAn sequences progressively replaced those of GDVII within the capsid starting at the leader NH2 terminus suggest that a conformational determinant requiring homologous sequences in both the VP2 puff and VP1 loop regions, which are in close contact on the virion surface, might underlie persistence.
Insights
Theiler
Area of Science:
- Neurovirology
- Viral Pathogenesis
- Central Nervous System Infections
Background:
- Theiler's murine encephalomyelitis virus (TMEV) infection causes demyelination in mice.
- Virus persistence in the central nervous system (CNS) is crucial for TMEV-induced demyelination.
Purpose of the Study:
- To investigate the role of viral capsid sequences in TMEV persistence.
- To identify specific regions within the TMEV capsid responsible for maintaining infection in the CNS.
Main Methods:
- Construction and characterization of recombinant TMEV strains.
- Utilizing a combination of virulent (GDVII) and less virulent (BeAn) TMEV cDNA sequences.
- Systematic replacement of viral capsid sequences to map determinants of persistence.
Main Results:
- Evidence supports the localization of a TMEV persistence determinant to the leader P1 (capsid) sequences.
- Progressive replacement of GDVII sequences with BeAn sequences within the capsid identified specific regions involved in persistence.
- A conformational determinant involving homologous sequences in VP2 puff and VP1 loop regions may underlie TMEV persistence.
Conclusions:
- The P1 capsid sequences play a critical role in TMEV persistence within the CNS.
- Specific structural features within the TMEV capsid, particularly involving VP2 and VP1, are essential for establishing and maintaining chronic infection and subsequent demyelination.