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Two determinants in the capsid of a persistent type 3 poliovirus exert different effects on mutant virus uncoating
Gillian Duncan1, Florence Colbère-Garapin1
1Unité de Neurovirologie et R égén ération du Système Nerveux, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France1.
Abstract:
Mutant polioviruses (PV) have been previously found to be capable of establishing persistent infections in HEp-2c cells. Together, two amino acid substitutions in the viral capsid of a type 3 poliovirus (PV-3), at positions VP213 and VP1(290), are sufficient to confer the persistent phenotype to a normally lytic virus. When susceptible cells are infected, the double mutant T7L+2L(13)1N(290) undergoes unique conformational changes in the capsid, modifying its sedimentation coefficient from 160S to 147S. In the present study, we have further investigated mutant PV decapsidation and, in particular, the effect of each determinant independently. Our results indicate that the novel 147S form was also generated by a mutant carrying only the determinant 1N290. This form was not produced as a result of inherent capsid instability and it was generated only upon specific PV-host cell interactions. The second viral determinant, 2L13, also modified receptor-induced conformational changes, although differently from 1N290.
Insights
Mutant polioviruses (PV) can cause persistent infections. A single mutation (1N290) in the PV-3 capsid can induce unique conformational changes, leading to a 147S form upon host cell interaction, contributing to viral persistence.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Mutant polioviruses (PV) are known to establish persistent infections in HEp-2c cells.
- Two specific amino acid substitutions (VP213 and VP1(290)) in the type 3 poliovirus (PV-3) capsid confer a persistent phenotype to an otherwise lytic virus.
Purpose of the Study:
- To investigate poliovirus (PV) decapsidation mechanisms.
- To determine the independent effects of two specific viral capsid determinants (VP213 and VP1(290)) on viral persistence and capsid conformation.
Main Methods:
- Analysis of mutant poliovirus (PV) decapsidation.
- Investigation of capsid conformational changes using sedimentation coefficient analysis.
- Assessment of individual determinant effects (1N290 and 2L13) on PV-host cell interactions.
Main Results:
- A double mutant (T7L+2L(13)1N(290)) exhibits unique capsid conformational changes, altering its sedimentation coefficient from 160S to 147S upon infection.
- The 147S form is also generated by a mutant with only the 1N290 determinant, indicating its role in this conformational change.
- The 147S form is not due to inherent capsid instability but arises from specific PV-host cell interactions.
- The 2L13 determinant also influences receptor-induced conformational changes, but distinct from the 1N290 effect.
Conclusions:
- The 1N290 mutation is a key determinant for inducing the 147S capsid conformation in poliovirus (PV).
- This specific conformational change is dependent on PV-host cell interactions, not intrinsic capsid instability.
- Understanding these mutations and their effects on capsid conformation provides insights into the mechanisms of poliovirus (PV) persistence.