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Persistent poliovirus infection: establishment and maintenance involve distinct mechanisms
S Borzakian1, T Couderc, Y Barbier
1Unité de Virologie Médicale, Institut Pasteur, Paris, France.
Abstract:
Mutants of poliovirus (PV) with highly modified biological properties can be selected in vitro in cells of neural origin. Mutations accumulate in the genome of type 1 PV strains selected in human neuroblastoma cells, modifying cell specificity and conferring to the virus the ability to persist in such nonneural cells as HEp-2c (Pelletier et al., Virology 180, 729 1991). With this cell system, we have both parent lytic strains and persistent PV mutants; these were used to study the mechanisms of the establishment and maintenance of the persistent infection. We found that a persistent infection was established when the lytic potential of the virus was reduced; this involved both an early and a late event of the virus cycle for the type 1 mutants. In contrast, maintenance of the infection did not correlate with the reduced lytic potential of the viruses, but rather with the selection of mutant cell populations of various phenotypes. Two cell lines, representative of two phenotypes, were studied in greater detail. In the first one, HEp-S32 (cl7), the PV receptor was not detected by cytofluorometry and viral genomes were detected by in situ hybridization in 2% of the cells. In the second cell line, HEp-S31 (cl18), 97% of the cells expressed the PV receptor, viral genomes were detected in 9-10% of the cells, and viral antigens in 5-10% of the cells. With this cell line, the cure of the culture or, alternatively, the lysis of the majority of cells, could be induced under specific culture conditions. We propose a model involving an equilibrium between an abortive and a lytic infection to explain the properties of cells persistently infected with PV.
Insights
Researchers studied poliovirus (PV) mutants in neural cells, finding that reduced viral lytic potential establishes persistent infections. However, infection maintenance depends on selected cell populations, not viral properties.
Area of Science:
- Virology
- Cell Biology
- Infectious Diseases
Background:
- Poliovirus (PV) mutants with altered biological properties can be selected in vitro using neural cells.
- Type 1 PV strains selected in human neuroblastoma cells accumulate mutations, changing cell specificity and enabling persistence in non-neural cells like HEp-2c.
Purpose of the Study:
- To investigate the mechanisms behind the establishment and maintenance of persistent poliovirus infections using parent lytic strains and persistent PV mutants.
- To understand the role of viral lytic potential and host cell selection in persistent viral infections.
Main Methods:
- Selection of poliovirus mutants in vitro using neural and non-neural cell lines (HEp-2c).
- Analysis of viral genome and antigen presence in infected cells using in situ hybridization and cytofluorometry.
- Characterization of two distinct cell phenotypes (HEp-S32 and HEp-S31) exhibiting persistent poliovirus infection.
Main Results:
- Persistent infection establishment requires reduced viral lytic potential, affecting early and late stages of the virus cycle.
- Infection maintenance is linked to the selection of host cell populations with varying phenotypes, not solely to reduced viral lytic potential.
- Two cell lines showed distinct characteristics: HEp-S32 lacked PV receptors, while HEp-S31 expressed receptors and supported viral genome/antigen presence, allowing for culture cure or lysis under specific conditions.
Conclusions:
- A model involving an equilibrium between abortive and lytic infections is proposed to explain persistent poliovirus infection in host cells.
- The study highlights the complex interplay between viral mutations and host cell selection in establishing and maintaining persistent viral infections.