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September 6, 20181 citationsOpen Access

Characterization of a thermal stable poliovirus mutant reveals distinct mechanisms of virion stabilization

YNYohan N’GuyenPJPalmy JesudhasanEAElizabeth R. Aguilera

Key Result

The VP1-M132V poliovirus mutant exhibited a greater than 1000-fold increase in infectivity after heat treatment compared to wild-type virus, without compromising replication or pathogenesis.

Structured PICO

P
Population
In vitro cell cultures and an in vivo mouse model used to evaluate the thermal stability and pathogenesis of a poliovirus mutant.
I
Intervention
Poliovirus mutant M132V (VP1-M132V)
C
Comparator
Wild-type (WT) poliovirus
O
Outcome
Virion thermal stability (infectivity after heat treatment), viral replication in vitro, and viral shedding and pathogenesis in vivo

A single amino acid mutation (M132V) in the poliovirus VP1 capsid confers significant thermal stability without compromising viral replication or pathogenesis, highlighting distinct mechanisms of environmental virion stabilization.

Main Result

Effect estimate: >1000-fold increased infectivity

Limitations

  • The specific binding sites of bacterial components on viral capsids remain unknown.

Abstract

ABSTRACT Enteric viruses, including poliovirus, are spread by the fecal-oral route. In order to persist and transmit to a new host, enteric virus particles must remain stable once they are in the environment. Environmental stressors such as heat and disinfectants can inactivate virus particles and prevent viral transmission. It has been previously demonstrated that bacteria or bacterial surface glycans can enhance poliovirus virion stability and limit inactivation from heat or bleach. While investigating the mechanisms underlying bacterial-enhanced virion thermal stability, we identified and characterized a poliovirus mutant with increased resistance to heat inactivation. This poliovirus mutant, M132V, harbors a single amino acid change in the VP1 capsid-coding that is sufficient to confer heat resistance. M132V was comparable to wild-type virus for replication in vitro , as well as for replication and pathogenesis in orally-inoculated mice. Although the M132V virus was stable in the absence of bacteria or feces at most temperatures, M132V virus was stabilized by feces at very high temperatures. Additionally, the M132V virus does not have enhanced stability during bleach treatment, suggesting that thermal and bleach inactivation mechanisms are separable. Our results suggest that different mechanisms underlie virion stabilization by bacteria and the M132V mutation. Overall, this work sheds light on factors that influence virion stability. IMPORTANCE Viruses spread by the fecal-oral route need to maintain viability in the environment to ensure transmission. Previous work indicated that bacteria and bacterial surface polysaccharides can stabilize viral particles and enhance transmission. To explore factors that influence viral particle stability, we isolated a mutant poliovirus that is heat resistant. This mutant virus does not require feces for stability at most temperatures, but can be stabilized by feces at very high temperatures. Even though the mutant virus is heat resistant, it is susceptible to inactivation by treatment with bleach. This work provides insight into how viral particles maintain infectivity in the environment.

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Cite This Study

N’Guyen et al. (2018) studied Poliovirus infection. VP1-M132V poliovirus mutant vs. Wild-type poliovirus was evaluated on Viral viability after heat treatment (43°C for 6 hours) (>1000-fold increased infectivity). The VP1-M132V poliovirus mutant exhibited a greater than 1000-fold increase in infectivity after heat treatment compared to wild-type virus, without compromising replication or pathogenesis.

synapsesocial.com/papers/6a746cdbf5fc39414403234ahttps://doi.org/10.1101/410175
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