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January 7, 2010Journal of VirologyOpen Access

A Single Amino Acid Substitution in the Capsid of Foot-and-Mouth Disease Virus Can Increase Acid Lability and Confer Resistance to Acid-Dependent Uncoating Inhibition

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Key result

A single amino acid substitution (VP3 A118V) in the FMDV capsid conferred full resistance to inhibitors of endosomal acidification (NH4Cl and concanamycin A) and increased the acid sensitivity of the virion.

Population

BHK-21 cells infected with foot-and-mouth disease virus (FMDV) C-S8c1 and its mutants

Comparison

Amino acid substitutions in the viral capsid vs Parental virus C-S8c1

Design

Preclinical

Authors

MMMiguel A. Martín-AcebesVRVerónica RincónRARosario Armas-Portela

Discussion

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Member takes

Overview

VP3 A118V may drive FMDV resistance to endosomal inhibitors; leaves open effects on natural transmission or vaccine stability.

Structured PICO

P
Population
In vitro study of Foot-and-Mouth Disease Virus (FMDV) mutants in cell cultures (BHK-21, IBRS-2, CHO) to assess resistance to endosomal acidification inhibitors.
I
Intervention
Amino acid substitutions in the viral capsid (VP3 A123T, VP3 A118V, and VP2 D106G)
C
Comparator
Parental virus C-S8c1
O
Outcome
Resistance to NH4Cl and concanamycin A, and acid-induced inactivation of infectivitysurrogate

Specific single amino acid substitutions in the FMDV capsid can modulate acid-induced dissociation and confer resistance to inhibitors of endosomal acidification.

Limitations

  • In vitro study using cell cultures, which may not fully reflect in vivo viral dynamics.

Cite This Study

Martín-Acebes et al. (2010) studied Foot-and-Mouth Disease Virus (FMDV) infection (in vitro). Amino acid substitution VP3 A118V in FMDV capsid vs. Parental FMDV C-S8c1 was evaluated on Resistance to NH4Cl and acid sensitivity (pH50). A single amino acid substitution (VP3 A118V) in the FMDV capsid conferred full resistance to inhibitors of endosomal acidification (NH4Cl and concanamycin A) and increased the acid sensitivity of the virion.

synapsesocial.com/papers/6a6f57e3fe4101aa97dfc189https://doi.org/10.1128/jvi.02311-09
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Viral RNA modulates the acid sensitivity of foot-and-mouth disease virus capsids1995 · 127 citations
  2. 2Evidence for the role of His-142 of protein 1C in the acid-induced disassembly of foot-and-mouth disease virus capsids1999 · 129 citations
  3. 3A single amino acid substitution affects multiple overlapping epitopes in the major antigenic site of foot-and-mouth disease virus of serotype C1990 · 199 citations
  4. 4Complete Alanine Scanning of Intersubunit Interfaces in a Foot-and-Mouth Disease Virus Capsid Reveals Critical Contributions of Many Side Chains to Particle Stability and Viral Function2003 · 55 citations
  5. 5Tissue culture adaptation of foot-and-mouth disease virus selects viruses that bind to heparin and are attenuated in cattle1997 · 299 citations