title: Modulation of foot-and-mouth disease virus pH threshold for uncoating correlates with differential sensitivity to inhibition of cellular Rab GTPases and decreases infectivity in vivo.
abstract: The role of cellular Rab GTPases that govern traffic between different endosome populations was analysed on foot-and-mouth disease virus (FMDV) infection. Changes of viral receptor specificity did not alter Rab5 requirement for infection. However, a correlation between uncoating pH and requirement of Rab5 for infection was observed. A mutant FMDV with less acidic uncoating pH threshold was less sensitive to inhibition of Rab5, whereas another mutant with more acidic requirements was more sensitive to inhibition of Rab5. On the contrary, opposed correlations between uncoating pH and dependence of Rab function were observed upon expression of dominant-negative forms of Rab7 or 11. Modulation of uncoating pH also reduced FMDV virulence in suckling mice. These results are consistent with FMDV uncoating inside early endosomes and indicate that displacements from optimum pH for uncoating reduce viral fitness in vivo.
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' (UAM/CSIC), Cantoblanco, Madrid, Spain.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Vázquez-Calvo
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' (UAM/CSIC), Cantoblanco, Madrid, Spain.
authors.forename: Flavia
authors.initials: F
authors.lastname: Caridi
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' (UAM/CSIC), Cantoblanco, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Rodriguez-Pulido
authors.affiliation: Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Borrego
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' (UAM/CSIC), Cantoblanco, Madrid, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Sáiz
authors.affiliation: Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, Madrid, Spain.|Centro de Biología Molecular 'Severo Ochoa' (UAM/CSIC), Cantoblanco, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sobrino
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' (UAM/CSIC), Cantoblanco, Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martín-Acebes
mesh_terms: D000818:Animals; D002021:Buffers; D002460:Cell Line; D006224:Cricetinae; D011992:Endosomes; D029544:Foot-and-Mouth Disease Virus / Q000502:physiology*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D006863:Hydrogen-Ion Concentration; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000502:physiology*; D053586:Virus Internalization; D020696:rab5 GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D002021:Buffers; D011991:Receptors, Virus; D049452:Green Fluorescent Proteins; D020696:rab5 GTP-Binding Proteins