The Golgi protein ACBD3, an interactor for poliovirus protein 3A, modulates poliovirus replication.
We have shown that the circulating vaccine-derived polioviruses responsible for poliomyelitis outbreaks in Madagascar have recombinant genomes composed of sequences encoding capsid proteins derived from poliovaccine Sabin, mostly type 2 (PVS2), and sequences encoding nonstructural proteins derived from other human enteroviruses. Interestingly, almost all of these recombinant genomes encode a nonstructural 3A protein related to that of field coxsackievirus A17 (CV-A17) strains. Here, we investigated the repercussions of this exchange, by assessing the role of the 3A proteins of PVS2 and CV-A17 and their putative cellular partners in viral replication. We found that the Golgi protein acyl-coenzyme A binding domain-containing 3 (ACBD3), recently identified as an interactor for the 3A proteins of several picornaviruses, interacts with the 3A proteins of PVS2 and CV-A17 at viral RNA replication sites, in human neuroblastoma cells infected with either PVS2 or a PVS2 recombinant encoding a 3A protein from CV-A17 [PVS2-3A(CV-A17)]. The small interfering RNA-mediated downregulation of ACBD3 significantly increased the growth of both viruses, suggesting that ACBD3 slowed viral replication. This was confirmed with replicons. Furthermore, PVS2-3A(CV-A17) was more resistant to the replication-inhibiting effect of ACBD3 than the PVS2 strain, and the amino acid in position 12 of 3A was involved in modulating the sensitivity of viral replication to ACBD3. Overall, our results indicate that exchanges of nonstructural proteins can modify the relationships between enterovirus recombinants and cellular interactors and may thus be one of the factors favoring their emergence.
Institut Pasteur, Unité de Biologie des Virus Entériques, Paris, France.
François
F
Téoulé
Cynthia
C
Brisac
Isabelle
I
Pelletier
Pierre-Olivier
PO
Vidalain
Sophie
S
Jégouic
Carmen
C
Mirabelli
Maël
M
Bessaud
Nicolas
N
Combelas
Arnaud
A
Autret
Frédéric
F
Tangy
Francis
F
Delpeyroux
Bruno
B
Blondel
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009474:Neurons / Q000821:virology; D017955:Poliovirus / Q000502:physiology*; D014758:Viral Core Proteins / Q000378:metabolism*; D014779:Virus Replication
C109349:3A protein, Poliovirus; C449459:ACBD3 protein, human; D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D014758:Viral Core Proteins