Molecular mechanisms of poliovirus persistence: key role of capsid determinants during the establishment phase

Abstract

As viral persistence is of major medical importance, well-characterized, simple models are needed to improve our understanding of persistent infections. We have chosen to study the molecular mechanisms of viral persistence with the poliovirus (PV), because this picornavirus is one of the best characterized animal viruses, it infects the central nervous system which is a target organ for viral persistence, and it belongs to the Picornaviridae family of viruses, which includes several naturally persisting viruses. We have developed models of PV persistence in neuronal and epidermoid cells, and the present review will focus on the latter one because both lytic and persistent PV strains can be used to study the PV-HEp-2 cell interactions. The viral determinants of persistence have been investigated with this model, and PV determinants have proven to be of crucial importance for the establishment of persistence in HEp-2 cells. Precise determinants of PV persistence have been identified for PV serotypes 1 and 3, in capsid proteins VP1 and VP2. These determinants modify the early steps of the PV cycle, and in particular, the conformational modifications of the capsid following virus adsorption onto its receptor. These results permit us to propose several hypotheses concerning PV persistence and the early steps of the PV cycle.

Virus-Host Coevolution in a Persistently Coxsackievirus B3-Infected Cardiomyocyte Cell Line

“…In a steady-state infection, all cells are infected, both virus and cell multiplication proceed without the cell being killed, and the cell culture continuously releases virus (21,39). However, intermediate models also exist (51). HL-1 CVB3 cells showed the typical signs of persistent carrier-state infection with high virus titers.…”

“…In vitro cell systems with carrier-state virus infections have been shown to provide a useful approach for identifying factors regulating viral persistence (23,51). To investigate mechanisms of CVB3 persistence in cardiac cells, a CVB3 carrierstate infection of primary human myocardial fibroblasts (HMF) was established several years ago (27,28).…”

Establishment of persistent infection with foot-and-mouth disease virus in BHK-21 cells

“…The results explained exactly why the persistence of FMDV O (Akesu/58/2002) was not established merely by growth of BHK-21 cells survived. The effect of the multiplicity of infection on the establishment of persistent infections with poliovirus in Hep-2 cell cultures had been previously shown that low multiplicity of infection favored establishment of persistent infection [29]. Based on these results, a very low multiplicity of 0.01 PFU/cell was used for infection to establish FMDV persistence in the assay.…”

Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection

“…Signs of late apoptotic responses detectable after the phase of active virus growth and the development of CPE (Romanova et al, 2005) in RD cells allowed us to probe into the apoptosis-evading mechanism during productive infection. Pelletier et al (1998) that the multiplicity of infection (moi) also plays an important role in the outcome of infection. A lower moi can leave the infected cell sufficient time to produce certain factors necessary for its survival.…”