CMLS, Cell. Mol. Life Sci. 54 (1998) 1385–14021420-682X:98:121385-18 1.500.20:0Verlag, Basel, 1998
Molecular mechanisms of poliovirus persistence: key role of
capsid determinants during the establishment phase.
I. Pelletier, G. Duncan, N. Pavio and F. Colbe`re-Garapin*
Groupe de Ge´ne´tique Virale, Unite´ de Neurovirologie et Re´ge´ne´ration du Syste`me Nerveux, Institut Pasteur,
25 rue du Dr. Roux, F-75724 Paris Cedex 15 (France), Fax 33 1 45 68 87 80, e-mail: firstname.lastname@example.org
Received 2 June 1998; received after revision 28 July 1998; accepted 28 July 1998
Abstract. As viral persistence is of major medical im- strains can be used to study the PV-HEp-2 cell interportance.
Well-characterized, simple models are needed actions. The viral determinants of persistence have to improve our understanding of persistent infections. been investigated with this model, and PV determi .We have chosen to study the molecular mechanisms nants have proven to be of crucial importance for the of viral persistence with the poliovirus (PV), because establishment of persistence in HEp-2 cells. Precise dethis picornavirus is one of the best characterized ani- terminants of PV persistence have been identified for mal viruses, it infects the central nervous system PV serotypes 1 and 3, in capsid proteins VP1 andwhich is a target organ for viral persistence, and it VP2. These determinants modify the early steps of thebelongs to the Picorna6iridae family of viruses, which PV cycle, and in particular, the conformational modincludes several naturally persisting viruses. We have ifications of the capsid following virus adsorption developed models of PV persistence in neuronal and onto its receptor. These results permit us to propose epidermoid cells, and the present review will focus on several hypotheses concerning PV persistence and the latter one because both lytic and persistent PV early steps of the PV cycle.
Viral persistence is of major medical importance.
Many viruses are able to establish long-lasting, persistent Infections in their host, and some of them are even responsible for severe pathologies . Retroviruses, and most DNA viruses including in particular herpesviruses,are known to establish persistent infections in their hosts. The acquired immunodeficiency syndrome results from the persistence of the human immunodeficiency virus , which, in turn, favours the reactivation of many other persistent viruses, with the appearance of the corresponding pathologies. Several non retrovirus RNA viruses also persist in their hosts . For example, a common childhood infection caused by the measles virus can lead to a very rare but fatal pathology, subacute sclerosing panencephalitis, after a decade of persistent viral infection in the central nervous system (CNS). Another example is provided by the hepatitis C virus, which persists in humans very frequently after the primary infection, inducing chronic hepatitis which may finally provoke a hepatocarcinoma .
Moreover, several chronic pathologies are probably triggered by viral persistence. It has been
proposed that a persistent coxsackievirus infection could be involved in cases of chronic heart disease and
in diabetes mellitus [5, 6]. Indeed, during viral persistence,housekeeping functions of the cell may not be
altered, whereas specialized functions, like the secretion of insulin, may be affected, resulting in pathology
at the level of the organism [7–9]. Other viruses, in particular retro-, corona- and herpesviruses, are proposed
to play a role in the development of autoimmune diseases such as multiple sclerosis [10–13].
These few examples provide evidence that viral persistence is of major medical importance. Thus, 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 CNS, which is a target organ for viral persistence
; and it belongs to a family of viruses that include several naturally persisting viruses. Furthermore, in a
certain number of patients with a history of paralytic poliomyelitis, a second pathology, possibly resulting
from viral persistence, has been observed to develop several decades after the acute disease [14, 15]. It is
Therefore interesting to investigate the capacity of PV to establish persistent infections in human cells.
General mechanisms underlying viral persistence
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