Persistence of the poliovirus genome in the cerebrospinal fluid of patients affected by post-polio syndrome
Abstract number: 1733_1027
Baj A., Monaco S., Zanusso G., Molteni F., Toniolo A.
Objectives: Polioviruses (PV; three types) are small, non-enveloped, positive-strand RNA viruses belonging to the Enterovirus genus of Picornaviridae. Twenty to thirty years after being hit by paralytic poliomyelitis, over 50% of patients develop the so called ``post-polio syndrome'' (PPS). PPS is characterised by slowly progressing muscular weakness, chronic pain, fatigue, and other symptoms. The cause of PPS is likely due to distal degeneration of enlarged post-poliomyelitis motor units. Virus persistence in the central nervous system (CNS) has long been investigated with controversial results.
Methods: PPS patients aged 5065 years have been investigated. The PV genome has been searched for in cerebrospinal fluid (CSF) samples using RT-PCR with primers directed to different genomic regions. The utilised amplification methods were capable of detecting <10 genome equivalents per reaction tube. Direct sequencing of purified amplicons allowed identifying the persisting PV serotype. CSF samples from patients with non-infectious pathologies were used as controls.
Results: All investigated patients (11/11) were positive for the presence of PV genomic fragments. The 5' untranslated sequence represented the most sensitive target for molecular detection. Sequencing of VP1 and 2A tracts revealed that the PV type-1 genome was present in most patients. Infectious virus was isolated in cell culture from a single patient undergoing orthopaedic surgery. Complete sequencing of the isolate is expected to shed light on molecular mechanisms of PV persistence. No PV amplicons were detected in CSF samples from control patients.
Conclusion: By gene amplification and genome sequencing, we have shown that PV genomes are able to persist for long periods of time (i.e., >30 years) in the CNS of PPS patients. Though the contribution of viral persistence to PPS pathogenesis is still undefined, our findings may contribute to introducing new molecular tools for PPS diagnosis. The finding of persistent PVs also indicates the need of exploring innovative therapeutic methods for PPS patients. PPS, in fact, represents the most prevalent motor neuron disease today.
Support from Cariplo Foundation, Varese and Milano (Italy) is gratefully acknowledged.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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