Genetic Relationship between Cocirculating Human Enteroviruses Species C

Recombination events between human enteroviruses (HEV) are known to occur frequently and to participate in the evolution of these viruses. In a previous study, we reported the isolation of a panel of viruses belonging to the Human enterovirus species C (HEV-C) that had been cocirculating in a small geographic area of Madagascar in 2002. This panel included type 2 vaccine-derived polioviruses (PV) that had caused several cases of acute flaccid paralysis in humans. Previous partial sequencing of the genome of these HEV-C isolates revealed considerable genetic diversity, mostly due to recombination. In the work presented herein, we carried out a more detailed characterization of the genomes of viruses from this collection. First, we determined the full VP1 sequence of 41 of these isolates of different types. These sequences were compared with those of HEV-C isolates obtained from other countries or in other contexts. The sequences of the Madagascan isolates of a given type formed specific clusters clearly differentiated from those formed by other strains of the same type isolated elsewhere. Second, we sequenced the entire genome of 10 viruses representing most of the lineages present in this panel. All but one of the genomes appeared to be mosaic assemblies of different genomic fragments generated by intra- and intertypic recombination. The location of the breakpoints suggested potential preferred genomic regions for recombination. Our results also suggest that recombination between type HEV-99 and other HEV-C may be quite rare. This first exhaustive genomic analysis of a panel of non-PV HEV-C cocirculating in a small human population highlights the high frequency of inter and intra-typic genetic recombination, constituting a widespread mechanism of genetic plasticity and continually shifting the HEV-C biodiversity

Recombination between Polioviruses and Co-Circulating Coxsackie A Viruses: Role in the Emergence of Pathogenic Vaccine-Derived Polioviruses

Ten outbreaks of poliomyelitis caused by pathogenic circulating vaccine-derived polioviruses (cVDPVs) have recently been reported in different regions of the world. Two of these outbreaks occurred in Madagascar. Most cVDPVs were recombinants of mutated poliovaccine strains and other unidentified enteroviruses of species C. We previously reported that a type 2 cVDPV isolated during an outbreak in Madagascar was co-circulating with coxsackieviruses A17 (CA17) and that sequences in the 3′ half of the cVDPV and CA17 genomes were related. The goal of this study was to investigate whether these CA17 isolates can act as recombination partners of poliovirus and subsequently to evaluate the major effects of recombination events on the phenotype of the recombinants. We first cloned the infectious cDNA of a Madagascar CA17 isolate. We then generated recombinant constructs combining the genetic material of this CA17 isolate with that of the type 2 vaccine strain and that of the type 2 cVDPV. Our results showed that poliovirus/CA17 recombinants are viable. The recombinant in which the 3′ half of the vaccine strain genome had been replaced by that of the CA17 genome yielded larger plaques and was less temperature sensitive than its parental strains. The virus in which the 3′ portion of the cVDPV genome was replaced by the 3′ half of the CA17 genome was almost as neurovirulent as the cVDPV in transgenic mice expressing the poliovirus cellular receptor gene. The co-circulation in children and genetic recombination of viruses, differing in their pathogenicity for humans and in certain other biological properties such as receptor usage, can lead to the generation of pathogenic recombinants, thus constituting an interesting model of viral evolution and emergence

Circulation, genetic diversity and evolution of human enteroviruses in Cameroon - interactions with vaccine polioviruses and simian enteroviruses

La diversité génétique des entérovirus (EVs) humains, y compris les poliovirus (PVs), circulant au Cameroun a été évaluée d'une part sur tout le territoire chez des patients atteints de paralysie flasque aiguë, et d'autre part, chez des enfants sains dans la région de l'extrême Nord du pays. Les résultats obtenus indiquent une fréquence élevée couplée à une importante diversité génétique des EVs au Cameroun. Les EVs de l'espèce Human Enterovirus C (HEV-C) représentaient jusqu'à 56,5% des isolats identifiés. En dehors des types viraux mondialement distribués, des types et variants d'EV spécifiquement Africains ont été identifiés. L'étude des échanges génétiques entre HEV-C, incluant les PVs vaccinaux, a confirmé que des recombinaisons fréquentes dans les régions non structurales du génome participent à leur diversité génétique. En particulier les PVs co-circulent et échangent les séquences de leurs régions non structurales avec les autres HEV-C notamment avec les CVA-13, -17 et -20. La co-circulation des PVs et de divers HEV-C pourrait constituer un facteur viral majeur pour l'émergence des PVs recombinants pathogènes dérivés du vaccin (VDPVs). Par ailleurs, des EVs typiquement simiens, mais aussi des EVs précédemment connus comme étant des pathogènes humains ont été identifiés dans les selles de primates non humains (PNH) vivant en captivité et en faune sauvage. En particulier, quatre nouveaux types d'EVs simiens ont été identifiés. Les résultats confirment que la transmission inter-espèces d'au moins certains types d'EV est naturellement possible et pourrait jouer un rôle dans l'émergence de nouveaux EVs de l'homme chez les PNH et vice-versa.The genetic diversity of human enteroviruses (EVs), including polioviruses (PVs), circulating in Cameroon was investigated in acute flaccid paralysis patients throughout the entire territory as well as in healthy children from the far northern region of the country. The results showed a high frequency combined with a high genetic diversity of human EVs in Cameroon. The frequency of EVs belonging to the Human Enterovirus C species (HEV-C) was as high as 56.5% of the identified isolates. Apart from worldwide distributed types, several African specific types and variants were identified. The investigation of genetic exchanges between HEV-C, including vaccine polioviruses, confirmed the fact that frequent recombination in the non structural regions of the genome contribute to their genetic diversity. PVs in particular co-circulate and exchange the sequences of their non structural regions with CVA-13, -17 and -20. The co-circulation of PVs and diverse HEV-C may be a major viral factor for the emergence of pathogenic recombinant vaccine derived PVs (VDPVs). In the other hand, simian specific EVs as well as EVs previously known human EVs were identified in the stools of captive and wild non human primates (NHP). Four novel types of simian EVs in particular were identified. The results confirm that cross-species transmission of at least some EV types can happen naturally and could play a role in the emergence of new EV types from humans to NHP and vice-versa.PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Vaccination antipoliomyélitique et émergence de virus recombinants dérivés de souches vaccinales à Madagascar.

International audienceLettre des orateurs de sessions de communications orales en partenaria

Molecular aspects of poliovirus biology with a special focus on the interactions with nerve cells.

Poliovirus (PV), the pathogenic agent of paralytic poliomyelitis, is the prototype of the picornavirus family. Although paralytic poliomyelitis has been nearly totally eradicated in most industrialized countries, PV continues to be an important public health problem in many developing countries. Moreover, in industrialized countries, two current concerns are the occurrence, albeit at a very low frequency, of vaccine-associated paralytic poliomyelitis, due to the genetic instability of the attenuated oral PV strains in vaccines, and the emergence of a neuro-muscular pathology in many survivors of the acute disease, called the post-polio syndrome. PV has been targeted by the World Health Organization for world-wide eradication in the coming decade and continues to be the subject of intensive research. The advances made in the molecular biology of PV, taken together with the development of new animal and cell models, have permitted a new look at a key step in the pathogenesis of poliomyelitis, i.e. the interactions between PV and nerve cells. These aspects of PV biology are developed in this review according to three themes: (i) the PV host range; (ii) the molecular determinants of PV neurovirulence and attenuation; and (iii) the persistence of PV in nerve cells, which has proven to be an interesting new domain in the field of PV research