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

Echovirus infection causes rapid loss-of-function and cell death in human dendritic cells.

Contains fulltext : 51866.pdf (publisher's version ) (Closed access)Coxsackie B viruses (CVB) and Echoviruses (EV) form a single species; Human enterovirus B (HeV-B), within the genus Enterovirus. Although HeV-B infections are usually mild or asymptomatic, they can cause serious acute illnesses. In addition, HeV-B infections have been associated with chronic immune disorders, such as type 1 diabetes mellitus and chronic myocarditis/dilated cardiomyopathy. It has therefore been suggested that these viruses may trigger an autoimmune process. Here, we demonstrate that human dendritic cells (DCs), which play an essential role in orchestration of the immune response, are productively infected by EV, but not CVB strains, in vitro. Infection does not result in DC activation or the induction of antiviral immune responses. Instead, EV infection rapidly impedes Toll-like receptor-mediated production of cytokines and upregulation of maturation markers, and ultimately causes loss of DC viability. These results describe for the first time the effect of EV on the function and viability of human DCs and suggest that infection of DCs in vivo can impede regulation of immune responses

Evidence for emergence of diverse polioviruses from C-cluster coxsackie A viruses and implications for global poliovirus eradication

The poliovirus (PV) eradication campaign is conducted on the premise that this virus, because of the lack of a zoonotic reservoir, will not reemerge once eradicated. This report examines the origin of PV using theoretical and experimental approaches. Our rooted phylogenetic analysis suggests a speciation of PV from a C-cluster coxsackie A virus (C-CAV) ancestor through mutation of the capsid that caused a receptor switch from intercellular adhesion molecule-1 to CD155, leading to a change of pathogenicity. This hypothesis is supported experimentally with chimeras generated from three different pairs of PV and C-CAV. Those carrying the PV capsid and the replication proteins of C-CAVs replicated well, whereas their reciprocal counterparts were either debilitated or dead. This phenomenon of asymmetry is observed also in recombinants between PV1 and C-CAV20, selected in tissue culture cells using a previously undescribed protocol. The recombinants are generated at frequencies of 10−6 typical for PV interserotype recombination. Strikingly, they resemble genetically and phenotypically, including neurovirulence in CD155 transgenic mice, the large majority of circulating vaccine-derived PVs that have caused poliomyelitis outbreaks in different parts of the world. These data provide experimental evidence for C-CAVs being partners to PVs in generating diverse PV progeny by homologous recombination. They support speciation of a novel human pathogen (PV) from a pool of different human pathogens (C-CAVs). In a PV-free world without PV neutralizing antibodies, contemporary C-CAV, like their ancestor(s), could be fertile ground for a PV-like agent to emerge by mutation