Enterovirus C strains circulating in Nigeria and their contribution to the emergence of recombinant circulating vaccine-derived polioviruses

Abstract

Between 2005 and 2011, 23 lineages of circulating vaccine-derived polioviruses (cVDPVs) were detected in Nigeria with nonstructural region (NSR) of non-polio enterovirus C (NPEV-C) origin. However, no information exists on NPEV-C strains recombining with oral poliovirus type 2 vaccine strains (OPV2) to make type 2 cVDPVs (cVDPV2s) in Nigeria. This study was therefore designed to investigate the probable contribution of NPEV-Cs recently isolated in the region to the emergence of cVDPV2s. Eleven enterovirus C (EV-C) strains (8 NPEV-Cs and 3 PV2s) previously isolated by the authors were analysed in this study. All 11 isolates were assayed for cell-line-dependent growth restriction in four cell lines (LLC-MK2, MCF-7, RD and L20B). Subsequently, the isolates were subjected to RT-PCR specific for VP1 and 3Dpol/3'-UTR of EV-C. All PCR products were sequenced, and phylogenetic analysis was performed. All eight NPEV-Cs replicated exclusively in the MCF-7 cell line, while the three PV2s replicated in all four cell lines. The eight NPEV-Cs were identified as CVA13 (7 isolates) and CVA20 (1 isolate) by VP1 analysis, while all 11 isolates were confirmed to be EV-Cs by 3Dpol/3'-UTR analysis. In addition, phylogeny violations suggested that some cVDPVs might have recombined with common ancestors of the NPEV-Cs described in this study. This was confirmed by the scatter plot of divergence in VP1 against that of 3Dpol/3'-UTR sequences for pairs of isolates. The results of this study showed that the NSR of unknown origin found in cVDPVs from the region might have come from NPEV-Cs (e.g., CVA13 and CVA20) circulating in Nigeria.

The Impact of a Panenterovirus Vp1 Assay on Our Perception of the Enterovirus Diversity Landscape of a Sample

“…Though the strategy suggested above might lengthen the storage time of enterovirus isolates recovered and our ability to revisit such isolates for re-analysis, prior subjection to cell culture might result in cell line bias and consequently, influence our perception of the enterovirus diversity landscape of the sample as previously shown [17][18][19][20][21][22]. Subsequent to the completion of this study, we used the same algorithm described in this study to directly screen faecal suspensions from AFP cases and their corresponding isolates on RD cell line.…”

Vaccination via Chloroplast Genetics: Affordable Protein Drugs for the Prevention and Treatment of Inherited or Infectious Human Diseases

“…In particular, animals fed with plant material containing ~0.05 mg of CTB-ACE2 showed 40% more ACE2 activity in serum and 20% more ACE2 activity in retinas than mice given wild-type material (119). More importantly, mice fed with plant cells containing ~0.25 mg of CTB-Ang-(1–7) or 0.05 mg of CTB-ACE2 showed reduced symptoms of both induced and autoimmune ocular inflammation, demonstrating the efficacy of this system to treat retinopathy (Figure 2 d ) (119). …”

“…A good therapeutic target to treat retinal inflammation is the renin-angiotensin system (RAS) (41). The RAS consists of two axes with opposing effects: the proinflammatory ACE/AngII/AT 1 axis and the anti-inflammatory/vasoprotective ACE2/Ang-(1–7)/Mas axis (110). To treat ocular inflammation, two components of the anti-inflammatory axis, ACE2 and Ang-(1–7), were separately fused with CTB and introduced into the tobacco plastid genome.…”

“…The RAS consists of two axes with opposing effects: the proinflammatory ACE/AngII/AT 1 axis and the anti-inflammatory/vasoprotective ACE2/Ang-(1–7)/Mas axis (110). To treat ocular inflammation, two components of the anti-inflammatory axis, ACE2 and Ang-(1–7), were separately fused with CTB and introduced into the tobacco plastid genome. Proteins encoded by both constructs interacted with GM1 in vitro, and up to 5 h after oral delivery, they were detected in sera and retinas of treated mice, confirming their ability to cross the BRB (119).…”

“…To that end, a novel treatment targeting the RAS is currently being developed. Feeding mice with plant cells containing 0.05 mg of CTB-ACE2 or 0.5 mg of CTB-Ang-(1–7) led to a 37% or twofold increase of these respective proteins in circulation and protected rats from chemically induced PH (117). Oral delivery of CTB-ACE2 or CTB-Ang-(1–7) could halt or reverse the progression of PH, improve right heart function, and decrease pulmonary wall thickness and lung injury (Figure 2 e ) (117).…”