Evolution of echovirus 11 in a chronically infected immunodeficient patient.

Deep sequencing was used to determine complete nucleotide sequences of echovirus 11 (EV11) strains isolated from a chronically infected patient with CVID as well as from cases of acute enterovirus infection. Phylogenetic analysis showed that EV11 strains that circulated in Israel in 1980-90s could be divided into four clades. EV11 strains isolated from a chronically infected individual belonged to one of the four clades and over a period of 4 years accumulated mutations at a relatively constant rate. Extrapolation of mutations accumulation curve into the past suggested that the individual was infected with circulating EV11 in the first half of 1990s. Genomic regions coding for individual viral proteins did not appear to be under strong selective pressure except for protease 3C that was remarkably conserved. This may suggest its important role in maintaining persistent infection

Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry

Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72%) cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4) and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed

Evolution of echovirus 11 in a chronically infected immunodeficient patient

<div><p>Deep sequencing was used to determine complete nucleotide sequences of echovirus 11 (EV11) strains isolated from a chronically infected patient with CVID as well as from cases of acute enterovirus infection. Phylogenetic analysis showed that EV11 strains that circulated in Israel in 1980-90s could be divided into four clades. EV11 strains isolated from a chronically infected individual belonged to one of the four clades and over a period of 4 years accumulated mutations at a relatively constant rate. Extrapolation of mutations accumulation curve into the past suggested that the individual was infected with circulating EV11 in the first half of 1990s. Genomic regions coding for individual viral proteins did not appear to be under strong selective pressure except for protease 3C that was remarkably conserved. This may suggest its important role in maintaining persistent infection.</p></div

Monitoring of Enterovirus D68 Outbreak in Israel by a Parallel Clinical and Wastewater Based Surveillance

Enterovirus D68 (EVD68) was recently identified as an important cause of respiratory illness and acute flaccid myelitis (AFM), mostly in children. Here, we examined 472 pediatric patients diagnosed with severe respiratory illness and screened for EVD68 between April and October 2021. In parallel, samples collected from a wastewater treatment plant (WWTP) covering the residential area of the hospitalized patients were also tested for EVD68. Of the 472 clinical samples evaluated, 33 (7%) patients were positive for EVD68 RNA. All wastewater samples were positive for EVD68, with varying viral genome copy loads. Calculated EVD68 genome copies increased from the end of May until July 2021 and dramatically decreased at the beginning of August. A similar trend was observed in both clinical and wastewater samples during the period tested. Sequence analysis of EVD68-positive samples indicated that all samples originated from the same branch of subclade B3. This study is the first to use wastewater-based epidemiology (WBE) to monitor EVD68 dynamics by quantitative detection and shows a clear correlation with clinically diagnosed cases. These findings highlight the potential of WBE as an important tool for continuous surveillance of EVD68 and other enteroviruses

Gradual accumulation of mutations in iEV11 illustrated by neighbor-joining tree (A) and plots of the number of nucleotide and amino acid substitutions vs. time of isolation (B).

<p>The analysis was performed for the entire genome of these strains relative to the closest cEV11 isolate. Phylogenetic tree was constructed with neighbor-joining method and bootstrap values (N = 1000) are shown near the internal nodes of the tree.</p

Predicted secondary structures of Z-domain in the 3'-UTR for HEV-B and Coxsackie B3 [24] and iEV11-5789 determined in this paper.

<p>The Israeli sequences were superimposed on the three-dimensional folding model for the human enterovirus Z domain in the 3’UTR taken from Merkel et. al. [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006943#ppat.1006943.ref024" target="_blank">24</a>].</p

Phylogenetic trees constructed based on P1, P2, and P3 regions of EV11 genomes determined in this study along with reference HEV-B sequences.

<p>The trees were constructed using neighbor-joining method of Saitou and Nei [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006943#ppat.1006943.ref046" target="_blank">46</a>].</p

Phylogenetic relationship between full-length sequences of EV11 strains isolated in Israel in 1992–1999.

<p>iEV11 strains belonging to genogroup A are shown in red, cEV11 of genogroup A are shown in orange, while genogroups B, C, D in purple, blue, and green, respectively. The tree was constructed using unweighted pair group method with arithmetic mean (UPGMA). Bootstrap values (N = 1000) are indicated near the internal nodes of the tree.</p

Predicted secondary structure of domain V of EV11 IRES element.

<p>Two best models are presented on panels A and B. Three-dimensional folding models of Loop V of the internal ribosomal entry site (IRES) in the 5’UTR were prepared using the web-based Unified Nucleic Acid Folding and hybridizing Package [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006943#ppat.1006943.ref017" target="_blank">17</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006943#ppat.1006943.ref018" target="_blank">18</a>] at the University of Albany NY, USA, (<a href="http://mfold.rna.albany.edu" target="_blank">http://mfold.rna.albany.edu</a>; last accessed November 2014) and the consensus sequence for the Israeli isolates.</p

Amino acid and nucleotide substitutions densities (Da and Dn respectively) for individual parts of EV11 genome for iEV11 (A) and cEV11 (B).

<p>Error bars show the 95% confidence limits for binomial proportions.</p