World-Wide Prevalence and Genotype Distribution of Enteroviruses

Many pathogenic viruses are endemic among human populations and can cause a broad variety of diseases, some potentially leading to devastating pandemics. How virus populations maintain diversity and what selective pressures drive population turnover, is not thoroughly understood. We conducted a large-scale phylodynamic analysis of 27 human pathogenic RNA viruses spanning diverse life history traits in search of unifying trends that shape virus evolution. For most virus species, we identify multiple, co-circulating lineages with low turnover rates. These lineages appear to be largely noncompeting and likely occupy semi-independent epidemiological niches that are not regionally or seasonally defined. Typically, intra-lineage mutational signatures are similar to inter-lineage signatures. The principal exception are members of the family Picornaviridae, for which mutations in capsid protein genes are primarily lineage-defining. The persistence of virus lineages appears to stem from limited outbreaks within small communities so that only a minor fraction of the global susceptible population is infected at any time. As disparate communities become increasingly connected through globalization, interaction and competition between lineages might increase as well, which could result in changing selective pressures and increased diversification and/or pathogenicity. Thus, in addition to zoonotic events, ongoing surveillance of familiar, endemic viruses appears to merit global attention with respect to the prevention or mitigation of future pandemics.SignificanceNumerous pathogenic viruses are endemic in humans and cause a broad variety of diseases, but what is their potential of causing new pandemics? We show that most human pathogenic RNA viruses form multiple, co-circulating lineages with low turnover rates. These lineages appear to be largely noncompeting and occupy distinct epidemiological niches that are not regionally or seasonally defined, and their persistence appears to stem from limited outbreaks in small communities so that a minor fraction of the global susceptible population is infected at any time. However, due to globalization, interaction and competition between lineages might increase, potentially leading to increased diversification and pathogenicity. Thus, endemic viruses appear to merit global attention with respect to the prevention of future pandemics.

We used wastewater-based epidemiology and amplicon-based long-read high-throughput sequencing for surveillance of enteroviruses (EVs) in Maricopa County, Arizona, Southwest United States. We collected 48 samples from 13 sites in three municipalities between 18 June and 1 October 2020, and filtered (175 mL each; 0.45 µm pore size) and extracted RNA from the filter-trapped solids. The RNA was converted to cDNA and processed through two workflows (Sanger sequencing (SSW) and long-read Illumina sequencing (LRISW)) each including a nested polymerase chain reaction (nPCR) assay. We subjected the ~350 bp amplicon from SSW to Sanger sequencing and the ~1900–2400 bp amplicon from LRISW to Illumina sequencing. We identified EV contigs from 11 of the 13 sites and 41.67% (20/48) of screened samples. Using the LRISW, we detected nine EV genotypes from three species (Enterovirus A (CVA4, EV-A76, EV-A90), Enterovirus B (E14) and Enterovirus C (CVA1, CVA11, CVA13, CVA19 and CVA24)) with Enterovirus C representing approximately 90% of the variants. However, the SSW only detected the five Enterovirus C types. Similarity and phylogenetic analysis showed that multiple Enterovirus C lineages were circulating, co-infecting and recombining in the population during the season despite the SARS-CoV-2 pandemic and the non-pharmaceutical public health measures taken to curb transmission.

Significance Numerous pathogenic viruses are endemic in humans and cause a broad variety of diseases, but what is their potential for causing new pandemics? We show that most human pathogenic RNA viruses form multiple, cocirculating lineages with low turnover rates. These lineages appear to be largely noncompeting and occupy distinct epidemiological niches that are not regionally or seasonally defined, and their persistence appears to stem from limited outbreaks in small communities so that only a small fraction of the global susceptible population is infected at any time. However, due to globalization, interaction and competition between lineages might increase, potentially leading to increased diversification and pathogenicity. Thus, endemic viruses appear to merit global attention with respect to the prevention of future pandemics.