The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
The Evolutionary Pathway to Virulence of an RNA Virus
Open accessAbstract
Paralytic polio once afflicted almost half a million children each year. The attenuated oral polio vaccine (OPV) has enabled world-wide vaccination efforts, which resulted in nearly complete control of the disease. However, poliovirus eradication is hampered globally by epidemics of vaccine-derived polio. Here, we describe a combined theoretical and experimental strategy that describes the molecular events leading from OPV to virulent strains. We discover that similar evolutionary events occur in most epidemics. The mutations and the evolutionary trajectories driving these epidemics are replicated using a simple cell-based experimental setup where the rate of evolution is intentionally accelerated. Furthermore, mutations accumulating during epidemics increase the replication fitness of the virus in cell culture and increase virulence in an animal model. Our study uncovers the evolutionary strategies by which vaccine strains become pathogenic and provides a powerful framework for rational design of safer vaccine strains and for forecasting virulence of viruses. VIDEO ABSTRACT.
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“This event is often observed in vivo in vaccinees that receive trivalent OPV (tOPV) (Korotkova et al., 2017, Stern et al., 2017).”
From Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence (2020) · cites this paper as Stern et al., 2017
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Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Soon after vaccination, the majority of vaccinees shed polioviruses with a high frequency of such mutations (Evans et al., 1985, Stern et al., 2017), indicating that the structural stability of domV is under strong positive selection in the human gut.”
From Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence (2020) · cites this paper as Stern et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recombination of an OPV strain with co-circulating enterovirus C species allowed the Sabin2 domV to be replaced by that of a WT co-circulating enterovirus to provide a thermostable structure, thereby restoring viral fitness (Burns et al., 2013, Stern et al., 2017).”
From Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence (2020) · cites this paper as Stern et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In all type 2 lineages in current outbreaks, the 481 A-to-G mutation preceded all other events leading to cVDPVs virulence (Stern et al., 2017), suggesting its role as a “gate-keeper” in the reversion process, similar to driver mutations in cancer evolution (Curigliano, 2018, Reddy et al., 2017, Temko et al., 2017).”
From Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence (2020) · cites this paper as Stern et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These thermoresistant variants also display a significant increase in virulence (Macadam et al., 2006, Stern et al., 2017).”
From Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence (2020) · cites this paper as Stern et al., 2017
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In the citing paper
“Strikingly, in the mouse neurovirulence test, the redesigned nOPV2 recovered from vaccinees maintained its attenuation phenotype (Van Damme et al., 2019), in contrast to the current vaccine containing Sabin2 (Stern et al., 2017).”
From Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence (2020) · cites this paper as Stern et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Mutation U459C (nucleotide 398 in Sabin2) was identified as a secondary adaptive mutation in cVDPV2 isolates and vaccinee isolates (Stern et al., 2017).”
From Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence (2020) · cites this paper as Stern et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Indeed, by 14 days post-vaccination, most Sabin2 vaccinees excrete virus mutants that lost the attenuation allele entirely in domV (Figures 7A and 7B) (Stern et al., 2017).”
From Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence (2020) · cites this paper as Stern et al., 2017
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In the citing paper
“A number of studies have identified three specific codon positions that are involved in this reversion, two in the 5′ UTR region and one in the VP1 region [82,83].”
From The Fight against Poliovirus Is Not Over (2023) · cites this paper as [82]
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In the citing paper
“A single A-to-G mutation at this position results in increased tolerance to temperature and makes the virus more neurovirulent (Macadam et al., 1992, Macadam et al., 1994, Stern et al., 2017).”
From Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence (2020) · cites this paper as Stern et al., 2017
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Citations
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Metadata
- Authors
- Stern, A., Yeh, M. T., Zinger, T., Smith, M., Wright, C., Ling, G., Nielsen, R., Macadam, A., & Andino, R.
- Affiliations
- Tel Aviv University (IL)
- University of California, San Francisco (US)
- National Institute for Biological Standards and Control (GB)
- University of California, Berkeley (US)
- Corresponding author
- Stern, Adi
- Andino, Raul
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 169
- Issue
- 1
- Pages
- 35-46.e19
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5787669
- OpenAlex
- W2598379945
- Cited by
- 127
- References
- 72
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 10 · 2023: 15 · 2022: 13 · 2021: 20 · 2020: 20 · 2019: 12 · 2018: 17 · 2017: 6
- FWCI
- 9.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 388 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- WIS post-doctoral award
- Rothschild post-doctoral award
- Edmond J. Safra Center for Bioinformatics at Tel-Aviv University
- NSF (CMMI-0941355)
- NIH (R01 GM097115, AI36178, AI40085, P01 AI091575)
- University of California (CCADD
- DARPA Prophecy
- Bill and Melinda Gates Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Immunology Research
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- poliovirus, vaccine-derived poliovirus, oral polio vaccine, RNA virus evolution, polio epidemic
- MeSH terms
- Animals, Biological Evolution, Phylogeny, Poliomyelitis, Poliovirus Vaccine, Oral, Poliovirus, Mice
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