The long-lasting enigma of polycytidine (polyC) tract
Open accessAbstract
Long polycytidine (polyC) tracts varying in length from 50 to 400 nucleotides were first described in the 5′-noncoding region (NCR) of genomes of picornaviruses belonging to the Cardio- and Aphthovirus genera over 50 years ago, but the molecular basis of their function is still unknown. Truncation or complete deletion of the polyC tracts in picornaviruses compromises virulence and pathogenicity but do not affect replicative fitness in vitro, suggesting a role as “viral security” RNA element. The evidence available suggests that the presence of a long polyC tract is required for replication in immune cells, which impacts viral distribution and targeting, and, consequently, pathogenic progression. Viral attenuation achieved by reduction of the polyC tract length has been successfully used for vaccine strategies. Further elucidation of the role of the polyC tract in viral replication cycle and its connection with replication in immune cells has the potential to expand the arsenal of tools in the fight against cancer in oncolytic virotherapy (OV). Here, we review the published data on the biological significance and mechanisms of action of the polyC tract in viral pathogenesis in Cardio- and Aphthoviruses.
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There is the potential for the length of the polyC tract to be artificially altered by cell culture passaging.
“However, as there is the potential for the length of the polyC tract to be artificially altered by cell culture passaging [37,40], future attempts at direct RNA sequencing should be made using fresh tissue when available.”
From Zoological transmission of encephalomyocarditis virus in the United States: Virus evolution, host ecology, and capsid antigenicity derived from an outbreak (2026) · cites this paper as [37]
The initial lengths of the polyC tracts in the 5' UTR, which ranged from 14-25 nt, are inaccurate due to the inability of polymerases used in RNA-Seq to sequence long homopolymer stretches.
“As we performed cDNA synthesis for genome sequencing, the initial lengths of the polyC tracts in the 5’ UTR, which ranged from 14–25 nt, are inaccurate due to the inability of polymerases used in RNA-Seq to sequence long homopolymer stretches [37].”
From Zoological transmission of encephalomyocarditis virus in the United States: Virus evolution, host ecology, and capsid antigenicity derived from an outbreak (2026) · cites this paper as [37]
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Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
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Cited by
Sorted by citations
Adhikari, A., Feng, K. H., Shrestha, A., Rodriguez, C. E., Nolan, E. C., Pye, G. W., Gauger, P. C., Denagamage, T., Holmes, E. C., & Allison, A. B. (2026) · PLOS Pathogens · doi:10.1371/journal.ppat.1013861 · Cited by 1 · see citing works
“However, as there is the potential for the length of the polyC tract to be artificially altered by cell culture passaging [37,40], future attempts at direct RNA sequencing should be made using fresh tissue when available.”
- Authors
- Penza, V., Russell, S. J., & Schulze, A. J.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Schulze, Autumn J.
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2021-08-04
- Volume
- 17
- Issue
- 8
- Pages
- e1009739
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC8336851
- OpenAlex
- W3190179284
- Cited by
- 12
- References
- 120
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 1
- FWCI
- 0.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Mayo Clinic
- National Institutes of Health (CA207386)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- picornavirus, 5' untranslated region, viral attenuation, vaccine development, oncolytic virotherapy, viral pathogenesis, RNA secondary structure
- MeSH terms
- Animals, Aphthovirus, Humans, Poly C, Virus Replication, Cardiovirus, Oncolytic Virotherapy
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