Crimean–Congo haemorrhagic fever virus S-segment mRNA 5′ UTR functions as an internal ribosome entry site-like element in an N protein-dependent manner
- 1College of Veterinary Medicine, Western University of Health Sciences, Pomona, California, USA
- 2Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California, USA
Abstract
The Crimean–Congo haemorrhagic fever virus nucleocapsid (N) protein contains structurally distinct stalk and head domains. The mRNA encoding N protein (NP) possesses a 55-nt 5′ UTR that folds into a stable hairpin structure. We previously demonstrated that the NP preferentially promotes translation of its own mRNA by simultaneously binding the 5′ UTR hairpin via its stalk domain and the translation initiation factor eIF4A via its head domain. This coordinated interaction facilitates selective ribosome recruitment to the 5′ UTR and enhances translation of the downstream ORF. In this study, we further show that the S-segment 5′ UTR functions as an internal ribosome entry site (IRES)-like element when inserted between two ORFs, promoting downstream translation in an NP-dependent manner. Expression of a dual-reporter transcript containing the S-segment 5′ UTR in Hazara virus-infected cells inhibited viral replication by competing for NP binding. In contrast, randomization of the 5′ UTR abolished NP binding, IRES-like activity and antiviral effects. Unlike the S segment, the L- and M-segment 5′ UTRs do not form the requisite hairpin structure, fail to bind NP and cannot support NP-mediated translation. These findings suggest that structurally similar elements within host mRNAs may also be selectively translated during infection.
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BibTeX
@article{ren2026crimeancongo,
title = {{Crimean–Congo haemorrhagic fever virus S-segment mRNA 5′ UTR functions as an internal ribosome entry site-like element in an N protein-dependent manner}},
author = {Songyang Ren and Ethan Mir and Hoangvi Le and Saima Ali and Sheema Mir and Mohammad Mir},
journal = {The Journal of General Virology},
year = {2026},
month = oct,
doi = {10.1099/jgv.0.002359},
url = {https://doi.org/10.1099/jgv.0.002359},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Crimean–Congo haemorrhagic fever virus S-segment mRNA 5′ UTR functions as an internal ribosome entry site-like element in an N protein-dependent manner
AU - Songyang Ren
AU - Ethan Mir
AU - Hoangvi Le
AU - Saima Ali
AU - Sheema Mir
AU - Mohammad Mir
PY - 2026
DA - 2026/10/27
JO - The Journal of General Virology
DO - 10.1099/jgv.0.002359
UR - https://doi.org/10.1099/jgv.0.002359
AB - The Crimean–Congo haemorrhagic fever virus nucleocapsid (N) protein contains structurally distinct stalk and head domains. The mRNA encoding N protein (NP) possesses a 55-nt 5′ UTR that folds into a stable hairpin structure. We previously demonstrated that the NP preferentially promotes translation of its own mRNA by simultaneously binding the 5′ UTR hairpin via its stalk domain and the translation initiation factor eIF4A via its head domain. This coordinated interaction facilitates selective ribosome recruitment to the 5′ UTR and enhances translation of the downstream ORF. In this study, we further show that the S-segment 5′ UTR functions as an internal ribosome entry site (IRES)-like element when inserted between two ORFs, promoting downstream translation in an NP-dependent manner. Expression of a dual-reporter transcript containing the S-segment 5′ UTR in Hazara virus-infected cells inhibited viral replication by competing for NP binding. In contrast, randomization of the 5′ UTR abolished NP binding, IRES-like activity and antiviral effects. Unlike the S segment, the L- and M-segment 5′ UTRs do not form the requisite hairpin structure, fail to bind NP and cannot support NP-mediated translation. These findings suggest that structurally similar elements within host mRNAs may also be selectively translated during infection.
SN - 0022-1317
SN - 1465-2099
ER -