Zika viruses encode 5′ upstream open reading frames affecting infection of human brain cells

Charlotte Lefèvre, Georgia M. Cook, Adam M. Dinan, Shiho Torii, Hazel Stewart, George Gibbons, Alex S. Nicholson, Liliana Echavarría-Consuegra, Luke W. Meredith, Valeria Lulla, Naomi McGovern, Julia C. Kenyon, Ian Goodfellow, Janet E. Deane, Stephen C. Graham, András Lakatos, Louis Lambrechts, Ian Brierley and Nerea Irigoyen ()
Additional contact information
Charlotte Lefèvre: University of Cambridge
Georgia M. Cook: University of Cambridge
Adam M. Dinan: University of Cambridge
Shiho Torii: Insect-Virus Interactions Unit
Hazel Stewart: University of Cambridge
George Gibbons: University of Cambridge
Alex S. Nicholson: University of Cambridge
Liliana Echavarría-Consuegra: University of Cambridge
Luke W. Meredith: University of Cambridge
Valeria Lulla: University of Cambridge
Naomi McGovern: University of Cambridge
Julia C. Kenyon: University of Cambridge
Ian Goodfellow: University of Cambridge
Janet E. Deane: University of Cambridge
Stephen C. Graham: University of Cambridge
András Lakatos: University of Cambridge
Louis Lambrechts: Insect-Virus Interactions Unit
Ian Brierley: University of Cambridge
Nerea Irigoyen: University of Cambridge

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Zika virus (ZIKV), an emerging mosquito-borne flavivirus, is associated with congenital neurological complications. Here, we investigate potential pathological correlates of virus gene expression in representative ZIKV strains through RNA sequencing and ribosome profiling. In addition to the single long polyprotein found in all flaviviruses, we identify the translation of unrecognised upstream open reading frames (uORFs) in the genomic 5′ region. In Asian/American strains, ribosomes translate uORF1 and uORF2, whereas in African strains, the two uORFs are fused into one (African uORF). We use reverse genetics to examine the impact on ZIKV fitness of different uORFs mutant viruses. We find that expression of the African uORF and the Asian/American uORF1 modulates virus growth and tropism in human cortical neurons and cerebral organoids, suggesting a potential role in neurotropism. Although the uORFs are expressed in mosquito cells, we do not see a measurable effect on transmission by the mosquito vector in vivo. The discovery of ZIKV uORFs sheds new light on the infection of the human brain cells by this virus and raises the question of their existence in other neurotropic flaviviruses.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53085-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53085-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53085-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().