Primate hemorrhagic fever-causing arteriviruses are poised for spillover to humans

doi:10.1016/j.cell.2022.09.022

Cell

Volume 185, Issue 21, 13 October 2022, Pages 3980-3991.e18

https://doi.org/10.1016/j.cell.2022.09.022 Get rights and content

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Highlights

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SHFV uses an intracellular receptor, CD163, for cellular entry
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CD163 divergence in primates of some species poses a barrier to SHFV entry
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All cellular proteins required for SHFV replication are functional in human cells
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SHFV replication in human cells suggests potential for zoonotic transmission

Summary

Simian arteriviruses are endemic in some African primates and can cause fatal hemorrhagic fevers when they cross into primate hosts of new species. We find that CD163 acts as an intracellular receptor for simian hemorrhagic fever virus (SHFV; a simian arterivirus), a rare mode of virus entry that is shared with other hemorrhagic fever-causing viruses (e.g., Ebola and Lassa viruses). Further, SHFV enters and replicates in human monocytes, indicating full functionality of all of the human cellular proteins required for viral replication. Thus, simian arteriviruses in nature may not require major adaptations to the human host. Given that at least three distinct simian arteriviruses have caused fatal infections in captive macaques after host-switching, and that humans are immunologically naive to this family of viruses, development of serology tests for human surveillance should be a priority.

Graphical abstract

Keywords

hemorrhagic fever

arteriviruses

CD163 receptor

disease emergence

virus evolution

primates

virus entry

arms race

positive selection

zoonosis

Data and code availability

Primate CD163 sequences have been deposited at GenBank and are publicly available as of the date of publication. Co-localization analyses (Pearson's Correlation Coefficients [PCC]) were performed using a custom MatLab script. Accession numbers and code are listed in the key resources table. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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⁵: Present address: Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA

⁶: Present address: Inotiv, Boulder, CO 80301, USA

⁷: Present address: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA

⁸: Present address: Janssen Research & Development, Johnson & Johnson, Brisbane, CA 94005, USA

⁹: Present address: Department of Clinical Sciences, North Carolina State University, Raleigh, NC 27607, USA

¹⁰: Lead contact