Genetic depletion studies inform receptor usage by virulent hantaviruses in human endothelial cells

نویسندگان

چکیده

Hantaviruses are RNA viruses with known epidemic threat and potential for emergence. Several rodent-borne hantaviruses cause zoonoses accompanied by severe illness death. However, assessments of zoonotic risk the development countermeasures challenged our limited knowledge molecular mechanisms hantavirus infection, including identities cell entry receptors their roles in influencing viral host range virulence. Despite long-standing presumption that β3/β1-containing integrins major receptors, rigorous genetic loss-of-function evidence supporting requirement, decay-accelerating factor (DAF), is lacking. Here, we used CRISPR/Cas9 engineering to knockout candidate singly combination, a human endothelial line recapitulates properties primary microvascular cells, targets infection humans. The loss β3 integrin, β1 and/or DAF had little or no effect on large panel hantaviruses. By contrast, protocadherin-1, recently identified receptor some hantaviruses, substantially reduced infection. We conclude molecules necessary PCDH1-independent remain be discovered.

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ژورنال

عنوان ژورنال: eLife

سال: 2021

ISSN: ['2050-084X']

DOI: https://doi.org/10.7554/elife.69708