✍🏼 Megan M. Slough, Rong Li, Andrew S. Herbert, Gorka Lasso, Ana I. Kuehne, Stephanie R. Monticelli, Russell R. Bakken, Yanan Liu, Agnidipta Ghosh, Alicia M. Moreau, Xiankun Zeng, Félix A. Rey, Pablo Guardado-Calvo, Steven C. Almo, John M. Dye, Rohit K. Jangra, Zhongde Wang & Kartik Chandran
🏠 Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
📑 Nature Communications (2023)
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Abstract
Andes virus (ANDV) and Sin Nombre virus (SNV) are the etiologic agents of severe hantavirus cardiopulmonary syndrome (HCPS) in the Americas for which no FDA-approved countermeasures are available. Protocadherin-1 (PCDH1), a cadherin-superfamily protein recently identified as a critical host factor for ANDV and SNV, represents a new antiviral target; however, its precise role remains to be elucidated. Here, we use computational and experimental approaches to delineate the binding surface of the hantavirus glycoprotein complex on PCDH1’s first extracellular cadherin repeat domain. Strikingly, a single amino acid residue in this PCDH1 surface influences the host species-specificity of SNV glycoprotein-PCDH1 interaction and cell entry. Mutation of this and a neighboring residue substantially protects Syrian hamsters from pulmonary disease and death caused by ANDV. We conclude that PCDH1 is a bona fide entry receptor for ANDV and SNV whose direct interaction with hantavirus glycoproteins could be targeted to develop new interventions against HCPS.
How the WOLF was used in this study
The WOLF Cell Sorter was used to enrich specific cell populations for downstream experimental analyses. After genetic manipulation and expression of wild-type or mutant Protocadherin-1 (PCDH1) in engineered cell lines, researchers typically sort cells based on fluorescent markers or surface expression to obtain homogeneous populations of cells expressing the targeted PCDH1 variants. The WOLF sorter’s gentle, low-pressure microfluidic sorting preserves cell viability and functional integrity, enabling accurate downstream assays
