Differential PCDH1 usage by Laguna Negra and Black Creek Canal hantaviruses

Authors

Guerra-Pilaquinga, N., Word, C., Lambe, U. P., Khera, L., Arinola, R., Kaur, R., Dieterle, M. E., Jangra, R. K.

Abstract

Laguna Negra virus and Black Creek Canal virus are hantaviruses associated with hantavirus cardiopulmonary syndrome (HCPS), but their cellular entry receptors have not been defined. We used replication-competent recombinant vesicular stomatitis viruses (rVSVs) bearing hantavirus Gn/Gc glycoprotein complexes to compare entry by these viruses, the Old World rodent-borne Dabieshan virus and Tigray virus, and the shrew-borne Cao Bang virus and Amga virus. All six Gn/Gc complexes supported infection of primary human pulmonary microvascular endothelial cells, with virus-specific efficiencies and kinetics. Genetic ablation of protocadherin-1 (PCDH1) reduced infection mediated by Laguna Negra virus and Black Creek Canal virus Gn/Gc in human osteosarcoma and endothelial cells, whereas PCDH1 re-expression restored susceptibility. Both viruses were captured by a soluble PCDH1 protein comprising the first two extracellular cadherin domains. Infection was also inhibited by a soluble decoy containing the first cadherin domain, and by an antibody specific to that domain, indicating that the first PCDH1 cadherin domain mediates viral engagement. Black Creek Canal Gn/Gc-bearing rVSVs incorporated less Gn/Gc and showed lower apparent capture by PCDH1 than Laguna Negra virus and Andes virus Gn/Gc-bearing particles, even after normalization for glycoprotein abundance. In contrast, PCDH1 depletion did not detectably alter infection mediated by the other four hantavirus Gn/Gc complexes. Thus, Laguna Negra virus and Black Creek Canal virus use PCDH1 for efficient entry but differ in apparent receptor engagement and responses to PCDH1-directed inhibitors, whereas all six viruses are potently neutralized by the broadly reactive Gn/Gc-directed antibody ADI-42898.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 06 Oct 2026.

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