Blocking of ebolavirus spread through intercellular connections by an MPER-specific antibody depends on BST2/tetherin
Rodrigo I. Santos,
Philipp A. Ilinykh,
Colette A. Pietzsch,
Adam J. Ronk,
Kai Huang,
Natalia A. Kuzmina,
Fuchun Zhou,
James E. Crowe,
Alexander Bukreyev
Affiliations
Rodrigo I. Santos
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Galveston National Laboratory, Galveston, TX, USA
Philipp A. Ilinykh
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Galveston National Laboratory, Galveston, TX, USA
Colette A. Pietzsch
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Galveston National Laboratory, Galveston, TX, USA
Adam J. Ronk
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Galveston National Laboratory, Galveston, TX, USA
Kai Huang
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Galveston National Laboratory, Galveston, TX, USA
Natalia A. Kuzmina
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Galveston National Laboratory, Galveston, TX, USA
Fuchun Zhou
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Galveston National Laboratory, Galveston, TX, USA
James E. Crowe
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA; Corresponding author
Alexander Bukreyev
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Galveston National Laboratory, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Corresponding author
Summary: Ebola virus (EBOV) and Bundibugyo virus (BDBV) belong to the family Filoviridae and cause a severe disease in humans. We previously isolated a large panel of monoclonal antibodies from B cells of human survivors from the 2007 Uganda BDBV outbreak, 16 survivors from the 2014 EBOV outbreak in the Democratic Republic of the Congo, and one survivor from the West African 2013–2016 EBOV epidemic. Here, we demonstrate that EBOV and BDBV are capable of spreading to neighboring cells through intercellular connections in a process that depends upon actin and T cell immunoglobulin and mucin 1 protein. We quantify spread through intercellular connections by immunofluorescence microscopy and flow cytometry. One of the antibodies, BDBV223, specific to the membrane-proximal external region, induces virus accumulation at the plasma membrane. The inhibiting activity of BDBV223 depends on BST2/tetherin.
