Next Article in Journal
Expression of Two Foreign Genes from the Optimal Insertion Sites of Newcastle Disease Virus Vector for Use as a Multivalent Vaccine and Gene Therapy Vector
Previous Article in Journal
FDA Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses In Vitro
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Abstract

Mapping the Interface between New World Hantaviruses and Their Receptor, PCDH1 †

1
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA
*
Authors to whom correspondence should be addressed.
Presented at Viruses 2020—Novel Concepts in Virology, Barcelona, Spain, 5–7 February 2020.
Proceedings 2020, 50(1), 8; https://doi.org/10.3390/proceedings2020050008
Published: 3 June 2020
(This article belongs to the Proceedings of Viruses 2020—Novel Concepts in Virology)

Abstract

:
Hantaviruses are found throughout the world and can cause deadly diseases in humans, specifically, hantavirus cardiopulmonary syndrome (HCPS) in the New World and hemorrhagic fever with renal syndrome (HFRS) in the Old World. Currently, no FDA-approved, specific antiviral drugs or vaccines are available. Recently, we showed that New World hantaviruses utilize protocadherin-1 (PCDH1) for endothelial cell entry and infection by directly engaging its first extracellular cadherin repeat (EC1) domain. The knockout of PCDH1 also greatly reduced pulmonary infection and was highly protective in a Syrian hamster model of lethal challenge with Andes virus (ANDV). To further understand PCDH1’s role in hantavirus entry, we sought to map the binding interface between hantavirus Gn/Gc and PCDH1-EC1. Accordingly, we screened a panel of EC1 proteins, bearing point mutations in solvent-exposed residues, for their capacity to recognize Gn/Gc and block viral entry. EC1 mutations defective in Gn/Gc binding were engineered individually and in combinations into full-length PCDH1, expressed in PCDH1-knockout cells, and evaluated for their capacity to complement viral infection. We identified a surface in the PCDH1-EC1 domain, comprising contiguous residues, which was required for virus PCDH1 recognition and PCDH1-dependent viral entry. However, this region does not overlap with the EC1–EC4 heterodimer interface recently described by Modak and Sotomayor. In addition, through the use of recombinant vesicular stomatitis viruses bearing chimeric hantavirus Gn/Gc glycoproteins, we were able to pinpoint the importance of the N-terminal domain of the Gn subunit for PCDH1-mediated entry. With these taken together, identifying the location of the interface could provide a direction for the development of host-directed antiviral drugs that do not interfere with PCDH1’s endogenous function, as well as help to map an antigen target on Gn/Gc for antiviral antibodies.

Share and Cite

MDPI and ACS Style

Slough, M.M.; Herbert, A.S.; Kuehne, A.I.; Dye, J.M.; Chandran, K.; Jangra, R.K. Mapping the Interface between New World Hantaviruses and Their Receptor, PCDH1. Proceedings 2020, 50, 8. https://doi.org/10.3390/proceedings2020050008

AMA Style

Slough MM, Herbert AS, Kuehne AI, Dye JM, Chandran K, Jangra RK. Mapping the Interface between New World Hantaviruses and Their Receptor, PCDH1. Proceedings. 2020; 50(1):8. https://doi.org/10.3390/proceedings2020050008

Chicago/Turabian Style

Slough, Megan M., Andrew S. Herbert, Ana I. Kuehne, John M. Dye, Kartik Chandran, and Rohit K. Jangra. 2020. "Mapping the Interface between New World Hantaviruses and Their Receptor, PCDH1" Proceedings 50, no. 1: 8. https://doi.org/10.3390/proceedings2020050008

APA Style

Slough, M. M., Herbert, A. S., Kuehne, A. I., Dye, J. M., Chandran, K., & Jangra, R. K. (2020). Mapping the Interface between New World Hantaviruses and Their Receptor, PCDH1. Proceedings, 50(1), 8. https://doi.org/10.3390/proceedings2020050008

Article Metrics

Back to TopTop