Structure-guided identification of a non-human morbillivirus with zoonotic potential
| Autor: | Vassiliy N. Bavro, Stephen C. Graham, Margaret J Hosie, Nicola S Logan, Daniel Gonçalves-Carneiro, Nurshariza Abdullah, Katrina A. Lythgoe, Jamie Birch, Dalan Bailey, Michael P. Heaton, Brian J. Willett, Robin N Thompson, James T. Kelly, Timothy J. Mitchell |
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| Přispěvatelé: | Bailey, Dalan [0000-0002-5640-2266], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Protein Conformation viruses Immunology Hemagglutinin (influenza) host range Sequence Homology Biology Antibodies Viral Virus Replication Microbiology Rinderpest virus Virus Peste-des-petits-ruminants virus Measles virus 03 medical and health sciences paramyxovirus Morbillivirus Signaling Lymphocytic Activation Molecule Family Member 1 Viral entry Virology Chlorocebus aethiops Peste-des-Petits-Ruminants measles Animals Humans Amino Acid Sequence Vero Cells Glycoproteins Sheep Models Theoretical biology.organism_classification 3. Good health Virus-Cell Interactions zoonoses morbillivirus 030104 developmental biology Viral replication Insect Science Mutation biology.protein Mutagenesis Site-Directed PPRV |
| Zdroj: | Journal of Virology |
| ISSN: | 0022-538X |
| DOI: | 10.1128/jvi.01248-18 |
| Popis: | A significant proportion of viral pandemics occur following zoonotic transmission events, where animal-associated viruses jump species into human populations. In order to provide forewarnings of the emergence of these viruses, it is necessary to develop a better understanding of what determines virus host range, often at the genetic and structural levels. In this study, we demonstrated that the small-ruminant morbillivirus, a close relative of measles, is unable to use human receptors to enter cells; however, a change of a single amino acid in the virus is sufficient to overcome this restriction. This information will be important for monitoring this virus’s evolution in the field. Of note, this study was undertaken in vitro, without generation of a fully infectious virus with this phenotype. Morbilliviruses infect a broad range of mammalian hosts, including ruminants, carnivores, and humans. The recent eradication of rinderpest virus (RPV) and the active campaigns for eradication of the human-specific measles virus (MeV) have raised significant concerns that the remaining morbilliviruses may emerge in so-called vacated ecological niches. Seeking to assess the zoonotic potential of nonhuman morbilliviruses within human populations, we found that peste des petits ruminants virus (PPRV)—the small-ruminant morbillivirus—is restricted at the point of entry into human cells due to deficient interactions with human SLAMF1—the immune cell receptor for morbilliviruses. Using a structure-guided approach, we characterized a single amino acid change, mapping to the receptor-binding domain in the PPRV hemagglutinin (H) protein, which overcomes this restriction. The same mutation allowed escape from some cross-protective, human patient, anti-MeV antibodies, raising concerns that PPRV is a pathogen with zoonotic potential. Analysis of natural variation within human and ovine SLAMF1 also identified polymorphisms that could correlate with disease resistance. Finally, the mechanistic nature of the PPRV restriction was also investigated, identifying charge incompatibility and steric hindrance between PPRV H and human SLAMF1 proteins. Importantly, this research was performed entirely using surrogate virus entry assays, negating the requirement for in situ derivation of a human-tropic PPRV and illustrating alternative strategies for identifying gain-of-function mutations in viral pathogens. IMPORTANCE A significant proportion of viral pandemics occur following zoonotic transmission events, where animal-associated viruses jump species into human populations. In order to provide forewarnings of the emergence of these viruses, it is necessary to develop a better understanding of what determines virus host range, often at the genetic and structural levels. In this study, we demonstrated that the small-ruminant morbillivirus, a close relative of measles, is unable to use human receptors to enter cells; however, a change of a single amino acid in the virus is sufficient to overcome this restriction. This information will be important for monitoring this virus’s evolution in the field. Of note, this study was undertaken in vitro, without generation of a fully infectious virus with this phenotype. |
| Databáze: | OpenAIRE |
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