TitleCX3CR1 Is a Receptor for Human Respiratory Syncytial Virus in Cotton Rats.
Publication TypeJournal Article
Year of Publication2021
AuthorsGreen, G, Johnson, SM, Costello, H, Brakel, K, Harder, O, Oomens, AG, Peeples, ME, Moulton, HM, Niewiesk, S
JournalJ Virol
Date Published2021 07 26
KeywordsAnimals, Antibodies, Viral, Binding Sites, Cell Line, CX3C Chemokine Receptor 1, Disease Models, Animal, Epithelial Cells, Heparitin Sulfate, Humans, Mutation, Receptors, Virus, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus, Human, Respiratory System, Sigmodontinae, Viral Envelope Proteins, Virus Replication

Respiratory syncytial virus (RSV) has been reported to use CX3CR1 as a receptor on cultured primary human airway epithelial cultures. To evaluate CX3CR1 as the receptor for RSV , we used the cotton rat animal model because of its high permissiveness for RSV infection. Sequencing the cotton rat CX3CR1 gene revealed 91% amino acid similarity to human CX3CR1. Previous work found that RSV binds to CX3CR1 via its attachment glycoprotein (G protein) to infect primary human airway cultures. To determine whether CX3CR1-G protein interaction is necessary for RSV infection, recombinant RSVs containing mutations in the CX3CR1 binding site of the G protein were tested in cotton rats. In contrast to wild-type virus, viral mutants did not grow in the lungs of cotton rats. When RSV was incubated with an antibody blocking the CX3CR1 binding site of G protein and subsequently inoculated intranasally into cotton rats, no virus was found in the lungs 4 days postinfection. In contrast, growth of RSV was not affected after preincubation with heparan sulfate (the receptor for RSV on immortalized cell lines). A reduction in CX3CR1 expression in the cotton rat lung through the use of peptide-conjugated morpholino oligomers led to a 10-fold reduction in RSV titers at day 4 postinfection. In summary, these results indicate that CX3CR1 functions as a receptor for RSV in cotton rats and, in combination with data from human airway epithelial cell cultures, strongly suggest that CX3CR1 is a primary receptor for naturally acquired RSV infection. The knowledge about a virus receptor is useful to better understand the uptake of a virus into a cell and potentially develop antivirals directed against either the receptor molecule on the cell or the receptor-binding protein of the virus. Among a number of potential receptor proteins, human CX3CR1 has been demonstrated to act as a receptor for respiratory syncytial virus (RSV) on human epithelial cells in tissue culture. Here, we report that the cotton rat CX3CR1, which is similar to the human molecule, acts as a receptor . This study strengthens the argument that CX3CR1 is a receptor molecule for RSV.

Alternate JournalJ Virol
PubMed ID34037420
PubMed Central IDPMC8312862
Grant ListP01 AI112524 / AI / NIAID NIH HHS / United States
R01 AI093848 / AI / NIAID NIH HHS / United States