+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

The Infectious Bronchitis Coronavirus Envelope Protein Alters Golgi pH To Protect the Spike Protein and Promote the Release of Infectious Virus



The Infectious Bronchitis Coronavirus Envelope Protein Alters Golgi pH To Protect the Spike Protein and Promote the Release of Infectious Virus



Journal of Virology 93(11):



Coronaviruses (CoVs) assemble by budding into the lumen of the early Golgi complex prior to exocytosis. The small CoV envelope (E) protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi membranes, and has cation channel activity in vitro The E protein from avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system, which require residues in the HD. Mutation of the HD of IBV E in a recombinant virus background results in impaired growth kinetics, impaired release of infectious virions, accumulation of IBV spike (S) protein on the plasma membrane compared to wild-type (WT) IBV-infected cells, and aberrant cleavage of IBV S on virions. We previously reported the formation of two distinct oligomeric pools of IBV E in transfected and infected cells. Disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. Here, we present evidence suggesting that the monomeric form of IBV E correlates with an increased Golgi luminal pH. Infection with IBV or expression of IBV E induces neutralization of Golgi pH, promoting a model in which IBV E alters the secretory pathway through interaction with host cell factors, protecting IBV S from premature cleavage and leading to the efficient release of infectious virus from the cells. This is the first demonstration of a coronavirus-induced alteration in the microenvironment of the secretory pathway.IMPORTANCE Coronaviruses are important human pathogens with significant zoonotic potential. Progress has been made toward identifying potential vaccine candidates for highly pathogenic human CoVs, including the use of attenuated viruses that lack the CoV E protein or express E mutants. However, no approved vaccines or antiviral therapeutics exist. Understanding the role of the CoV E protein in virus assembly and release is thus an important prerequisite for potential vaccines as well as in identifying novel antiviral therapeutics.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 066586048

Download citation: RISBibTeXText

PMID: 30867314

DOI: 10.1128/jvi.00015-19


Related references

The missing link in coronavirus assembly. Retention of the avian coronavirus infectious bronchitis virus envelope protein in the pre-Golgi compartments and physical interaction between the envelope and membrane proteins. Journal of Biological Chemistry 276(20): 17515-17523, 2001

Coronavirus infectious bronchitis virus partial amino terminal sequencing of spike polypeptide s 2 identifies the sequence arginylarginylphenylalanylarginylarginine at the cleavage site of the spike precursor propolypeptide of infectious bronchitis virus strains beaudette and m 41. Virus Research 4(2): 133-144, 1986

The hydrophobic domain of infectious bronchitis virus E protein alters the host secretory pathway and is important for release of infectious virus. Journal of Virology 85(2): 675-685, 2011

Coronavirus avian infectious bronchitis virus structural characterization of the spike protein. Journal of General Virology 64(12): 2577-2584, 1983

Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins. Plos Pathogens 14(4): E1007009, 2018

Cloning and sequencing of the gene encoding the spike protein of the coronavirus infectious bronchitis virus. Journal of General Virology 66(4): 719-726, 1985

Mutations in the spike protein required for cross-species adaptation of the coronavirus, infectious bronchitis virus. Abstracts of the General Meeting of the American Society for Microbiology 101: 693, 2001

Oral immunization with a novel attenuated Salmonella Gallinarum encoding infectious bronchitis virus spike protein induces protective immune responses against fowl typhoid and infectious bronchitis in chickens. Veterinary Research 49: 91, 2018

Mapping of the receptor-binding domain and amino acids critical for attachment in the spike protein of avian coronavirus infectious bronchitis virus. Virology 448: 26-32, 2014

Identification of N-linked glycosylation sites in the spike protein and their functional impact on the replication and infectivity of coronavirus infectious bronchitis virus in cell culture. Virology 513: 65-74, 2018

A single amino acid mutation in the spike protein of coronavirus infectious bronchitis virus hampers its maturation and incorporation into virions at the nonpermissive temperature. Virology 326(2): 288-298, 2004

Infectious bronchitis virus E protein is targeted to the Golgi complex and directs release of virus-like particles. Journal of Virology 74(9): 4319-4326, 2000

Infectious Bronchitis Virus E Protein Is Targeted to the Golgi Complex and Directs Release of Virus-Like Particles. Journal of Virology 74(9): 4319-4326, 2000

Proteolytic activation of the spike protein at a novel RRRR/S motif is implicated in furin-dependent entry, syncytium formation, and infectivity of coronavirus infectious bronchitis virus in cultured cells. Journal of Virology 83(17): 8744-8758, 2009

Heat shock protein 70 in lung and kidney of specific-pathogen-free chickens is a receptor-associated protein that interacts with the binding domain of the spike protein of infectious bronchitis virus. Archives of Virology 162(6): 1625-1631, 2017