The common cold is an infection of the upper respiratory tract that may be caused by many different viruses, but most frequently by rhinoviruses. A compound that inhibits a cell enzyme and blocks rhinovirus replication has the potential to be developed into an antiviral drug (link to paper).
Erin Garcia joins the TWiVirions to discuss a computer exploit encoded in DNA, creation of pigs free of endogenous retroviruses, and mutations in the gene encoding an innate sensor of RNA in children with severe viral respiratory disease.
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On episode #374 of the science show This Week in Virology,Â the TWiVniks consider the roleÂ of a cell enzyme that removesÂ a protein linked to the 5′-end of the picornavirus genome, and the connection between malaria, Epstein-Barr virus, and endemic Burkitt’s lymphoma.
You can find TWiV #374 at microbe.tv/twiv.
Rhinovirus is theÂ most frequent cause of the common cold, and the virus itself is quite common: there are over 160 types, classified into 3 species. The cell receptor has just been identified for the rhinovirus C species, which can cause more severe illness than members of the A or B species: it is cadherin-related family member 3.
Because viruses are obligate intracellular parasites, the genome must enter a cell before new particles can be made. The first step in this process is binding of the virus particle to a receptor on the plasma membrane. Two different membrane proteins serve as receptors for members of rhinovirus A and B species: intracellular adhesion molecule 1, and low-density lipoprotein receptor (illustrated).
It has not been possible to propagate species C rhinoviruses in conventional cell cultures, which has hampered research on how the virus replicates. The lack of a cell culture system required a different approach to identifying a cell receptor for this virus. It was known that the virus replicates in primary organ or cell cultures derived from sinus tissue, but not in a variety of epithelial and transformed cell lines (e.g. HeLa cells). In silico comparison of gene expression profiles revealed 400 genes that are preferentially expressed in virus-susceptible cells. This list was narrowed down to 12 genes that encode plasma membrane proteins. A subset of these genesÂ were introduced into cells and tested for the ability to serve as aÂ rhinovirus C receptor. Introduction of the gene encoding cadherin-related family member 3 (CDHR3) into HeLa cells allowed rhinovirus C binding and infection.
The cadherin family comprises cell surface proteins that are involved in cell-cell communication. The exact cell function of CDHR3 is not known, but the protein is found in human lung, bronchial epithelium, and cultured airway epithelial cells. A mutation in the gene encoding this protein is associated with wheezing illness and asthma in children. This mutation, which causes a change from cysteine to tyrosine at amino acid 529, was found to increase virus binding and virus replication inÂ HeLa cells that synthesize CDHR3. It will be important to determine if this amino acid change increases rhinovirus C replication in humans, thereby leading to more serious respiratory illness.
The CDHR3 gene was used to establishÂ a stable HeLa cell line that produces the receptor and which can be infected with species C rhinoviruses. This cell line will be useful for illuminating the details of viral replication in cells, which has so far been elusive due to lack of a susceptible and permissive cell line. It may also be possible to produce transgenic mice with the human CDHR3 gene, which could serve as a model for studying rhinovirus C pathogenesis. Transgenic mice that produce the receptor for the related polioviruses, CD155, are a model for poliomyelitis.
On episode #328 of the science show This Week in Virology, the TWiVocateurs discuss how the RNA polymerase of enteroviruses binds a component of the splicing machinery and inhibits mRNA processing.
You can find TWiV #328 at www.microbe.tv/twiv.
On episode #318 of the science show This Week in Virology, the TWiV gang reviews ten fascinating, compelling, and riveting virology stories from 2014.
You can find TWiV #318 at www.microbe.tv/twiv.