admin In a study published Monday in Nature Microbiology, microbiologist Jan Carette of Stanford University and his colleagues report they have found a human gene that produces a protein essential to the function of numerous enteroviruses, a genus that includes rhinoviruses. Experiments in human cells and mice showed a range of enteroviruses cannot replicate without this host protein. The work could pave the way for antivirals effective against multiple illnesses—including most cases of the common cold—and sheds new light on how viruses exploit their host’s own cellular material. Carette and his colleagues have “done a tour de force here, to find this gene and characterize it,” says Ann Palmenberg, a virologist at the University of Wisconsin-Madison, who provided some advice and materials for the study but was not directly involved in it. “It’s a beautiful piece of work.”
Enteroviruses also include poliovirus, coxsackievirus (which causes myocarditis, or heart inflammation) and EV-D68, a virus that has been linked to acute flaccid myelitis. To search for commonalities between these viruses, the researchers used cutting-edge gene-editing technology to inactivate single genes from human cells grown in a lab dish. First they created a bank of cells that each lacked a different gene, spanning the whole human genome. Then they infected these cells with two enteroviruses: EV-D68 and a “type-C” rhinovirus called RV-C15. The latter is a fairly newly discovered rhinovirus type that can seriously exacerbate asthma symptoms and increase the risk of infected infants developing asthma and chronic obstructive pulmonary disease. Although they are both enteroviruses, EV-D68 and RV-C15 are relatively distant relations that mostly make use of different host-cell proteins. The team then looked at which genes were missing in cells that continued to flourish after infection, focusing on the few whose absence thwarted both viruses. In addition to two genes that produce proteins known to be needed by enteroviruses, one little known one stood out: SETD3, which makes a protein of the same name.
The researchers next tried to identify why the viruses need the SETD3 protein. They ruled out its normal function (the actin-modifying role), raising hopes that it could be targeted in ways that do not interfere with this function. Beyond that, they only narrowed it down to something to do with replication. Viruses use a combination of their own components and parts they pillage from the cell to build a “replication complex” that acts like a copy machine. “The virus gets in, but it can’t start making photocopies of itself,” Carette says. “It requires this SETD3 as an essential part of this photocopier.”
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