Journal News

Scientists sweep cellular neighborhoods where Zika hides out

Laurel Oldach
Oct. 1, 2018

Most people infected with Zika never show symptoms. But the virus sometimes causes severe disability — from microcephaly in babies to weakness or partial paralysis in adults — and there is no treatment. In a paper in the journal Molecular & Cellular Proteomics, researchers report a comprehensive study of how the virus interacts with host cells. One of their findings gives insight into how Zika escapes immune signaling and proliferates inside the body.

This space-fill drawing shows the outside of one Zika virus particle (red and pink) and a cross-section through another as it interacts with a cell. Courtesy of David Goodsell/Wikimedia Commons

Like most viruses, Zika accomplishes a lot with a few tools. It has just one protein coding gene, which produces a single polypeptide that’s cleaved into 10 smaller proteins — a number dwarfed by the estimated 20,000 protein-coding genes in a human cell. Nevertheless, Zika can take over the vastly more complex human cell, repurposing it into a virus factory. Brian Raught, a researcher at the University of Toronto, said he found that process fascinating.

“With just these 10 proteins, this crazy virus turns your cells into zombies that do its bidding,” Raught said. “I always found that mind-blowing.”

Researchers in Raught’s lab, led by postdoctoral fellow Etienne Coyaud, wanted to find out how the handful of Zika proteins were able to hijack the host cell. They knew that the feat must depend on physical interactions between viral proteins and proteins native to the cell — but which ones?

Because of the increasing evidence linking Zika infections in expectant mothers to microcephaly in their children, Raught said, “We thought it better to leave the actual virus work to the experts.”

Instead of using infectious material, the team made 10 strains of human cells, each expressing one of Zika’s 10 proteins. By adding a small epitope tag to each viral protein, they were able to retrieve the viral proteins using an antibody that binds to this tag. The host proteins that stuck tightly to each viral protein came along for the ride; the researchers used mass spectrometry to identify those human proteins.

But there was a drawback to using this approach. What if proteins from the human cell were interacting with Zika proteins but separating from them before being extracted? To identify proteins that are close to but not inseparably intertwined with each viral protein, the team used a second technique called proximity labeling. In essence, they rigged each viral protein with an enzyme that would attach a sticky biotin tag onto anything that came close enough.

Proximity labeling is especially useful for detecting interactions with proteins embedded in cell membranes; those molecules are notoriously difficult to isolate.

“This is a really big asset of a proximity-labeling approach compared to traditional approaches,” Coyaud said.

Because Zika, like many viruses, enters the cell in a membrane-bound envelope and reorganizes many of its host’s membrane-bound organelles in the course of infection, its interactions with membrane proteins might be key to understanding the viral life cycle.

Enjoy reading ASBMB Today?

Become a member to receive the print edition monthly and the digital edition weekly.

Learn more
Laurel Oldach

Laurel Oldach is a former science writer for the ASBMB.

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Evolutionary constraints on disordered proteins
Feature

Evolutionary constraints on disordered proteins

Dec. 5, 2022

Best of BMB 2022: “There’s evidence that there must be conservation of function — so how does this happen, if the sequence changes so much?”

COVID-19, preprints and journalists
Science Communication

COVID-19, preprints and journalists

Dec. 3, 2022

Researchers find that news stories often fail to mention when studies haven’t been peer reviewed.

From the journals: MCP
Journal News

From the journals: MCP

Dec. 2, 2022

Muscling in on a signaling pathway. Probing weaknesses in the T cell surface. Improving single-cell proteomics two ways. Read about papers on these topics recently published in the journal Molecular & Cellular Proteomics.

Unconventional phosphoinositide synthesis
Lipid News

Unconventional phosphoinositide synthesis

Nov. 29, 2022

Researchers uncover a clue to how disease-causing bacteria synthesize the tiny lipids known as 3-phosphoinositides to hijack host cells.

From the journals: JLR
Journal News

From the journals: JLR

Nov. 25, 2022

A new way to measure lipoprotein(a). A new source of metabolized cholesterol. A new way to count ceramides. Read about articles on these topics recently published in the Journal of Lipid Research.

How proteolysis controls the Legionnaires’ pathogen
Journal News

How proteolysis controls the Legionnaires’ pathogen

Nov. 24, 2022

The bacterium that causes this severe pneumonia has a biphasic life cycle that depends on regulation of protein homeostasis.