'Spiderman' Cells Trap Viral Genomes With Sticky Protein Webs

Scientists have identified a cell defense mechanism that mimics Spiderman shooting his web to capture enemies.

Image credit: Vink FanShutterstock.com

In the earliest stages of viral infection, cells deploy a defence mechanism that resembles a sticky “web,” capable of trapping viral genomes and limiting their activity. This work, led by researchers from two Medical Research Council (MRC) units: the MRC-University of Glasgow Centre for Virus Research (CVR) and the University of Dundee’s MRC Protein Phosphorylation and Ubiquitylation Unit (PPU), reveals this response is activated within minutes of a virus entering a cell. 

By ensnaring viral genetic material, this mechanism helps disrupt the processes required for the virus to establish itself and begin replicating, representing a rapid and previously unrecognised strategy by which cells interfere with the initial steps of infection.

Superpower Protein

At the centre of this defence mechanism is a protein known as ZNFX1, which enables cells to regulate the earliest phases of viral infection and limit the potential for replication and spread. Researchers found that ZNFX1 is produced when a cell senses a virus in a neighbouring cell, priming it to respond rapidly to infection. 

In Hiding

Once inside the body, viruses attempt to establish a foothold by concealing their genetic material from detection while simultaneously hijacking essential cellular machinery to replicate, produce viral proteins, and assemble new viral particles. These newly formed particles are then released, allowing the infection to spread to additional cells or hosts. 

‘Passport Control’

To counter this, human cells rely on specialised “sensor” proteins that monitor incoming molecular material, functioning like passport control by screening what enters the cellular environment. ZNFX1 acts as one such sensor, scanning nucleic acids, DNA, and RNA, which form the genetic material of all living organisms, including viruses, and distinguishing between host and viral molecules. 

Ubiquitin

Beyond its role in detection, the researchers identified a second, unexpected function of ZNFX1: its ability to generate a Spiderman-like sticky “web” using chains of the molecule ubiquitin. These ubiquitin chains form a mesh that entraps viral genomes, disrupting their normal function and slowing viral replication. 

Mutation Risks

The importance of this mechanism is highlighted by the effects of mutations in the gene encoding ZNFX1, which are associated with severe autoimmune and neurological disorders and high mortality in affected children. The study found that some of these mutations impair the formation of the ubiquitin web, suggesting that this spider-like antiviral response plays a critical role in normal immune defence. 

ZNFX1

Ongoing research is now focused on understanding how ZNFX1 links viral genome detection to the formation of these antiviral webs. Current findings indicate that the webs are transient, persisting for only a few hours before disassembling, after which viral replication can resume.

Determining why this occurs may open new avenues for therapeutic intervention, potentially enabling the extension of web formation to further suppress, or even halt, viral replication. 

Virus ‘Speed Bump’

This is yet another elaborate way that the cell defends itself from viruses. By temporarily entrapping viral genomes, ZNFX1 seems to act like a ‘speed bump’ for the virus. Understanding how these antiviral webs form and why they dissolve would help us figure out whether they can be harnessed as antiviral medicines in the future.

Dr Adam Fletcher, Study Co-Lead and Future Leadership Senior Fellow, UK Research and Innovation (UKRI)

Therapeutic Medicines

Our cells are surprisingly adept at countering viral infections using highly sophisticated mechanisms, yet the battle is often lost. Understanding how these ‘built-in’ defences operate at the molecular level is crucial, as it can inform how they might be therapeutically modulated to treat infectious disease.

Satpal Virdee, Study Co-Lead and Professor, Chemical Biology, MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee