Unmasking the Communicative Dance of Viruses and Cells

Influenza viruses are prime candidates for triggering future pandemics, and groundbreaking research from the Helmholtz Center for Infection Research (HZI) and the Medical Center—University of Freiburg has opened a window into how these viruses interact with host cells in incredible detail.

A Novel Approach to Seek and Seize

Using an innovative method, the team has unraveled how new strains of influenza exploit alternative receptors to infiltrate target cells. Their remarkable findings were recently published in the prestigious journal Nature Communications.

The Virus-Cell Connection: A Critical First Step

Viruses lack their own metabolism and rely entirely on infecting host cells to reproduce. The initial contact between the virus and a host cell's surface is crucial; blocking this interaction could prevent infections altogether. "The process is dynamic and fleeting for influenza viruses, requiring super-resolution microscopes to investigate accurately," explains Prof. Christian Sieben, who leads the junior research group "Nano Infection Biology" at HZI.

Innovative Experimental Techniques Challenge Traditional Methods

Collaborating with Prof. Mark Brönstrup's team, Sieben's group has created a universal protocol for studying virus-host communication. They immobilized viruses individually on glass slides, then placed cells on top, a method that stabilizes the critical moment of initial contact.

"Our upside-down approach allows us to observe how viruses interact with cells without entering them—providing a unique viewpoint on this crucial interaction," says Sieben.

Decoding the Viral Invasion: A Cascade of Cellular Reactions

Through high-resolution microscopy, the scientists discovered that when an influenza A virus contacts a cell, it triggers a cascade of cellular responses. Receptors locally gather at the viral binding site, followed by a recruitment of specific proteins and a dynamic reorganization of the actin cytoskeleton. This sequence is pivotal for the virus’s entry.

Exploring Novel Strains: The H18N11 Virus

The researchers didn’t stop at conventional strains—they also examined the H18N11 virus, a novel influenza type found in bats. Uniquely, this virus binds to MHC class II complexes, typically associated with immune cells.

Dr. Peter Reuther, who leads research on bat-derived influenza at the University of Freiburg, reveals, "Upon contact, MHCII molecules cluster on the cell surface, a vital step for the virus’s invasion. This finding is groundbreaking in understanding alternative receptors for influenza viruses."

Opening New Avenues for Research

This dual discovery reshapes our understanding of influenza infections, suggesting that these viruses do not exclusively bind to cellular glycans as previously thought. Such insights are vital, especially given the zoonotic potential of these pathogens.

The Future of Antiviral Research

The focus on virus-cell binding is also central to the upcoming EU project COMBINE, set to launch in early 2025, where scientists from five countries will explore the entry processes of emerging viruses with pandemic potentials.

"Understanding how viruses enter cells presents exciting avenues for antiviral therapies. Our methodology could be applied beyond influenza, paving the way for new therapeutic targets," concludes Sieben.

A Promising Leap Forward