The human immune system's defense mechanism against HIV-1 and herpes simplex virus-1 has been further elucidated by researchers at the VIB-UGent Center for Medical Biotechnology. The study, led by Xavier Saelens and Sven Eyckerman, reveals how the MX protein, an interferon-stimulated gene (ISG) product, disrupts viral infections by assembling structures that mimic nuclear pore complexes, effectively trapping and disarming the viruses.
The innate immune system responds to viral infections by producing interferons, which activate antiviral defenses, including ISGs. The MX protein, discovered 60 years ago, is known to restrict a broad range of viruses, including HIV and herpes. However, the precise mechanism behind its antiviral properties has remained unclear until now.
MX Protein as a Viral Decoy
The research demonstrates that the MX protein drives the assembly of virus decoy structures that mimic nuclear pore complexes. These complexes are essential for viruses like herpes and HIV to deliver their genome into the host cell nucleus, hijack the cell's machinery, and propagate.
Sven Eyckerman explains, "We noticed that incoming viruses were being lured into structures that resembled nuclear pores. Through proteomics screens, we found that the MX protein interacts with proteins that are part of the nuclear pore complex... Viruses mistake these condensates for the actual cell door to the cell nucleus and get trapped or punctured."
Implications for Antiviral Therapies
Xavier Saelens notes, "By tricking viruses into prematurely releasing their genetic material, the MX protein ultimately prevents the spread of viral infections. This discovery not only clarifies how MX proteins combat viruses but also opens up potential new avenues for antiviral therapies."
The study, published in Cell Host & Microbe, highlights the potential for developing novel antiviral strategies that target viral entry and replication mechanisms. By understanding how the MX protein disrupts viral infections, researchers can explore new therapeutic interventions to combat these and other viral diseases.
