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A new study published in PLOS Pathogens reveals how monkeypox virus (MPXV) and its relatives outsmart the body’s early immune defenses. Infectious disease researchers from Wuhan University and the Wuhan Institute of Virology have discovered that a viral protein called OPG147 plays a key role in helping the virus hide from immune detection during the critical first hours of infection.

OPG147 is part of the machinery that allows poxviruses to enter cells, but this study shows it has a second job: disarming the host’s immune alarm system. The research sheds new light on how MPXV and related poxviruses—including vaccinia virus (VACV), used in smallpox vaccines—avoid triggering a strong antiviral response. These findings could help scientists develop better treatments and safer, more effective vaccines.

The disease caused by monkeypox virus is now officially called mpox, following a 2022 renaming by the World Health Organization to reduce stigma and improve public communication. While mpox refers to the illness, monkeypox virus (MPXV) remains the accepted scientific name for the virus itself.

What Is the MITA/STING Pathway—and Why Does It Matter?

Our bodies rely on innate immunity to recognize infections before symptoms even begin. One of the key systems in this early defense is the MITA/STING pathway. When a virus infects a cell and releases its DNA, a sensor called cGAS detects the foreign material and produces a molecule that activates MITA (also called STING, for STimulator of INterferon Genes). This sets off a chain reaction that results in the production of interferons and other antiviral proteins that help control the infection.

In short: MITA/STING is the body’s built-in alarm system for DNA viruses. Without it, the immune system may not respond quickly enough to stop the virus from spreading.

How the Virus Silences the Alarm

The study shows that OPG147 from monkeypox virus—and similar proteins in other poxviruses—can directly interfere with MITA/STING. OPG147 doesn’t block the initial detection of the virus. Instead, it quietly sabotages the steps needed for MITA/STING to activate a full immune response:

• OPG147 blocks a chemical process called ISGylation that helps MITA become fully active.
• It prevents MITA from forming the structures it needs to send out immune signals.
• It traps MITA inside the cell’s endoplasmic reticulum, stopping it from moving to the places where it would normally raise the alarm.

By interfering with these processes, OPG147 allows the virus to establish infection without alerting the immune system right away.

A Weak Spot in the Virus’s Armor

To test how important OPG147 is for the virus, researchers created a mutated version of vaccinia virus where OPG147 could no longer interact with MITA. They found that this altered virus:

• Triggered stronger immune responses in human cells and in mice.
• Produced lower levels of virus in the body.
• Caused milder disease and less tissue damage.
• Did not lose its ability to replicate, meaning the mutation specifically weakens the virus’s ability to evade immunity—not its basic life cycle.

These results show that OPG147 is a key virulence factor—critical for helping the virus cause disease.

Why This Matters for Public Health and National Security

Although mpox is no longer a rare disease, it continues to pose a public health and global security challenge, especially for immunocompromised individuals and in regions with limited access to vaccines and treatments. In addition, orthopoxviruses remain a concern for potential biosecurity threats.

This research identifies OPG147 as a potential weak point that could be targeted by new antiviral drugs or used to develop safer, more effective vaccines. For public health agencies and global health security planners, this study provides valuable insights into how poxviruses evade immune detection—a crucial piece of knowledge for surveillance, outbreak response, and vaccine development.

A New Direction for Vaccine and Antiviral Strategies

What makes OPG147 especially interesting is that it works differently from other known poxvirus immune blockers. While some viral proteins destroy the molecules that signal an immune response, OPG147 directly jams the signaling machinery, making it harder for the immune system to detect the infection in time.

This strategy shows just how sophisticated viruses can be in evading immune defenses—and it suggests that combining treatments that target multiple viral evasion proteins may offer stronger protection.

Zhou X, Liu Z, Shi W, et al. The conserved poxvirus membrane entry-fusion apparatus component OPG147 targets MITA/STING for immune evasion. PLOS Pathogens. June 11, 2025.

In a recent analysis led by Ryan Hankins, MD, urologist at MedStar Georgetown University Hospital in Washington, DC, researchers explored a compelling new angle on the use of rectal spacers during prostate cancer radiotherapy. While rectal spacers have long been used to reduce rectal toxicity from radiation therapy, emerging evidence suggests their benefits may extend further, including a potential impact on erectile dysfunction (ED) outcomes.

“We use rectal spacers to help prevent [adverse events] from radiation therapy for prostate cancer. The spacers [were] developed to help with rectal toxicity, primarily to prevent rectal toxicity from radiation therapy. We are seeing now that there may be other benefits,” Hankins explains in an interview with Targeted Oncology^TM.

The study utilized a massive dataset drawn from Medicare and included 247,250 patients with prostate cancer who received radiation therapy between 2015 to 2022. Rather than focusing on individual patient-level data, the team opted for a county-level approach to maximize the reach and scale of the study.

“These are large data sets that are readily available, so this is based on diagnoses that are reported, or really government-reported diagnosis codes, and so we can dive into large data sets to see if we can find associations with improvement in these [adverse events],” he shares.

The analysis revealed a notable association: counties with higher utilization of rectal spacers during prostate cancer radiotherapy showed lower rates of ED diagnoses. While the data is observational and further research is needed to confirm causality, the findings point toward a potentially broader protective role for rectal spacers.

REFERENCE:

Hankins RA, Sato R, Mehta P, Bhattacharyya S, Ezekwekwu E, Collins S. Real-world U.S. county-level analysis of erectile dysfunction diagnosis following radiation therapy for localized prostate cancer: The impact of rectal spacer utilization. J Urol. 2025;213(5S):e1327. doi:10.1097/01.JU.0001110184.48142.9e.03