Cheese made from contaminated raw milk was found to contain infectious avian influenza virus, raising potential health concerns for consumers, according to new research. The study also found that no virus was detected in samples of raw milk cheese with high acidity. Feta cheese, which is naturally more acidic, served as an example of this safer variety.

The findings were published on October 8 in Nature Medicine.

Tracking How the H5N1 Virus Behaves in Cheese

"In this study, we were specifically looking at the stability or persistence of highly pathogenic avian influenza H5N1 in raw milk cheese products," said senior author Diego Diel, professor of virology in the Department of Population Medicine and Diagnostic Sciences and director of the Virology Laboratory at the Animal Health Diagnostic Center (AHDC), all in the College of Veterinary Medicine (CVM).

"This research was initiated due to previous work demonstrating high levels of virus shedding in milk from infected cows and the fact that we have previously shown that the virus survives in refrigerated raw milk for extended periods of time," he said.

Virus Survived Twice as Long as Expected

Under Food and Drug Administration guidelines, raw milk cheese must be aged for at least 60 days at or above 35 degrees Fahrenheit. This process helps reduce moisture and destroy harmful bacteria that may be present in unpasteurized milk. However, the researchers detected infectious H5N1 virus after 120 days of aging at 39 degrees Fahrenheit, suggesting that the standard aging period may not fully eliminate viral contamination.

Acidity Plays a Key Role in Cheese Safety

A pH level below 7 is considered acidic. Most cheeses have a pH between 5.4 (as in cheddar) and 7 (as in camembert). Some, like feta, can be as low as 4.6 or even lower.

When the pH of raw milk cheese was between 5.8 and 6.6, the virus remained viable. No virus was detected in cheeses with a pH of 5 or below. The results highlight acidity as a key factor in inactivating the pathogen during cheesemaking.

Reducing Contamination Risks

According to Diel, steps to prevent contamination could include testing milk before cheesemaking and using only virus-free milk. Another option is to heat milk to sub-pasteurization temperatures, which could inactivate the virus while maintaining the raw milk cheese characteristics valued by artisanal producers.

Nicole Martin, study co-author and assistant research professor in dairy foods microbiology, emphasized the importance of this work: "The work we've done on H5N1 is critical to providing practical, timely, data-driven knowledge and recommendations to the dairy industry in the face of this outbreak that has affected a large proportion of the milk supply in the U.S., and it allows raw milk cheese makers to reduce risk."

Animal Tests Shed Light on Transmission

The study also included an animal experiment using ferrets, which are highly susceptible to H5N1. The animals were fed contaminated raw milk and raw milk cheese from the study. Some ferrets that drank the raw milk became infected, but those that ate the raw milk cheese did not.

Diel suggested that the difference may relate to how the virus interacts with the body. The fluid consistency of milk may allow the virus to make greater contact with mucous membranes in the throat, while cheese likely provides less exposure time for infection to begin.

Testing Cheese Samples for the Virus

To further examine virus stability, the team created small 5-gram experimental cheeses in the lab using raw milk spiked with H5N1. They also analyzed commercial cheese samples submitted to Cornell by FDA officials who suspected contamination.

"All four samples of company-made cheddar that we received tested positive for H5N1," Diel said.

Understanding How Acidity Is Created

Cheese becomes acidic either through direct acidification or by adding lactic acid-producing bacteria that convert milk sugars into lactic acid. "This acid drops the pH of the milk and depending on how far this fermentation is allowed to proceed determines how low the pH goes," Martin said.

The researchers used direct acidification in their experiments, adding lactic acid to H5N1-spiked milk to produce cheeses with varying levels of acidity for testing.

Research Collaboration and Support

Mohammed Nooruzzaman, an assistant research professor in the Department of Population Medicine and Diagnostic Sciences (CVM), is the paper's first author. Co-authors include postdoctoral associate Pablo Sebastian Britto de Oliveira; research associate Salman Butt; Samuel D. Alcaine, associate professor of food science (CALS); and Stephen Walker at the FDA's Office of Dairy and Seafood Safety.

The study was supported by the FDA and the New York State Department of Agriculture and Markets.

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By the time most people begin seeking help for multiple sclerosis (MS), the disease has already been quietly injuring the brain for years. Until recently, scientists were uncertain which cells were affected first or when the damage actually started.

Tracking the Disease's Earliest Attacks

Researchers at UC San Francisco have now provided the most detailed timeline yet by analyzing thousands of proteins circulating in the blood. Their findings show that the immune system begins attacking the brain's protective myelin sheath -- the fatty covering that insulates nerve fibers -- much earlier than scientists once believed.

The team measured fragments of myelin and other molecules left behind by immune attacks, along with the chemical signals that drive the immune system's response. This work allowed them to outline, for the first time, the chain of biological events that ultimately leads to the onset of MS.

The discovery opens the door to earlier diagnosis and, in the future, may make prevention possible.

The Body's Early Warning Signs

The research showed that MS first targets the myelin sheath. About a year later, evidence of damage to the underlying nerve fibers themselves begins to appear.

Among the immune-related proteins that rose during this initial stage, one stood out: IL-3. This molecule plays a central role in the early disease phase, when the central nervous system is already taking significant damage even though patients do not yet experience symptoms. IL-3 helps recruit immune cells into the brain and spinal cord, where they begin attacking nerve tissue.

"We think our work opens numerous opportunities for diagnosing, monitoring, and possibility treating MS," said Ahmed Abdelhak, MD, assistant professor of Neurology at UCSF, and the first and co-lead author of the paper, which was published in Nature Medicine on Oct. 20. "It could be a gamechanger for how we understand and manage this disease."

Following Blood Clues Years Before Diagnosis

The researchers analyzed more than 5,000 different proteins in blood samples from 134 individuals who eventually developed MS. These samples came from the U.S. Department of Defense Serum Repository, which stores blood from military applicants. Because the repository holds samples for decades, scientists were able to examine blood drawn years before these individuals were diagnosed.

Seven years prior to diagnosis, the researchers detected a spike in a protein known as MOG (myelin oligodendrocyte glycoprotein), which signals damage to the myelin insulation around nerve fibers. Roughly a year later, they observed a rise in neurofilament light chain, a marker of injury to the nerve fibers themselves.

During this same window, IL-3 and several related immune proteins appeared in the bloodstream, indicating that an immune assault was already underway.

Building the Foundation for a Predictive Blood Test

In total, the team identified about 50 proteins that could serve as early indicators of MS. They have since filed a patent application for a diagnostic blood test based on the 21 most reliable markers.

Ari Green, MD, chief of the Division of Neuroimmunology and Glial Biology in the UCSF Department of Neurology and senior author of the study, said the findings could reshape how doctors approach prevention and treatment.

"We now know that MS starts way earlier than the clinical onset, creating the real possibility that we could someday prevent MS -- or at least use our understanding to protect people from further injury."

Authors: Other UCSF authors are Gabriel Cerono, MD, Kiarra Ning, John Boscardin, PhD, The UCSF ORIGINS Study, Christian Cordano, MD, PhD, Asritha Tubati, Camille Fouassier, Eric D. Chow, PhD, Refujia Gomez, Adam Santaniello, Kelsey C. Zorn, MHS, Jill A. Hollenbach, PhD, MPH, Jorge R. Oksenberg, PhD, Bruce A.C. Cree, MD, PhD, MAS, Stephen L. Hauser, MD, Jonah R. Chan, PhD, Sergio E. Baranzini, PhD, Michael R. Wilson, MD, and Ari J. Green, MD. For all authors, see the paper.

Funding: This work was funded in part by the Department of Defense (HT94252310499), the National Institutes of Health (R01 NS105741 R01AG062562 R01AG038791, 1S10OD028511-01, R35NS111644, the Valhalla Foundation, the National MS Society, the Westridge Foundation, the National Multiple Sclerosis Society (RFA-2104-37504, SI-2001-35751), the Water Cove Charitable Foundation, Tim and Laura O'Shaughnessy, and the Littera Family. For all funding and disclosures, see the paper.

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