H5N1 Avian Influenza: Broadened Viral Tropism, Contaminated Milk, and an Increased Zoonotic Risk

The H5N1 virus, long associated with birds, has reached a new stage in its evolution. By infecting dairy cattle and replicating in the mammary gland, it is altering its viral tropism and revealing a new mode of transmission via raw milk. Scientists are warning of an unprecedented and potentially dangerous development.  

H5N1 Is No Longer Just an Avian Virus

H5N1, a highly pathogenic avian influenza virus, has undergone a profound transformation since 2024. While it previously circulated mainly among wild birds and domestic birds, it has been identified in several herds of dairy cows in the United States, marking a major shift in its viral biology. For the first time, the virus has demonstrated the ability to infect a non-carnivorous mammal species—in this case, cattle.  

Viral tropism: a key to understanding its spread

At the heart of this evolution lies viral tropism—that is, a virus’s ability to infect specific cell types. A review published in July 2025 describes how the tropism of H5N1 varies depending on the avian species: in chickens, it invades the entire body via endothelial cells; in ducks, it targets epithelial and neurological tissues. But in cattle, researchers have identified a unique tropism: the virus establishes itself in the mammary gland without causing any notable respiratory problems. This mammary tropism is based on a remarkable biological fact: the alveolar cells of cows express both SA-α2,3 (avian affinity) and SA-α2,6 (human affinity) receptors, providing H5N1 with a dual entry point. This characteristic makes dairy cows particularly vulnerable and turns milk into a potential vector for cross-species transmission.  

Raw milk, a new viral reservoir

Studies conducted by the CDC, the National Institutes of Health (NIH), and several U.S. universities have revealed that milk from infected cows contains not only viral RNA but also viable, infectious viral particles. In mice, ingestion of this milk led to systemic infection. In ferrets, a preclinical model for human influenza, infection via nasal exposure was also observed, although transmission between individuals remains limited. Raw milk thus becomes an active biological vector, calling into question traditional models of H5N1 spread.  

First Human Cases and Cattle-to-Cattle Transmission

Three human cases were reported among farmworkers exposed to infected cattle, who developed conjunctivitis and mild flu-like symptoms. Although these cases were mild, they confirm that the virus can engage in cross-species transmission. At the same time, several outbreaks of direct transmission between cows have been documented, likely via contaminated milk or milking equipment. The virus thus spreads within dairy herds without requiring an avian vector.  

The Issue of Pasteurization

The FDA has conducted tests on commercially available pasteurized dairy products and has not detected the virus. However, laboratory experiments have shown that standard pasteurization may not be fully effective in cases of very high viral loads. Although commercially available milk remains safe, these findings call for heightened vigilance on affected farms, particularly regarding the production of raw milk intended for direct consumption.  

A Virus Undergoing Evolutionary Transition

Recent structural analyses and sequencing data show that bovine H5N1 retains a strong affinity for avian receptors, while acquiring a partial ability to bind to human receptors. This dual tropism, confirmed by cryo-electron microscopy, suggests that the virus is in a phase of evolutionary transition, as was observed prior to the 1957 and 1968 influenza pandemics. Human-to-human transmission has not yet been observed, but researchers believe the virus is approaching the critical threshold.  

Public Health Response and the “One Health” Approach

In light of these developments, the public health response must be swift and coordinated. On dairy farms, authorities recommend the systematic disinfection of milking equipment, the isolation of sick animals, milk screening, and restrictions on animal movement. At the global level, scientists are advocating for a “One Health” approach that integrates animal health, human health, and environmental health. The development of appropriate vaccines—particularly mRNA vaccines for susceptible species—real-time genomics surveillance, and international cooperation are all essential tools for anticipating a potential pandemic.  

Milk: A New Epidemiological Warning Sign

Milk, long viewed as a simple indicator of production, is now becoming a biological marker of viral emergence. Its contamination with H5N1 shows that the virus continues to push the boundaries of species, organs, and modes of transmission. Against a backdrop of multiple zoonoses, the case of H5N1 in cattle serves as a reminder of a fundamental truth: viruses adapt faster than our surveillance systems. And it is sometimes unexpected environments—such as a cow’s mammary glands—that reveal the gaps in our vigilance.