Role of breast cell infection in flu transmission between mothers and breast-feeding ferrets

October 8, 2015, Public Library of Science
A ferret mother with her kits. Credit: Jeff Coombs

Influenza is known as an infectious respiratory disease, but a study published on October 8th in PLOS Pathogens suggests that infected cells in breast tissues could play a role in virus transmission from mothers to breast-feeding infants and vice versa using a ferret model.

Alyson Kelvin, from the University Health Network, Toronto, Canada, and colleagues developed a novel infant-mother ferret model utilizing nursing mother ferrets and their 4-week-old infants to investigate the host-pathogen interactions of infection between and breast-feeding infants. Ferrets are known to be infected by human flu viruses, and can transmit the from ferret-to-ferret in a fashion that is believed to mimic the human situation.

Initially, the researchers infected either mothers or infants through nasal inoculation with the 2009 H1N1 strain of influenza virus and closely followed the health of both animals. When the infants were exposed, both they and—a few days later—their mothers developed influenza with symptoms in both upper and lower respiratory tracts. Similarly, when mothers were exposed to the virus, first they and subsequently their nursing young became ill with influenza, again involving upper and lower respiratory tracts.

As mammary glands are a significant point of contact between mothers and infants, the researchers then investigated the susceptibility of cells in mammary glands to influenza infection and the breast tissue as a possible source of virus transmission. They examined virus presence within mammary tissue as well as virus in the mother's milk.

All ferret mothers tested had at least one that contained infectious influenza virus. Live influenza virus was present in the nipples of positive mammary glands, and was also found in the milk of mothers of inoculated infants. This shows that mammary glands are able to harbor live influenza virus, and that live virus can be shed into the milk of secondarily infected mothers.

When the researchers directly inoculated the ferret mammary gland, they found that its cells could be directly infected by influenza virus and then were able to produce live virus. Infants nursed by these mothers became infected themselves, likely through the breast because the transmitted virus was found in the infants before it was detectable in nasal liquid from the mothers. However, transmission through direct contact of infected mothers or infected infants through a non-breast feeding route cannot be ruled out. Just like virus transmitted from the mother's respiratory tract, transmission that appeared to occur through the mammary gland led to severe disease and mortality in the ferret infants.

Although the researchers then showed that isolated human mammary cells can also be directly infected by the flu virus, this by no means proves that human breast tissue becomes infected during influenza infection. Comparing gene expression patterns in infected ferret mammary cells with uninfected ones, they saw substantial changes that suggest that besides eliciting an immune response, influenza infection of mammary gland cells shuts off milk production genes and activates genes involved in cell proliferation and growth.

Looking at whole mammary glands from ferrets, the researchers also saw changes indicating the cessation of milk production, but it still remains to be determined whether the changes seen in cultured human cells have any effects on milk production or on breast tissue in flu-infected people. For instance, it is well documented that ferrets are more susceptible to influenza H5N1 virus systemic than humans, and therefore it is still possible that spreading of the virus to mammary cells is a ferret-specific event not seen in humans. In any case, the present study emphasizes that we know little about influenza transmission, and that more studies are needed in humans and in animal models to understand how the virus moves from host to host.

Referring to data that Middle-Eastern Respiratory Syndrome (MERS) virus might be transmitted to humans from camel milk, the researchers say, together with their findings "support a hypothesis that respiratory viruses may have the ability to also infect mammary tissue, including human breast cells, possibly due to a shared branched architecture and cellular structure of epithelial cells in lungs and mammary glands".

Regarding the public health implications, they emphasize that their data "reinforce the importance of seasonal influenza vaccination in pregnant and breastfeeding women". Because current guidelines focus on respiratory transmission, they also suggest that "further investigation and guideline development for the management of influenza transmission between mothers and infants may be important."

Explore further: Team finds role for soft palate in adaptation of transmissible influenza viruses

More information: Paquette SG, Banner D, Huang SSH, Almansa R, Leon A, Xu L, et al. (2015) Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses. PLoS Pathog 11(10): e1005173. DOI: 10.1371/journal.ppat.1005173

Related Stories

Team finds role for soft palate in adaptation of transmissible influenza viruses

September 23, 2015
National Institutes of Health scientists and their colleagues identified a previously unappreciated role for the soft palate during research to better understand how influenza (flu) viruses acquire the ability to move efficiently ...

Ferrets, pigs susceptible to H7N9 avian influenza virus

May 23, 2013
Chinese and U.S. scientists have used virus isolated from a person who died from H7N9 avian influenza infection to determine whether the virus could infect and be transmitted between ferrets. Ferrets are often used as a mammalian ...

Virus in cattle linked to human breast cancer

September 15, 2015
A new study by University of California, Berkeley, researchers establishes for the first time a link between infection with the bovine leukemia virus and human breast cancer.

Evolution of equine influenza led to canine offshoot which could mix with human influenza

June 19, 2014
Equine influenza viruses from the early 2000s can easily infect the respiratory tracts of dogs, while those from the 1960s are only barely able to, according to research published ahead of print in the Journal of Virology. ...

Researchers ferret out a flu clue

December 18, 2014
Research that provides a new understanding as to why ferrets are similar to humans is set to have major implications for the development of novel drugs and treatment strategies.

Study puts troubling traits of H7N9 avian flu virus on display

July 10, 2013
The emerging H7N9 avian influenza virus responsible for at least 37 deaths in China has qualities that could potentially spark a global outbreak of flu, according to a new study published today (July 10, 2013) in the journal ...

Recommended for you

Onions could hold key to fighting antibiotic resistance

January 22, 2018
A type of onion could help the fight against antibiotic resistance in cases of tuberculosis, a UCL and Birkbeck-led study suggests.

New long-acting approach for malaria therapy developed

January 22, 2018
A new study, published in Nature Communications, conducted by the University of Liverpool and the Johns Hopkins University School of Medicine highlights a new 'long acting' medicine for the prevention of malaria.

Virus shown to be likely cause of mystery polio-like illness

January 22, 2018
A major review by UNSW researchers has identified strong evidence that a virus called Enterovirus D68 is the cause of a mystery polio-like illness that has paralysed children in the US, Canada and Europe.

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Flu may be spread just by breathing, new study shows; coughing and sneezing not required

January 18, 2018
It is easier to spread the influenza virus (flu) than previously thought, according to a new University of Maryland-led study released today. People commonly believe that they can catch the flu by exposure to droplets from ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.