The female sex hormone oestrogen has an anti-viral effect against the influenza A virus - otherwise known as the flu - scientists have found, which might explain why men often appear to be hit harder by the symptoms when infected.
When a team from Johns Hopkins University exposed male and female nasal cells - which are most severely affected by influenza A - to oestrogen compounds and the flu, they found that the oestrogen actively slowed down replication of the virus in cells from women but not men.
For years, scientists have been gathering evidence of oestrogen’s protective qualities, with past studies finding that estradiol - a type of oestrogen - and various oestrogenic chemicals have anti-viral effects on several very serious viruses, including HIV, Hepatitis C, Ebola, and human cytomegalovirus (HCMV).
The protective mechanism appears to block the ability of these viruses to replicate in human cells, and because swift replication is key to how the influenza A virus is able to achieve such acute infections in humans, the Johns Hopkins team decided to test the effects of various oestrogen compounds on it.
Gathering human nasal epithelial cell (hNEC) cultures from 10 male and 42 female donors between 18 and 45 years old, the team exposed them to a type of oestrogen called endogenous 17β-estradiol (E2) and a class of drugs called select oestrogen receptor modulators (SERMs), which are often used in hormone therapy treatments to activate cell receptors that produce oestrogen-like effects.
They then infected these cultures with a seasonal influenza A virus to figure out if oestrogenic signalling would affect how the infection spread, and if the effects differed between male and female cells.
The researchers found that while the SERM drugs and oestrogen weren’t very effective against the virus if introduced after the cells were infected, if the cells were injected with SERMs and oestrogen between 72 and 24 hours before infection, they showed greater resistance against the influenza virus.
Interestingly, the female nasal cells were found to contain far less of the flu virus at the end of this process than the male cells, which suggests that the activity of these oestrogenic chemicals is sex-dependent.
"Other studies have shown that oestrogens have antiviral properties against HIV, Ebola and hepatitis viruses," said lead researcher, Sabra Klein. "What makes our study unique is two-fold. First, we conducted our study using primary cells directly isolated from patients, allowing us to directly identify the sex-specific effect of oestrogens."
"Second," she said, "this is the first study to identify the oestrogen receptor responsible for the antiviral effects of oestrogens, bringing us closer to understanding the mechanisms mediating this conserved antiviral effect of oestrogens."
Publishing their results in the American Journal of Physiology - Lung Cellular and Molecular Physiology (preprint), Klein and her team suggest that the oestrogenic chemicals they used in their study interacted with a protein structure called oestrogen receptor beta in the female nasal cells - a receptor that binds with other molecules to prompt an immune response.
A better understanding of the mechanism behind oestrogen’s apparent protective qualities could be the key to reducing the severity of the flu and its ability to spread between people, they say.
The next step is to study the fluctuating oestrogen levels that cycle through pre-menopausal women and those taking specific types of birth control or undergoing hormone treatments to figure out how to manipulate this anti-viral effect in future medical treatments.
"[P]re-menopausal women on certain kinds of birth control or post-menopausal women on hormone replacement may be better protected during seasonal influenza epidemics," says Klein. "We see clinical potential in the finding that therapeutic oestrogens that are used for treating infertility and menopause may also protect against the flu."