Estrogen compounds may decrease influenza A virus replication and help protect women from influenza, according to research recently published in the American Journal of Physiology: Lung Cellular and Molecular Physiology.
The severity of influenza can change during pregnancy, which suggests that sex steroid hormones like estrogens could be involved in virus replication, according to the researchers.
“Other studies have shown that estrogens have antiviral properties against HIV, Ebola and hepatitis viruses,” said lead investigator Sabra Klein, PhD, from Johns Hopkins University, in a prepared statement. “What makes our study unique is 2-fold. First, we conducted our study using primary cells directly isolated from patients, allowing us to directly identify the sex-specific effect of estrogens. Second, this is the first study to identify the estrogen receptor responsible for the antiviral effects of estrogens, bringing us closer to understanding the mechanisms mediating this conserved antiviral effect of estrogens.”
Dr Klein and her team collected human nasal epithelial cells from male and female donors to examine how estrogen affects the influenza virus’s ability to replicate. The researchers added the virus to the cell culture, along with estrogen (17β-estradiol), bisphenol A, and selective estrogen receptor modulators (SERM).
The results showed that 17β-estradiol, a SERM compound called raloxifene, and bisphenol A all reduced influenza virus replication in nasal cells from women. However, the virus replication was not reduced in the cells from men.
The researchers also observed that treatment with 17β-estradiol had no effect on interferon or chemokine secretion, but the estrogen significantly downregulated cell metabolic processes, including genes that encode zinc finger proteins, which contain estrogen response elements in their promoters.
The estrogen and SERMs only inhibited influenza A virus production at times post-low multiplicity of infection, and most of the antiviral effects were greater when the cell cultures were treated prior to the initiation of the infection. The authors of the study hypothesized that there may be a combination of host response and virus infection occurring synergistically to impair the replication at later periods of infection.
“Because estrogen levels cycle in premenopausal women, it may be difficult to see this protective effect in the general population,” Dr Klein noted. “But, premenopausal women on certain kinds of birth control or post-menopausal women on hormone replacement may be better protected during seasonal influenza epidemics. We see clinical potential in the finding that therapeutic estrogens that are used for treating infertility and menopause may also protect against the flu.”
1. Peretz J, Pekosz A, Lane AP, Klein SL. Estrogenic compounds reduce influenza A virus replication in primary human nasal epithelial cells derived from female, but not male, donors. Am J Physiol Lung Cell Mol Physiol. 2015; doi: 10.1152/ajplung.00398.2015.