Sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection

Rudragouda Channappanavar, Craig Fett, Matthias Mack, Patrick P. Ten Eyck, David K. Meyerholz, Stanley Perlman

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Pathogenic human coronaviruses (CoVs), such as the severe acute respiratory syndrome (SARS)-CoV and the Middle East respiratory syndrome-CoV, cause acute respiratory illness. Epidemiological data from the 2002-2003 SARS epidemic and recent Middle East respiratory syndrome outbreak indicate that there may be sex-dependent differences in disease outcomes. To investigate these differences, we infected male and female mice of different age groups with SARS-CoV and analyzed their susceptibility to the infection. Our results showed that male mice were more susceptible to SARS-CoV infection compared with age-matched females. The degree of sex bias to SARS-CoV infection increased with advancing age, such that middle-aged mice showed much more pronounced differences compared with young mice. Enhanced susceptibility of male mice to SARS-CoV was associated with elevated virus titers, enhanced vascular leakage, and alveolar edema. These changes were accompanied by increased accumulation of inflammatory monocyte macrophages and neutrophils in the lungs of male mice, and depletion of inflammatory monocyte macrophages partially protected these mice from lethal SARS. Moreover, the sex-specific differences were independent of T and B cell responses. Furthermore, ovariectomy or treating female mice with an estrogen receptor antagonist increased mortality, indicating a protective effect for estrogen receptor signaling in mice infected with SARS-CoV. Together, these data suggest that sex differences in the susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.

Original languageEnglish (US)
Pages (from-to)4046-4053
Number of pages8
JournalJournal of Immunology
Volume198
Issue number10
DOIs
StatePublished - May 15 2017

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Coronavirus Infections
Severe Acute Respiratory Syndrome
Sex Characteristics
Estrogen Receptors
Monocytes
Infection
Macrophages
Sexism
Coronavirus
Ovariectomy
Viral Load
Disease Outbreaks
Blood Vessels
Edema
Neutrophils
B-Lymphocytes
Age Groups

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection. / Channappanavar, Rudragouda; Fett, Craig; Mack, Matthias; Ten Eyck, Patrick P.; Meyerholz, David K.; Perlman, Stanley.

In: Journal of Immunology, Vol. 198, No. 10, 15.05.2017, p. 4046-4053.

Research output: Contribution to journalArticle

Channappanavar, Rudragouda ; Fett, Craig ; Mack, Matthias ; Ten Eyck, Patrick P. ; Meyerholz, David K. ; Perlman, Stanley. / Sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection. In: Journal of Immunology. 2017 ; Vol. 198, No. 10. pp. 4046-4053.
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