Journal article
Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection
Journal of immunology (Baltimore, Md. : 1950), Vol.198(10), pp.4046-4053
05/15/2017
DOI: 10.4049/jimmunol.1601896
PMCID: PMC5450662
PMID: 28373583
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.
Details
- Title: Subtitle
- Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection
- Creators
- Rudragouda Channappanavar - Department of Microbiology, University of Iowa, Iowa City, IA 52242Craig Fett - Department of Microbiology, University of Iowa, Iowa City, IA 52242Matthias Mack - Department of Internal Medicine, University Hospital Regensburg, Regensburg 93042, GermanyPatrick P Ten Eyck - Institute for Clinical and Translational Science, University of Iowa, Iowa City, IA 52242; andDavid K Meyerholz - Department of Pathology, University of Iowa, Iowa City, IA 52242Stanley Perlman - Department of Microbiology, University of Iowa, Iowa City, IA 52242; stanley-perlman@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Journal of immunology (Baltimore, Md. : 1950), Vol.198(10), pp.4046-4053
- DOI
- 10.4049/jimmunol.1601896
- PMID
- 28373583
- PMCID
- PMC5450662
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- United States
- Grant note
- P01 AI060699 / NIAID NIH HHS R01 AI129269 / NIAID NIH HHS R01 AI091322 / NIAID NIH HHS
- Language
- English
- Date published
- 05/15/2017
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Biostatistics; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777470202771
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