title: Co-infection of respiratory bacterium with severe acute respiratory syndrome coronavirus induces an exacerbated pneumonia in mice.
abstract: SARS-CoV grows in a variety of tissues that express its receptor, although the mechanism for high replication in the lungs and severe respiratory illness is not well understood. We recently showed that elastase enhances SARS-CoV infection in cultured cells, which suggests that SARS development may be due to elastase-mediated, enhanced SARS-CoV infection in the lungs. To explore this possibility, we examined whether co-infection of mice with SARS-CoV and Pp, a low-pathogenic bacterium which elicits elastase production in the lungs, induces exacerbation of pneumonia. Mice co-infected with SARS-CoV and Pp developed severe respiratory disease with extensive weight loss, resulting in a 33~90% mortality rate. Mice with exacerbated pneumonia showed enhanced virus infection in the lungs and histopathological lesions similar to those found in human SARS cases. Intranasal administration of LPS, another elastase inducer, showed an effect similar to that of Pp infection. Thus, this study shows that exacerbated pneumonia in mice results from co-infection with SARS-CoV and a respiratory bacterium that induces elastase production in the lungs, suggesting a possible role for elastase in the exacerbation of pneumonia.
authors.affiliation: National Institute of Infectious Diseases, Murayama Branch, Musashi-Murayama, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ami
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shirato
authors.forename: Rie
authors.initials: R
authors.lastname: Watanabe
authors.forename: Naoko
authors.initials: N
authors.lastname: Iwata
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakagaki
authors.forename: Shuetsu
authors.initials: S
authors.lastname: Fukushi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saijo
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morikawa
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Taguchi
mesh_terms: D000818:Animals; D001835:Body Weight; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010196:Pancreatic Elastase / Q000096:biosynthesis*; D044142:Pasteurella pneumotropica / Q000201:enzymology* / Q000254:growth & development; D011024:Pneumonia, Viral / Q000473:pathology* / Q000503:physiopathology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000254:growth & development*; D045169:Severe Acute Respiratory Syndrome / Q000473:pathology* / Q000503:physiopathology*; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D010196:Pancreatic Elastase