title: Primary severe acute respiratory syndrome coronavirus infection limits replication but not lung inflammation upon homologous rechallenge.
abstract: Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. Here, an African green monkey (AGM) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following SARS-CoV infection. During primary infection, SARS-CoV replicated in the AGM lung for up to 10 days. Interestingly, lung inflammation was more prevalent following viral clearance, as leukocyte numbers peaked at 14 days postinfection (dpi) and remained elevated at 28 dpi compared to those of mock-infected controls. Lung macrophages but not dendritic cells were rapidly activated, and both cell types had high activation marker expression at late infection time points. Lung proinflammatory cytokines were induced at 1 to 14 dpi, but most returned to baseline by 28 dpi except interleukin 12 (IL-12) and gamma interferon. In SARS-CoV homologous rechallenge studies, 11 of the 12 animals were free of replicating virus at day 5 after rechallenge. However, incidence and severity of lung inflammation was not reduced despite the limited viral replication upon rechallenge. Evaluating the role of antibodies in immune protection or potentiation revealed a progressive increase in anti-SARS-CoV antibodies in lung and serum that did not correlate temporally or spatially with enhanced viral replication. This study represents one of the first comprehensive analyses of lung immunity, including changes in leukocyte populations, lung-specific cytokines, and antibody responses following SARS-CoV rechallenge in AGMs.
authors.affiliation: Lovelace Respiratory Research Institute, Infectious Disease Program, Albuquerque, New Mexico, USA.
authors.forename: Candice
authors.initials: C
authors.lastname: Clay
authors.forename: Nathan
authors.initials: N
authors.lastname: Donart
authors.forename: Ndingsa
authors.initials: N
authors.lastname: Fomukong
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Knight
authors.forename: Wanli
authors.initials: W
authors.lastname: Lei
authors.forename: Lance
authors.initials: L
authors.lastname: Price
authors.forename: Fletcher
authors.initials: F
authors.lastname: Hahn
authors.forename: Jesse
authors.initials: J
authors.lastname: Van Westrienen
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Harrod
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D017934:Coronavirus / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D064370:Spike Glycoprotein, Coronavirus; D013601:T-Lymphocytes / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins