Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge
| Autor: | Lance Price, Candice C. Clay, Kevin S. Harrod, Jesse Van Westrienen, Fletcher F. Hahn, Jennifer Knight, Nathan Donart, Ndingsa Fomukong, Wanli Lei |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
T-Lymphocytes
viruses Immunology Inflammation Antibodies Viral Severe Acute Respiratory Syndrome Virus Replication medicine.disease_cause Microbiology Monocytes Cell Line Proinflammatory cytokine Immune system Viral Envelope Proteins Immunity Virology Chlorocebus aethiops medicine Animals Humans Lung Coronavirus Membrane Glycoproteins biology Macrophages virus diseases Dendritic Cells Pneumonia Macrophage Activation respiratory system Immunoglobulin A respiratory tract diseases medicine.anatomical_structure Viral replication Immunoglobulin G Insect Science Spike Glycoprotein Coronavirus biology.protein Pathogenesis and Immunity Cytokines Antibody medicine.symptom |
| Zdroj: | Journal of Virology |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.06791-11 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|