Coronavirus infection of the central nervous system: host–virus stand-off

• Published in: Nature reviews. Microbiology 2006-02, Vol.4 (2), p.121-132
• Main Authors: Stohlman, Stephen A, Bergmann, Cornelia C, Lane, Thomas E
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Biomedical and Life Sciences; Central nervous system; Central Nervous System Diseases - immunology; Central Nervous System Diseases - virology; Chronic illnesses; Coronavirus; Coronavirus Infections - immunology; Coronavirus Infections - virology; Coronaviruses; COVID-19; Disease; Encephalomyelitis; Hepatitis; Immune response; Immunity, Innate - immunology; Immunology; Infections; Infectious Diseases; Life Sciences; Lymphocytes; Mammals; Medical Microbiology; Mice; Microbiology; Murine hepatitis virus - immunology; Murine hepatitis virus - pathogenicity; Murine hepatitis virus - physiology; Nervous system; Parasitology; Pathogenesis; Pathogens; Pathology; Proteins; review-article; T-Lymphocytes - immunology; T-Lymphocytes - virology; Viral infections; Virology; Virus Replication; Viruses
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro1343

The need for a balance between pathogen elimination and protection from cellular damage means that the central nervous system (CNS) is a partially protected niche that some pathogens can exploit. Here, the authors discuss the immune regulation of acute and persistent CNS infection by coronaviruses, using mouse hepatitis virus as a model. Key Points Coronaviruses infect humans, rodents and several agriculturally important animals. Mouse hepatitis virus (MHV) causes acute infections of the murine liver and lungs and persistent infections of the gastrointestinal tract and central nervous system (CNS). Interactions of immune effectors and cells of the CNS can be studied using a non-lethal gliatropic strain of MHV. This model sheds light on the interplay of cytokines, chemokines and innate and adaptive immune effectors during acute infection, as well as their role in regulating coronavirus persistence. This review summarizes data that show how distinct phases of CNS infection are associated with the induction of innate danger signals, altered patterns of inflammatory cells and expression of antiviral effector functions. This leads to a state of virus–host coexistence that is beneficial to the survival of both. During acute infection, the principal antiviral effectors are virus-specific T cells, which use distinct mechanisms to control virus replication in a CNS-cell-type specific manner. Control of viral replication in CNS-resident macrophages (microglia) and astrocytes is dependent on CD8 + T-cell perforin-mediated cytolysis. By contrast, control of replication in oligodendrocytes requires secretion of the soluble mediator, interferon-γ. Control of virus replication is accompanied by downregulation of CD8 + T-cell cytolytic function and recruitment of virus-specific antibody-secreting cells into the CNS. Maintenance of local secretion of neutralizing antibody is crucial in preventing the re-emergence of infectious virus, indicating that virus persists in a replication-competent form. In the MHV model, the limitation of prolonged cytolytic activity sustains CNS function, while soluble mediators control, but cannot eradicate, persistent infection. Several viruses infect the mammalian central nervous system (CNS), some with devastating consequences, others resulting in chronic or persistent infections associated with little or no overt pathology. Coronavirus infection of the murine CNS illustrates the contributions of both the innate immune response and specific