Coronavirus infection of the central nervous system: host–virus stand-off
The review titled “Coronavirus infection of the central nervous system: host–virus stand-off” delves into the interactions between coronaviruses and the central nervous system (CNS). It’s a comprehensive exploration of the immune responses and pathogenesis in the context of neurotropic viruses like Mouse Hepatitis Virus (MHV), particularly the John Howard Mueller (JHMV) strain.
Here’s a detailed summary:
- Context: The study examines how coronaviruses, like MHV, affect the mammalian CNS, leading to either devastating consequences or chronic infections with minimal pathology.
- Key Insight: The study highlights the role of innate and specific host effector mechanisms in controlling virus replication in the CNS, noting that non-lytic humoral immunity is key in suppressing the virus during persistence despite the T-cell-mediated control of acute infection.
CNS and Immune System Interactions
- CNS Vulnerability: The CNS’s complex cell types and intricate communication networks are highly specialized, making it vulnerable to microbial and physical injuries. The CNS’s limited immunological activity is due to factors like the absence of lymphatic drainage and minimal expression of major histocompatibility complex (MHC) molecules.
Immune Effector Mechanisms
- Contrasting Responses: Inflammatory responses in the CNS during infections are robust, contrasting with its normally quiescent state. These responses involve both non-specific and antigen-specific immune components that create long-lived immunological memory.
Focus on MHV and JHMV
- Virus-Host Interaction: MHV’s pathogenesis starts with its spike protein interacting with the CEACAM-1 cellular receptor. The study emphasizes how variations in the spike protein and other viral genes influence pathogenesis and cell tropism.
Inflammatory Response in CNS Infection
- Dynamic Immune Response: MHV infection in the CNS triggers a dynamic and coordinated expression of chemokines, MMPs, and cytokines. These factors promote BBB disruption and attract innate immune cells, leading to CNS inflammation and damage.
Role of Antiviral Molecules
- TNF-α and iNOS: Despite their role in other CNS viral infections, TNF-α and iNOS don’t play a significant role in the anti-MHV host response. This suggests distinct mechanisms of immune response against different CNS pathogens.
Adaptive Immune Response
- Virus Control: The adaptive immune response, particularly virus-specific CD8+ T cells, plays a crucial role in decreasing virus replication in various CNS cells. However, this response doesn’t fully eliminate the virus, leading to its persistence in the CNS despite the reduction of inflammatory cells.
Chemokine and Cytokine Dynamics
- Chemokine Expression: Chemokines like CXCL9, CXCL10, and CCL5, expressed during the adaptive immune response, are crucial for attracting NK and T cells to the CNS. These chemokines play a vital role in controlling MHV infection and neuroinflammation.
Humoral Immunity and Virus Control
- Antibody Role: While serum antibodies provide protection against MHV, they don’t necessarily inhibit virus replication. The study highlights that control of acute MHV infection is largely independent of humoral immunity, but antibody presence is crucial for preventing the re-emergence of the virus post-infection.
This review sheds light on the complex interactions between neurotropic coronaviruses and the CNS’s immune mechanisms. It emphasizes the intricate balance between immune responses necessary to control infection and the need to prevent damage to the CNS. The persistence of viruses like MHV in the CNS, despite robust immune responses, underlines the challenges in fully understanding and treating CNS infections caused by coronaviruses.
Read More: https://www.nature.com/articles/nrmicro1343