From the Guidelines
The pathogenesis of Coxsackievirus involves direct infection and damage to myocardial cells, leading to myocarditis, as well as immune-mediated damage and potential autoimmune responses. The virus, particularly group B, has a strong tropism for cardiac tissue, and its infection can result in active inflammatory destruction of myocytes, as seen in myocarditis [ 1 ].
Key Steps in Pathogenesis
- Initial entry through the gastrointestinal or respiratory tract
- Primary replication in local lymphoid tissues
- Viremia and dissemination to target organs, including the heart
- Direct infection and damage to myocardial cells, causing myocarditis
- Immune-mediated damage and potential autoimmune responses The virus attaches to host cells via specific receptors, enabling cell entry, and once inside, it releases its RNA genome, hijacks cellular machinery for replication, and produces viral proteins that eventually lead to cell lysis and release of new viral particles [ 1 ].
Clinical Implications
- Myocarditis can occur in patients with Coxsackievirus infection, particularly those with advanced disease
- The diagnosis of myocarditis should be based on established histological, immunological, and immunohistochemical criteria, with endomyocardial biopsy remaining the gold standard for definite diagnosis [ 1 ]
- Essential first-line tests to confirm the diagnosis include 12-lead ECG, transthoracic echocardiogram, and assessment of biomarker concentrations, including troponins [ 1 ]
From the Research
Pathogenesis of Coxsackievirus
The pathogenesis of Coxsackievirus (Coxsackie virus) involves several key aspects:
- Infection route: The route of infection can influence the morbidity and pathology of Coxsackievirus B (CVB) infections, with oral infection protecting the pancreas from damage but not from infection 2.
- Virus replication: Coxsackieviruses can persist for extended periods within certain host tissues, requiring evasion from the host immune response and a greatly reduced rate of replication 3.
- Tropism: CVs exhibit a unique tropism for progenitor cells in the host, which may help explain the susceptibility of young hosts to infection and the establishment of chronic disease in adults 3.
- Immune response: CVs can exploit autophagy to maximize viral replication and assist in unconventional release from target cells, and may acquire an envelope to provide resistance to neutralizing antibodies and efficient nonlytic viral spread 3.
- Organ involvement: Virus can be isolated from several organs, including the heart, spleen, and pancreas, indicating systemic infection 2.
Key Factors in Pathogenesis
Some key factors involved in the pathogenesis of Coxsackievirus include:
- Viral proteins: Such as VP1 and protein 3A, which can be detected in infected tissues 2.
- Host immune response: Including the production of alpha interferon (IFN-alpha), which may play a role in protecting the pancreas from damage 2.
- Autophagy: Which can be exploited by CVs to maximize viral replication and assist in unconventional release from target cells 3.
Disease Associations
Coxsackieviruses are associated with a range of diseases, including: