Coxsackievirus

Coxsackievirus belongs to the family MicroRNA Viruses and the genus Enterovirus. It can be divided into two groups: Group A, which contains 23 serotypes. and Group B, covering 6 serotypes. The virus is in the form of icosahedral spherical particles with a diameter of approximately 23 to 30 nanometers. The virus is composed of nucleic acid and proteins, with an exposed nucleocapsid and no envelope covering it. The Coxsackievirus was first discovered in fecal samples by Dr. Gilbert Dalldorf and his colleagues in 1948 while searching for a cure for poliomyelitis, and was named after its discovery in the small town of Coxsackiewicz, New York.

Introductions

Coxsackievirus is a common virus that infects the human body through the respiratory and digestive tracts. After virus infection, it can cause upper respiratory tract infections, acute myocarditis, and other diseases, posing a serious threat to the health of infants and young children. In general, infants and young children often have latent infections. And for children under 5 years old, especially those under 3 years old, detoxification can take up to a month. Coxsackievirus has strong infectivity, and its main transmission routes include gastrointestinal fecal oral transmission, respiratory secretions transmission, and transmission through contact with infected hands, daily objects, and food. Therefore, it is highly susceptible to spread in collective units. This virus is spreading globally, with significantly higher infection rates in developing countries. The virus can be prevalent in all seasons, but the peak season is summer and autumn.

Pathogenicity

The pathogenic process of Coxsackievirus begins with its initiation of infection by binding to specific receptors on the surface of host cells. The Coxsackievirus adenovirus receptor (CAR) is a key receptor for most Group B Coxsackievirus (CVB) and some Group A serotypes, while the decay accelerating factor (DAF, also known as CD55) acts as a co receptor to enhance virus binding and invasion ability. After receptor binding, the viral capsid protein (especially VP1) undergoes conformational changes, promoting the release of RNA genome into the host cell cytoplasm and initiating replication; After entering the cell, viral RNA serves as a template to translate and generate a single polyprotein. This polyprotein is cleaved by viral proteases (3Cpro and 2Apro) into structural proteins (VP1-VP4) and non-structural proteins (such as RNA dependent RNA polymerase 3Dpol, helicase 2C, etc.). At the same time, the virus hijacks the host ribosome and inhibits host mRNA translation through 2Apro mediated eukaryotic initiation factor eIF4G cleavage. It also interferes with cellular processes such as vesicle transport and autophagy, providing support for its own proliferation.

Figure 2. Real time PCR of Coxsackievirus B.

Clinical Manifestations

Human infection with Coxsackievirus can easily cause changes such as herpetic pharyngitis and non-paralyzing poliomyelitis. The clinical manifestations are complex and diverse, including aseptic meningitis, encephalitis, myocarditis, pericarditis, epidemic chest pain, herpetic pharyngitis, etc. Some conditions are similar to poliomyelitis.

Infected individuals may experience cold symptoms such as fever, sneezing, and coughing. Pregnancy infection can cause non paralyzing poliomyelitis lesions and lead to intrauterine infection and teratogenicity of the fetus. Coxsackievirus can cause meningitis and mild paralysis, pleural pain, intercostal pain, Hispania, respiratory diseases, conjunctivitis, and hand foot mouth syndrome. Many patients with hand, foot and mouth disease are associated with Coxsackievirus Group A 16 infection, which is an important cause of outbreaks and transmission of hand, foot and mouth disease. Other Coxsackievirus groups such as CoxA4, CoxA5, CoxA9, CoxA10, and CoxB5 can also cause hand, foot, and mouth disease.

Clinical Manifestations	Details
Coxsackievirus type A infection	Coxsackievirus type A infection is more common in children and 21.7% in adults. The incubation period is 1-3 days, and upper respiratory tract infection occurs. The onset is sudden, with runny nose, cough, sore throat, fever, and overall discomfort. The rash can be herpes and papules, mainly distributed on the peripheral side of the trunk, back, and back of the limbs, showing a centrifugal distribution, especially on the face, fingers, toes, and back. Therefore, it is called the triad of hand, foot, and mouth.
Coxsackievirus type B infection	Causing characteristic infectious chest and rib pain disease. May be combined with meningitis, myocarditis, fever, Guillain Barr é syndrome, hepatitis, hemolytic anemia, and pneumonia. Part of the Coxsackievirus can establish persistent infection in host cells by inhibiting antiviral signals (such as 3Cpro mediated IRF3 cleavage to suppress interferon alpha/beta production) or hiding in immune exempt sites (such as heart tissue) to evade immune clearance. Persistent infection is closely related to chronic diseases such as dilated cardiomyopathy, type 1 diabetes (related to pancreatic beta cell injury induced by Coxsackie virus B) and chronic fatigue syndrome.

Treatment Options

At present, there is a lack of specific treatment, and general and supportive therapies should be emphasized. Ribavirin or interferon can be tried. The progression of neonatal myocarditis is rapid, and oxygen should be given and quietness should be maintained. When heart failure occurs, rapid digitalis therapy should be used early. Administer appropriate antibiotics to prevent secondary bacterial infections. Sedatives or procaine local blockade should be given to patients with convulsions and severe muscle pain. Anesthetics such as morphine and pethidine should not be used easily. Corticosteroids can be considered for use in patients with myocarditis accompanied by heart failure, cardiogenic shock, severe arrhythmias (such as high atrioventricular block, sick sinus syndrome, etc.), and pericarditis, and are expected to achieve certain results. Given that this hormone can suppress the body's immune function and facilitate virus replication, it is not recommended to use it in general cases

Anti-Coxsackievirus Antibodies

Coxsackievirus Antigens