Tissue tropism, pathology and pathogenesis of enterovirus infection

Abstract

Enteroviruses are very common and cause infections with a diverse array of clinical features. Enteroviruses are most frequently considered by practising pathologists in cases of aseptic meningitis, encephalitis, myocarditis and disseminated infections in neonates and infants. Congenital infections have been reported and transplacental transmission is thought to occur. Although skin biopsies during hand, foot and mouth disease are infrequently obtained, characteristic dermatopathological findings can be seen. Enteroviruses have been implicated in lower respiratory tract infections. This review highlights histopathological features of enterovirus infection and discusses diagnostic modalities for formalin-fixed paraffin-embedded tissues and their associated pitfalls. Immunohistochemistry can detect enterovirus antigen within cells of affected tissues; however, assays can be non-specific and detect other viruses. Molecular methods are increasingly relied upon but, due to the high frequency of asymptomatic enteroviral infections, clinical-pathological correlation is needed to determine significance. Of note, diagnostic assays on central nervous system or cardiac tissues from immunocompetent patients with prolonged disease courses are most often negative. Histopathological, immunohistochemical and molecular studies performed on clinical specimens also provide insight into enteroviral tissue tropism and pathogenesis.

Analysis of an echovirus 18 outbreak in Thuringia, Germany: insights into the molecular epidemiology and evolution of several enterovirus species B members

“…Headache, low-grade fever, nuchal rigidity and vomiting were the most prominent symptoms while rash or diarrhoea occurred in 5-6 % of patients [13]. Noteworthily, also severe and disseminated courses with a sepsis-like picture have been observed particularly in immunocompromised patients and neonates [14][15][16]. Recently, a case of fatal E-18 encephalitis in an 18-month-old infant was reported [17].…”

Is a multivalent hand, foot, and mouth disease vaccine feasible?

“…Cell tropism and pathogenicity depend on these receptors and on cellular trans-acting factors. 97,98 EV-A71 and CV-A16 but not CV-A6 and CV-A10, use the ubiquitous human scavenger receptor class B member 2 (hSCARB2) and the leukocyte P-selectin glycoprotein ligand 1 (PSGL-1) to infect a wide variety of host cells. 99,100 hSCARB2 is capable of viral binding, uncoating and internalization.…”

“…[102][103][104][105] Both CV-B3 and CV-B5 use the decay accelerating factor (DAF/CD55) for primary attachment and the coxsackievirus and adenovirus receptor (CAR) as an internalization receptor. 98,106 CAR is an integral membrane protein localized to tight junctions highly expressed in developing brain and heart, and mediates CV-B3 and CV-B5 infection of cardiac myocytes as well as neural progenitor and stem cells leading to acute myocarditis and CNS involvement. [106][107][108] Echovirus 30, the most common cause of aseptic meningitis in young infants, binds to the heterodimeric vitronectin avb3 receptor controlling neural cell differentiation to induce productive infection of target cells and neuronal cell death through the activation of the TRIO-RhoA signaling pathway.…”

A Single Mutation in the VP1 of Enterovirus 71 Is Responsible for Increased Virulence and Neurotropism in Adult Interferon-Deficient Mice

“…Viral encephalomyelitis characterized by inflammation involving both the brain and spinal cord also occurs and consists of perivascular cuffing, edema, necrosis, microglial nodules, and neuronophagia (47). Neurons in the brainstem typically show intense antigen positivity in severe cases, as well (49).…”