Update of enterovirus 71 infection: epidemiology, pathogenesis and vaccine

Abstract

Enterovirus 71 (EV71) is a neurotropic human pathogen that is the causative agent of hand foot and mouth disease (HFMD), herpangina and brain stem encephalitis. Recurrent EV71 epidemics of various scales have occurred in the Asia-Pacific region. Several specific cell surface molecules serve as the receptors for EV71. Identification of the receptors is an important step to understand EV71 disease. Cytokines, lymphocytes and monocytes contribute significantly to EV71 pathogenesis. The interaction of EV71 and receptors may be associated with the cytokines immunopathogenesis. Some animal models have been established and aim to explore the pathogenesis of EV71 infections. EV71 antibodies can neutralize or enhance infection at subneutralizing levels. These results are important for EV71 vaccine and therapeutics design. Several clinical trials of human inactivated EV71 vaccine have recently been completed. The purpose of this review is to summarize recent discoveries about the epidemiology and pathogenesis of EV71 and provide insights into human vaccine development.

Keywords::

• brain stem encephalitis
• enterovirus 71
• hand foot and mouth disease
• receptor
• vaccine

Financial & competing interests disclosure

The authors thank the G.D. Hsiung Virology Laboratory at National Cheng Kung University Hospital for providing data. Our studies have been supported by grants from the National Science Council, Taiwan; the Multidisciplinary Center of Excellence for Clinical Trial and Research, Department of Health, Executive Yuan, Taiwan; and the Center of Infectious Disease and Signaling Research, National Cheng Kung University, Taiwan.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• B5 and C4 genotypes were the predominant strain of Enterovirus 71 (EV71) circulated in the Asia region recently.

• P-selectin glycoprotein ligand-1, scavenger receptor class B, member 2, Annexin II and heparan sulfate are identified as receptors for EV71 infection.

• Anti-IL-6 neutralizing antibodies therapy increased the survival rates and immune cell activation and reduced tissue damage in mice. It indicated the usefulness of IVIG treatment in severe EV71 infection.

• T cells, B cells and dendritic cell participated in EV71 infection and associated with disease severity and cytokine production.

• Several mouse models have been applied to EV71 infection by demonstrating neurological complications clinically and pathologically, however, failed to show pulmonary edema.

• Antibody-dependent enhancement of EV71 infectivity is proved by clinical implication, in vitro studies and animal studies.

• Phase I through Phase III clinical trials of inactivated EV71 vaccine had completed, some unresolved issues still leave behind.

Notes