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Review
. 2021 Dec;12(1):2060-2072.
doi: 10.1080/21505594.2021.1960106.

The pathogenesis and virulence of enterovirus-D68 infection

Syriam Sooksawasdi Na Ayudhya  1 , Brigitta M Laksono  1 , Debby van Riel  1
Affiliations
Review

The pathogenesis and virulence of enterovirus-D68 infection

Syriam Sooksawasdi Na Ayudhya et al. Virulence. 2021 Dec.

Abstract

In 2014, enterovirus D68 (EV-D68) emerged causing outbreaks of severe respiratory disease in children worldwide. In a subset of patients, EV-D68 infection was associated with the development of central nervous system (CNS) complications, including acute flaccid myelitis (AFM). Since then, the number of reported outbreaks has risen biennially, which emphasizes the need to unravel the systemic pathogenesis in humans. We present here a comprehensive review on the different stages of the pathogenesis of EV-D68 infection - infection in the respiratory tract, systemic dissemination and infection of the CNS - based on observations in humans as well as experimental in vitro and in vivo studies. This review highlights the knowledge gaps on the mechanisms of systemic dissemination, routes of entry into the CNS and mechanisms to induce AFM or other CNS complications, as well as the role of virus and host factors in the pathogenesis of EV-D68.

Keywords: Enterovirus D68; acute flaccid myelitis; central nervous system; enterovirus; neuroinvasion; pathogenesis; picornavirus; respiratory disease; systemic pathogenesis; viremia.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Hypothetical model of pathogenesis of EV-D68 infection based on findings from EV-D68 infected patients and experimental in vivo and in vitro studies. (a) EV-D68 infection in the respiratory tract: Inhaled virus particles firstly replicate in the upper respiratory tract and might spread to the lower respiratory tract. (b) EV-D68 infection outside the respiratory tract: Systemic dissemination of virus into the bloodstream and/or draining lymph nodes, resulting in viremia and infection of extra-respiratory tissues including the gastrointestinal tract, skin and heart. (c) EV-D68 infection in the CNS: EV-D68 may invade the CNS through infection of the muscles and subsequent spread via the neuromuscular junction to motor neurons in the anterior horn of the spinal cord using retrograde axonal transport. Other possible invasion mechanisms into the CNS are via the blood-brain barrier, blood-CSF barrier or cranial nerves. Purple dot represents EV-D68. Purple arrow represents the flow of EV-D68 systemic dissemination in the circulation
See this image and copyright information in PMC

References

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