Recent advances on the role of host factors during non-poliovirus enteroviral infections

Abstract

Non-polio enteroviruses are emerging viruses known to cause outbreaks of polio-like infections in different parts of the world with several cases already reported in Asia Pacific, Europe and in United States of America. These outbreaks normally result in overstretching of health facilities as well as death in children under the age of five. Most of these infections are usually self-limiting except for the neurological complications associated with human enterovirus A 71 (EV-A71). The infection dynamics of these viruses have not been fully understood, with most inferences made from previous studies conducted with poliovirus. Non-poliovirus enteroviral infections are responsible for major outbreaks of hand, foot and mouth disease (HFMD) often associated with neurological complications and severe respiratory diseases. The myriad of disease presentations observed so far in children calls for an urgent need to fully elucidate the replication processes of these viruses. There are concerted efforts from different research groups to fully map out the role of human host factors in the replication cycle of these viral infections. Understanding the interaction between viral proteins and human host factors will unravel important insights on the lifecycle of this groups of viruses. This review provides the latest update on the interplay between human host factors/processes and non-polio enteroviruses (NPEV). We focus on the interactions involved in viral attachment, entry, internalization, uncoating, replication, virion assembly and eventual egress of the NPEV from the infected cells. We emphasize on the virus- human host interplay and highlight existing knowledge gaps that needs further studies. Understanding the NPEV-human host factors interactions will be key in the design and development of vaccines as well as antivirals against enteroviral infections. Dissecting the role of human host factors during NPEV infection cycle will provide a clear picture of how NPEVs usurp the human cellular processes to establish an efficient infection. This will be a boost to the drug and vaccine development against enteroviruses which will be key in control and eventual elimination of the viral infections.

Enterovirus genomic load and disease severity among children hospitalised with hand, foot and mouth disease

“…Immunopathological injury also affects the cardiopulmonary system [5] . There are yet no effective antiviral drugs targeting HFMD associated enteroviruses, although significant efforts have been made to understand virus-human host interactions in order to identify promising candidates [6] . The role of viral load in the progress of HFMD and development of complications is of significance to both clinicians and researchers alike.…”

Nonpolio Enterovirus Activity during the COVID-19 Pandemic, Taiwan, 2020

“…The strict compliance with nonpharmaceutical interventions implemented during the coronavirus disease (COVID-19) pandemic has been associated with a decline in influenza activity in many countries, including Taiwan (1)(2)(3)(4). Handwashing, disinfecting frequently touched surfaces, and closure of schools might also be effective against nonpolio enteroviruses (NPEV), which commonly cause a spectrum of illnesses in young populations in Asia (5). We observed lower NPEV activity during the 2019-20 season in Taiwan compared with the average of the 5 previous seasons, which might be attributable to strict compliance with nonpharmaceutical interventions.…”

Molecular Pathogenicity of Enteroviruses Causing Neurological Disease

“…Another EV-A71 receptor called human P-selectin glycoprotein ligand-1 (PSGL-1) is expressed primarily on leukocytes and is bound by select EV-A71 strains . Additional attachment molecules that enhance viral infectivity and contribute to viral dissemination and neurotropism include heparan sulfate glycosaminoglycans (HS) (Tan et al, 2013), sialic acid (Yang et al, 2009), annexin II (Yang et al, 2011), nucleolin (Su et al, 2015), vimentin (Du et al, 2014) and heat shock protein 70 (Xu et al, 2019) among others (reviewed in Owino and Chu, 2019). Other receptors utilized by enteroviruses for cell entry that may contribute to neuropathogenicity include the decay-accelerating factor (DAF or CD55, part of the complement cascade) used by CVA21, echovirus 6 and echovirus 11 (Shafren et al, 1997;Lea et al, 1998;Renois et al, 2011) or Coxsackievirus and Adenovirus Receptor (CAR), which is the main entry receptor for Coxsackie B viruses (Martino et al, 2000).…”

“…Viral entry and replication rely heavily on numerous host factors and are fundamental processes dictating the success of a viral infection (Figure 1). Many studies have identified host factors that are critical for EV propagation (reviewed in Owino and Chu, 2019). However, much of this work was performed on nonneuronal cell types which have shown little overlap between the deregulated host proteins identified during EV infected motor neurons (Too et al, 2018), reinforcing the need to verify the role of these host factors in CNS relevant models.…”