Table 2 Reported virulence determinants

5′ UTR

158C

• Increases EV-A71 translation and virulence in mice

[81]

272G, 488 U, 700A/U

• Associates with higher prevalence in severe cases of EV-A71

[82]

VP1

31G

• Enhances EV-A71 entry into neuroblastoma

• Increases viral growth and fitness in human neuronal cells

• May facilitate CNS infection in humans

[83]

31D

• Enhances replication, infectivity, and fitness in colorectal cells

• Increases virion stability

[83]

L79R

• Confers advantage in viral binding ability and fitness in neuronal cells

• Potential determinant of host-adaptation and neurovirulence in humans

[84]

107A

• Regulates EV-A71 maturation via the efficient cleavage of VP0 precursor

• Increases viral uncoating efficiency

[85]

145

• Under positive selection

[45]

Q145E

• Enhances binding of EV-A71 to mouse neuroblastoma

• Increases viral binding and RNA accumulation of EV-A71

• Cooperates with VP2^K149M to increase mouse lethality in vivo

[86]

E145Q

• Observed in more severe cases

[87]

G145E

• Associates with increase in virulence in mice

[79], [80]

145Q/G, 244 K

• Associates with virus binding ability to PSGL-1

[88]

145G/Q/R, 164E

• Associates with higher prevalence in severe cases of EV-A71

[82]

145Q

• Key determinant of increased infectivity in human airway organoids

[89]

98 K, 104D

• Potential infectivity markers of human airway organoids

[89]

145E, 98 K/E

• Responsible for the development of viremia and neuropathogenesis, and increases levels of cytokines in Cynomolgus monkey model

[90]

K244E

• Associates with mouse adaptation and virulence

[91]

VP2

K149 M

• Increases RNA accumulation, viral toxicity, virulence, and uncoating in mouse neuronal cells

• Cooperates with VP1^Q145E to increase infectivity and mouse lethality of EV-A71, and increases cytotoxicity in Neuro-2a cells

[86]

2A

68 K

• Associates with higher prevalence in severe cases of EV-A71

[82]

3C

Region

• Can hamper the host innate defense by selectively blocking type I IFN synthesis

[92]

N69D

• Decreases viral replication and virulence in RD cells

• Regulates 3C^pro enzyme activity in mammalian cells

[93]

3D

I251T

• Contributes to a strong temperature sensitivity

• Decreases virulence in neonatal mice

[94]