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Table 2 Reported virulence determinants

From: Enterovirus A71: virulence, antigenicity, and genetic evolution over the years

Region Position/Factor Observations Ref
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
31D • Enhances replication, infectivity, and fitness in colorectal cells
• Increases virion stability
L79R • Confers advantage in viral binding ability and fitness in neuronal cells
• Potential determinant of host-adaptation and neurovirulence in humans
107A • Regulates EV-A71 maturation via the efficient cleavage of VP0 precursor
• Increases viral uncoating efficiency
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 VP2K149M to increase mouse lethality in vivo
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 VP1Q145E to increase infectivity and mouse lethality of EV-A71, and increases cytotoxicity in Neuro-2a cells
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 3Cpro enzyme activity in mammalian cells
3D I251T • Contributes to a strong temperature sensitivity
• Decreases virulence in neonatal mice