Table 1.

Histidine mutations that affect the flavivirus and alphavirus fusion mechanisms.

Mutation(s)	Locationa	Fusion phenotype	Proposed role(s) in fusion
Flavivirus (TBEV)
H248N b + H287A	DII: ij loopc close to fusion loop; in trimer groove DI: hinge, trimer interface	Fusion block	Trimer formation and stabilization
H323A	DIII: at interface with DI	Fusion block	pH sensor for dimer dissociation; trimer stabilization
Alphavirus (SFV)
H3A	DI: near linker region in trimer	pH shift, decreased fusion	Regulation of trimerization
H125A	DII: hinge, E1-E1 interface in virus glycoprotein shell	No significant phenotype	None
H230A	DII: ij loopc close to fusion loop; in trimer groove	Fusion block	Late step in fusion after trimer formation; no pH effect
H331A + H333A	DIII: at interface with DI	No significant phenotype	None

^aDomain location and position in prefusion conformation, unless indicated as trimer.

^bNote that H244 of DV (discussed in text) is analogous to H248 of TBEV.

^cThe ij loop is at the tip of DII, connecting β-strands i and j.