Glu 333 in rabies virus glycoprotein is involved in virus attenuation through astrocyte infection and interferon responses.

The amino acid residue at position 333 of the rabies virus (RABV) glycoprotein (G333) is a major determinant of RABV pathogenicity. Virulent RABV strains possess Arg ₃₃₃ , whereas the attenuated strain HEP-Flury (HEP) possesses Glu ₃₃₃ . To investigate the potential attenuation mechanism dependent on a single amino acid at G333, comparative analysis was performed between HEP and HEP ³³³ R mutant with Arg ₃₃₃ . We examined their respective tropism for astrocytes and the subsequent immune responses in astrocytes. Virus replication and subsequent interferon (IFN) responses in astrocytes infected with HEP were increased compared with HEP ³³³ R both in vitro and in vivo . Furthermore, involvement of IFN in the avirulency of HEP was demonstrated in IFN-receptor knockout mice. These results indicate that Glu ₃₃₃ contributes to RABV attenuation by determining the ability of the virus to infect astrocytes and stimulate subsequent IFN responses.
Competing Interests: The authors declare no competing interests.
(© 2022 The Author(s).)