Glu₃₃₃ in rabies virus glycoprotein is involved in virus attenuation through astrocyte infection and interferon responses.

ABSTRACT: 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 Arg₃₃₃, whereas the attenuated strain HEP-Flury (HEP) possesses Glu₃₃₃. To investigate the potential attenuation mechanism dependent on a single amino acid at G333, comparative analysis was performed between HEP and HEP³³³R mutant with Arg₃₃₃. 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 HEP³³³R 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 Glu₃₃₃ contributes to RABV attenuation by determining the ability of the virus to infect astrocytes and stimulate subsequent IFN responses.

SUBMITTER: Itakura Y 

PROVIDER: S-EPMC8983343 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature