The GPC is processed into three chains :
Stable Signal Peptide (SSP) Association of the SSP is essential for intracellular trafficking and proteolytic maturation of the GPC complex . The SSP interacts with the cytosolic domain of GP2 and is retained as part of the mature GPC .
Glycoprotein G1 (GP1)
Glycoprotein G2 (GP2) GP2 facilitates the virus's entry into host cells through pH-induced fusion of the viral and endosomal membranes .
Specific N-linked glycans on the arenavirus surface glycoprotein (GP) mask important epitopes and help the virus evade antibody responses . The N-linked glycosylation profiles of arenavirus glycoproteins are viable targets for designing attenuated viruses for vaccine development against arenavirus-associated illnesses . Glycans facilitate the virus to evade neutralizing antibodies .
The GPC complex is essential for the virus's infectivity . The stable signal peptide (SSP) plays a crucial role in intracellular trafficking and proteolytic maturation of the GPC complex . A charged residue in SSP, lysine 33, is specifically required for the fusion activity of the GPC complex .
The GPC is a key target for vaccine development against arenaviruses . Mutations within GPC can attenuate the virus and increase immunogenicity . Antibodies directed against the GPC can neutralize the virus by altering virion binding/fusion . Specific mutations acquired early during serial passaging attenuate visceral disease while not impacting the neurovirulence of the Junin virus .
Arenaviruses, including Junin virus, utilize the SKI-1/S1P protease for GPC processing, which is essential for virus growth in cell culture . The SKI-1/S1P protease mediates the major cleavage step for generating mature surface glycoproteins .
| Virus Clone | GPC Mutations | Visceral Disease | Neurovirulence | Attenuation |
|---|---|---|---|---|
| rRom | None | Lethal | Yes | No |
| rRom/GPC-R484G | R484G | Lethal | Yes | No |
| rRom/GPC-XJ13 | XJ13-specific | No | Yes | Partial |
| rRom/GPC-XJ44 | XJ44-specific | Delayed onset | Yes | Yes |
| rRom/GPC-T168A | T168A | Delayed onset | Yes | Yes |