Furin-mediated protein processing in infectious diseases and cancer

Braun, Elisabeth; Sauter, Daniel

Like bacterial and viral exotoxins, most viral envelope glycoproteins need to be proteolytically cleaved before they can mediate viral entry into host cells. In many cases, viruses exploit cellular trypsin-or subtilisin-like endoproteases for this purpose. While subtilisin-like proteases such as furin require polybasic cleavage sites, trypsin-like proteases also recognise monobasic motifs and cleave after single arginine or lysine residues. 46 Notably, the dependency on specific proteases can also be an important determinant of tissue tropism and viral spread in an infected organism. For example, avirulent Newcastle disease virus (NDV) strains harbour a monobasic cleavage site in their Fusion (F) protein and result only in local infections (mainly in the respiratory tract) since expression of the respective host proteases is limited to a few cell types. In contrast, the F proteins of virulent NDV strains can be cleaved by furin or related proprotein convertases that are ubiquitously expressed. Consequently, these viruses are able to spread systemically and cause high rates of mortality in infected birds. 47 Another well-described example is the cleavage of influenza A virus hemagglutinin (HA). In contrast to low pathogenic avian influenza A viruses, their highly pathogenic counterparts harbour a polybasic furin cleavage site in the HA protein. 48 Thus, the ability of viruses to exploit furin may have drastic effects on their pathogenicity.