Endoproteolytic processing of the Ebola virus envelope glycoprotein: Cleavage is not required for function

Proteolytic processing is required for the activation of numerous viral gly coproteins. Here we show that the envelope glycoprotein from the Zaire stra in of Ebola virus (Ebo-GP) is proteolytically processed into two subunits, GP, and GP,, that are likely covalently associated through a disulfide link age, Murine leukemia virions pseudotyped with Ebo-GP contain almost exclusi vely processed glycoprotein, indicating that this is the mature form of Ebo -GP, Mutational analysis identified a dibasic motif, reminiscent of furin-l ike protease processing sites, as the Ebo-GP cleavage site. However, analys is of Ebo-GP processing in LoVo cells that lack the proprotein convertase f urin demonstrated that furin is not required for processing of Ebo-GP, In s harp contrast to other viral systems, we found that an uncleaved mutant of Ebo-GP was able to mediate infection of various cell lines as efficiently a s the wild-type, proteolytically cleaved glycoprotein, indicating that clea vage is not required for the activation of Ebo-GP despite the conservation of a dibasic cleavage site in all filoviral envelope glycoproteins.