Biology Reference
In-Depth Information
In general, the cleavage of the fusion proteins is mandatory for most class I
proteins to render them competent for fusion (Earp
, 2005; Harrison, 2005).
Exceptions are the envelope glycoprotein from Ebola or SARS-CoV viruses,
classified as class I on the grounds of the three-dimensional structure of one of
their fragments, which are not cleaved but yet are functional. Though an N-
terminal fusion peptide is predicted in the potential transmembrane subunit
(localized by analogy to homologous viruses), their functionality can be
explained also by the presence of an internal fusion peptide (Ebola). Another
explanation of their functionality is their requirement for the L or B cathepsins
that cleave the EnvGP during endocytosis (see below). The number of com-
plexes on the surface of viruses harboring class I fusion proteins is very variable. It
seems that lentiviruses have only 10-20 SU-TM trimers, whereas the corona-
viruses have hundreds of trimers coating the surface, giving them their charac-
teristic morphology of “crown” which is the origin of the name of this family
(Tables 4.1 and 4.2).
The process of assemblage and biosynthesis of class virus II is very different
totheclassIproteins(Kielian and Rey, 2006)(Fig. 4.2B). During biosynthesis, the
alphavirus (E1) and flavivirus (E) fusion proteins fold cotranslationally with a
companion or regulatory protein, termed p62 (or PE2) for alphaviruses and prM
for flaviviruses (Garoff
et al.
,2004). This heterodimeric interaction is important for
the correct folding and transport of the fusion protein. Both p62 and prM are
cleaved by the cellular protease furin late in the secretory pathway, in a maturation
reaction that is a crucial regulatory step for subsequent virus fusion (Salminen
et al.
et al.
,
1992; Stadler
,2003a). Though this
cleavage in the envelope glycoprotein complex is important, contrary to class I
fusion protein, it is not crucial, since mutated alphavirus and flavivirus for which
the regulating proteins are not cleaved have only a decreased infectivity (Salminen
et al
et al.
, 1997; Wengler, 1989; Zhang
et al.
., 2003b). In the case of the SFV alphavirus, the fusion
process induced by the uncleaved fusion proteins can be a trigger after treatment of
the virus at pH5 or less, rather than the normal fusion threshold pH 6 of the wild-
type virus (Salminen
., 1992; Zhang
et al
., 2003a). This variation in the
threshold of pH of the fusion is necessary for the dissociation of the heterodimer.
The class II fusion proteins are either homodimers or heterodimers (E homodimer
for the flaviviruses or E2-E1 heterodimer for alphaviruses) that form an envelope
netting the viral membrane (Lescar
et al
., 1992; Zhang
et al
,1995). The internal
fusion peptide is masked at the interface of the dimers at the extremity of a long beta
sheet. One important difference between these two groups of viruses is the budding
site (Garoff
et al.
, 2001; Rey
et al.
., 2004). In alphaviruses, the p62-E1 complex is transported to the
plasma membrane, and the heterodimer interaction is maintained after p62 proces-
sing. New virions bud at the plasma membrane, in a process that is driven by lateral
contacts between E2 and E1 heterodimers (E2 being the mature companion
protein) to induce the required curvature of the lipid bilayer, in combination
et al
