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the generation of multinucleated cells, called syncytia, which are induced by the
fusion of cells that express the envelope glycoprotein and receptors. Abundant
glycoprotein at the surface of the cell could induce cellular death by syncytia
formation, toxicity via receptor interaction, or immune recognition. For these
reasons, the localization and the amount of the oligomerized envelope glycopro-
tein at the host cellular surface are highly modulated by fine trafficking and
sequestration mechanisms. The receptor interference mechanism (either by satu-
ration of binding site on receptor by envelope glycoprotein or by internalization of
receptor by different viral proteins, as it is achieved by some retroviruses; Hunter,
1997) can also limit the amount of receptors available for fusion between infected
cells. The control of the cleavage of the EnvGP to free the fusion peptide is also a
regulation process of the fusion protein fusogenicity (Labonte and Seidah, 2008).
Finally, EnvGP fusion competency may be a late event that occurs during virus
budding, as described for MuLV retroviruses (Rein
,1994).
Proteolytic priming is a common method of controlling the activation
of membrane fusion mediated by viral glycoproteins. The members of the
proprotein convertase (PC) family play a central role in the processing and/or
activation of various protein precursors involved in many physiological processes
and various pathologies such as neurodegenerative pathology, cancer bacterial
toxins activation, and viral infections. The proteolysis of these precursors that
occurs at basic residues within the general motif (K/R)-(X)-(K/R) is mediated by
the proprotein convertases PC1/3, PC2, Furin, PACE4, PC4, PC5 (also called
PC6), and PC7 (also called PC8, LPC, or SPC7), whereas the proteolysis of
precursors within hydrophobic residues performed by the convertase S1P/SKI-1
and the convertase NARC-1/PCSK9 seems to prefer to cleave at a LVFAQSIP
motif (Lahlil
et al.
, 2009). The seven PCs have different, albeit partly, over-
lapping expression patterns and subcellular localization. They have conserved
aminotermini with highest homology in the subtilisin-like catalytic domain.
Data on various infectious viruses revealed that the cleavage of their envelope
glycoprotein precursors by one or more PCs is a required step for the acquisition
of the infectious capacity of viral particles. Indeed, various studies have demon-
strated the capacity of the PCs to correctly cleave a variety of viral surface
glycoproteins. These include the HIV-1 gp160 (Decroly
et al.
, 1996) and surface
glycoproteins of Hong Kong, Ebola virus, the severe acute respiratory syndrome
coronavirus and chikungunya virus (Basak
et al.
et al.
, 2001; Bergeron
et al.
, 2005;
Ozden
, 2008). In parallel, other studies revealed that the inhibition of
processing of these viral surface glycoproteins by the PC inhibitors such as dec-R-
V-K-R-CMK completely abrogated the virus-induced cellular cytopathicity. The
surface glycoproteins of other viruses, particularly the hemorrhagic fever viruses
(Arenaviridae family), such as Lassa (Basak
et al.
et al.
, 2002; Lenz
et al.
, 2001),
Crimean Congo hemorrhagic fever (Vincent
et al.
, 2003), and lymphocytic
choriomeningitis (Beyer
et al.
, 2003), were shown to be cleaved by the
