Biology Reference
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an Y-X-X-internalization motif, and the removal of this motif following the
cleavage of the R peptide might result in a higher amount of envelope at the
surface membrane and thus more fusion (Song
, 2003). Second, following
the R peptide cleavage, the remaining cyt tail forms a membrane-embedded
amphiphilic alpha-helix domain that destabilizes the membrane (Rozenberg-
Adler
et al.
, 1998). Third, it has been proposed that as the R
peptide contains a palmitoylation, its removal induces the close trimerization of
the cyt tail and drastic conformational changes in the ectodomain of Env
(Aguilar
et al.
, 2008; Zhao
et al.
, 2003) which might influence Env fusogeneity by destabilizing
SU-TM complexes. These conformational changes are necessary for the isomer-
ization of the SU-TM disulfide MLV Env (Loving
et al.
, 2008). This R peptide
cleavage is the last step leading to a fusion competent infectious MLV retrovirus,
but this final modification does not exist in lentiviruses which harbor a long
cytoplasmic tail. However, truncations of the long cytoplasmic domains of
lentiviral Env proteins occur under certain culture conditions (Chakrabarti
et al.
et al.
, 1989) and increase Env fusogenicity in a similar way to mutated truncated
versions of SIV, HIV-1, and HIV-2 Envs (Mulligan
et al.
, 1992; Spies
et al.
, 1994;
Wilk
, 1992). This regulation is a hallmark of adaptation of endogenous
retroviruses, as this cleavage is fulfilled by a cellular protease that activates the
endogenous EnvGP HERV-W in relevant tissues involved in placenta develop-
ment. It is interesting to note that for most viruses (and not only the
et al.
-retrovirus),
the truncation of the cytoplasmic tail increases the fusogenicity of the EnvGP, as
is seen in paramyxoviruses (Moll
, 2002). In many cases, this truncation
seems to increase the cell surface expression (since cellular trafficking signals in
the cytoplasmic tails are modified), which may explain the increase of fusogeni-
city. For certain other Env, the truncation leads to conformational changes in the
ectodomain which lowers the activation threshold for fusion, resulting in en-
hanced Env fusion activity and kinetics (Aguilar
et al.
et al
., 2003; Cote
et al
., 2008;
Spies
., 1998). Finally, the cleavage of the cytoplasmic tail
sometimes allows, at least partially, a cell-cell fusion at neutral pH (pH-indepen-
dent), although the entry of the virus remains pH-dependent. The notion of pH-
dependence, seems in this case, to be due to a specific conformation or a particular
density of envelope glycoprotein (Cote
et al
., 1994; Zhao
et al
et al
., 2008).
4. The transmembrane proximal region
Numerous studies on several viruses have highlighted the critical role of the
pretransmembrane sequence (PTM), also called the membrane proximale region
or the juxtamembrane domain (JMD), which is rich in aromatic amino acids.
The class I fusion glycoproteins of coronavirus, lentivirus (HIV, SIV, FIV), ebola
virus (Munoz-Barroso
et al.
, 1999; Saez-Cirion
et al.
, 2003), and many other
