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Orthoreovirus genus includes some no-enveloped viruses that cause the cell-cell
fusion of infected cells. This fusion activity is due to the small no-structural
membrane viral proteins named FAST proteins (fusion-associated small trans-
membrane protein), in size ranging between
10 and 15 kDa. The FAST
protein ectodomains are very small, with extreme cases of only 20 residues, and
contain hydrophobic short regions with/without acid properties, and a myristoy-
lation site. Though their small size challenges their ability to form a hairpin
structure, these FAST proteins expressed alone are sufficient to induce the
membrane fusion (Barry
., 2010; Shmulevitz and Duncan, 2000). Surprisingly,
they are able to traffic as far as the plasma membrane without inducing intracel-
lular disorder. Indeed, by opposition, the expression of retroviral TM or ortho-
myxovirus HA2 alone does not lead to cell surface membrane expression, and
these subunits are blocked intracellularly. The fusion induced by the FAST
protein is very broad, which questions their use of a particular protein receptor.
Thus, some fusion proteins are simple and possess solely the fusion function, and
others comprise several domains in addition to the domain involved in fusion.
The function of some of these domains has remained more or less independent
from the fusion domain, and sometimes, they can be naturally separated in
different proteins (i.e., H and F from paramyxoviruses) or experimentally on
different fragments, as explain below. Such is the case of the
et al
-retroviruses for
which the function of binding to the receptor can be separated from the function
of fusion. This line of inquiry was initiated by the studies of Bae
. (1997)
relating to a conserved PHQ motif that occurs near the amino-terminal ends of
SU glycoproteins in all
et al
-retroviruses. Mutation of this PHQ motif blocked
membrane fusion but had no effect on receptor attachment. Subsequently, we
discovered that noninfectious
-retrovirions lacking this histidine could be
transactivated by addition of a soluble SU or an amino-terminal fragment of
SU, called the receptor-binding domain (RBD), to the cultured cells (Lavillette
et al
., 2000). Interestingly, studies by Overbaugh and coworkers have demon-
strated that similar transactivation processes can occur in natural infections by
-retroviruses. Specifically, they found that infections by the immunosuppressive
FeLV-T virus, which has a Pro in place of His in its PHQ motif, require transacti-
vation either by a soluble FeLV-B-related SU glycoprotein termed FELIX that is
endogenously expressed in cat T cells or by an FeLV-B SU glycoprotein
(Anderson
., 2000). This activating process parallels that of herpes simplex
virus for the transmission of a fusogenic signal among the EnvGP of the herpes
simplex virus on receptor binding by glycoprotein gD. The soluble gD ectodomain
has been shown to allow entry of engineered HSV-1 virus particles that lack gD
(i.e., gD-null mutants; Cocchi
et al
., 2004). The evidence reviewed provides very
strong support for the hypothesis that attachment of viruses to their receptors
initiates a pathway that obligatorily contains intermediate steps. These interme-
diate steps very likely include viral association with multiple receptors,
et al
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