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gives rise to the fusion pore (Chernomordik and Kozlov, 2008). Interestingly, the
helix breaker residues within the tm domain are critical for the fusogenicity of
different retroviral Env, such as HIV (Owens
, 1994) and Mo-MLV (Taylor
and Sanders, 1999), being important for both the hemifusion and pore opening
step of the fusion process. In addition, hemifusion intermediate has been
detected in the case of HIV Env-mediated fusion (Munoz-Barroso
et al.
, 1998)
by using peptide inhibitors that target a prefusion or prehairpin structure such as
HIV-1 gp41 T-20. Once the pore is formed, it allows a connection between two
compartments initially separated by the apposed membranes.
The ability of the membrane to hemifuse and develop a fusion pore has
been found to depend on the lipid microdomain composition, for example,
cholesterol (Chernomordik and Kozlov, 2003). Indeed, a potential lipid depen-
dence of virus entry processes was first deduced from experiments on influenza
virus, implying a role for detergent-resistant lipidic microdomain (Takeda
et al.
,
2003). For retroviruses, the tm palmitoylations which contribute to the Env
localization in detergent-resistant lipidic microdomain domains (Li
et al.
et al.
, 2002)
indirectly influence the fusion process (Ochsenbauer-Jambor
, 2001). As an
alternative to the lipidic pore hypothesis, a direct fusion mechanism has also
been proposed. The fusion pore is a full proteic channel-like structure dependent
only on the transmembrane domains of the glycoproteins. In this model, the pore
is opened by the joining of
et al.
two hemipores
located on each membrane
(Chernomordik and Kozlov, 2005, 2008).
After fusion pore opening and enlargement (Melikyan
, 2005), the
genetic material enters the cytoplasm of the cell, instigating the virus cell cycle.
et al.
B. pH-dependent and -independent molecular switches
The fusion of the viruses that enter directly at membrane plasmic level (as with
the paramyxoviruses and most retroviruses) is triggered by the activation of the
viral envelope protein at neutral pH. In this case, only the binding of the virus to
its receptor activates the fusogenic potential of the complexes of EnvGP. This
mechanism is pH-independent. In the case of retroviruses, the binding of the
surface subunit (SU) to its receptor induces conformational changes not only in
itself but also in the TM with which it interacts, thus inducing fusion. This
activation at neutral pH permits the envelope glycoprotein of pH-independent
viruses, in certain experimental conditions or
, to induce the fusion
between the cells expressing the envelope glycoprotein and the cells expressing
the receptor (Harrison, 2008; Kielian and Rey, 2006; Weissenhorn
in vivo
., 2007).
This intercellular fusion, by merging their plasma membranes, places the cell
cytoplasms in continuity, and one or more cells become giant multinucleated
cells named syncytia.
et al
