Biology Reference
In-Depth Information
number of receptors required. The assembly of a complex containing several
receptors may be a prerequisite for the membrane fusion steps that require
multiple EnvGP molecules to cooperatively participate in this process. For
example, in the case of HIV-1, the presence of more than one CD4 in contact
with the virus enhances the infectivity dramatically and reduces the concentra-
tion of coreceptors needed for infection (Platt
, 1998). Further investigation
of this system has implied that a critical complex containing approximately four
to six coreceptors is a requirement for infection, although it is not known
whether this complex performs a transient role and then disperses or is main-
tained throughout the membrane fusion process (Kuhmann
et al.
, 2000). Despite
some uncertainties, several lines of evidence have suggested that three to six
hemagglutin trimers may cooperatively participate in the influenza A virus-
mediated membrane fusion reaction (Blumenthal
et al.
,
1988) and that multiple envelope glycoprotein trimers are required for rabies
virus-mediated membrane fusion (Roche and Gaudin, 2002). see Table 4.3.
et al.
, 1996; Boulay
et al.
3. The role of cytoplasmic tail in fusion and influence of its length
The cytoplasmic tails of envelope viruses harbor different motifs that are respon-
sible for its trafficking and are variable in length. It is surprising to see that the
cytoplasmic tails of fusion proteins are not exchangeable. For example, when the
HCV E1 and E2 cytoplasmic tails or the F cytoplasmic tails of HRSV (Human
Respiratory Syncytial virus) are substituted for that of VSV-G envelope glyco-
protein (or CD4), the fusogenicity of these envelopes in cell-cell fusion assays
and virus-cell assay (infection) is destroyed (Buonocore
et al.
, 2002; Oomens
et al.
, 2006). Similarly, when the HA glycoprotein is anchored by a GPI, the
entry process is stopped at the hemifusion step (Kemble
et al.
, 1994; Markosyan
et al.
, 2000). The cellular localizations (e.g., cholesterol-rich microdomains) are
sometimes modified, and biochemical modifications (glycosylation, oligomeriza-
tion) can affect the properties of the VSV-G EnvGP (Kemble
., 1994).
Nevertheless, in their initial context, these cytoplasmic tails allow fusion.
For some viruses, regulation of fusion is mediated by the cleavage of the
cytoplasmic tail. For
et al
-retrovirus, in addition to the SU-TM cleavage, a signifi-
cant fraction of virion-associated TM is further processed by the viral protease
removing the C-terminal 16 amino acids of the cytoplasmic domain, the R
peptide.
-Retrovirus virions assemble and bud from infected cells as immature
particles that must undergo an additional proteolytic maturation to become
infectious (Green
., 1994).
This maturation concerns the viral protease-dependent cleavage of the so-called
peptide R at the C-terminus of the cytoplasmic tail. The R peptide inhibits
fusion, and different hypothesis have been proposed. First, the R peptide contains
et al
., 1981; Lavillette
et al
., 1998, 2002; Rein
et al
