Biology Reference
In-Depth Information
In terms of the activation process of the membrane fusion and the need
for particular microdomains, it is not always clear why the viruses are using so
many different pathways. It is possible that the viruses that evolved to fuse
intracellularly have a selective advantage to release their genome to specific
intracellular sites that will allow the rapid and efficient establishment of the
infectious cycle. One selective advantage could also be the requirement for
particular lipid microdomains, like those enriched in cholesterol. Indeed, it
was shown that contrary to the class II flavivirus dengue virus and the yellow
fever virus, the E1 fusion protein from Semliki forest virus (SFV) binds choles-
terol which explains its dependence for cholesterol and compartment containing
cholesterol (Umashankar
, 2008). For other viruses, the dependence on
cholesterol is linked to bulk effects on membrane fluidity and the maintenance of
particular microdomains where receptors are located and where they have some
particular diffusion.
et al.
C. The entry process can be achieved by different number of EnvGP
In addition to these dichotomies of pH-independent or pH-dependent fusion
process, of plasma or endosomes membrane fusion, the mechanisms of activation
of the fusion proteins of the different enveloped viruses are very diverse. Some
reactions of fusion are triggered by the interaction of one envelope glycoprotein
with a unique receptor. One example is the interaction of the envelope glyco-
protein SU-TM of the
-retrovirus with the multitransmembrane receptor
(Table 4.1). In another case, one unique envelope glycoprotein can interact
with several receptors. For example, the fusion of HIV-1 is triggered by the
sequential interaction of the SU gp120 with the CD4 receptor, followed by
interaction with a coreceptor such as CCR5 or CXCR4, chimiokine receptors
of seven transmembrane domains (Hunter, 1997). Previously, it was believed
that binding to receptors directly triggered a series of conformational changes in
the viral EnvGP culminating in fusion of the viral and cellular membranes.
However, new evidence suggests that
-retroviral association with receptors
triggers an obligatory cooperative interaction or cross-talk between EnvGP on
the viral surface for HIV and MLV (Tailor
, 2003). If this intermediate step
is prevented, infection fails. Conversely, in several circumstances, this cross-talk
can be induced in the absence of a cell surface receptor for the virus, in which
case, infection can proceed efficiently. This new evidence strongly implies that
the role of cell surface receptors in infections of
et al.
-retroviruses (and perhaps of
other enveloped animal viruses) is more complex and interesting than was
previously imagined.
In all these cases, the EnvGP have a double function attachment to the
receptor and an exclusive role in fusion in the same protein. However, for other
viruses, these two functions are filled by different proteins. The E2 protein of the
