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expansions throughout millions of years of retrovirus evolution, limited switches
can occur within single infected animals. For example, there is an evolution of
coreceptor usage in HIV-1/AIDS, some
adaptations of ecotropic MuLVs
and formation of polytropic MuLVs, and some evolution of altered receptor
usages in domestic cats infected with FeLV-A (Tailor
in vivo
., 2003).
Several viruses have been reported to use multiple alternative receptors
or even alternative pathways for infection of cells. For example, MV isolates
appear to be capable of using CD46 or SLAM, which both contain single TM
domains (Baranowski
et al
., 2000).
Complex viruses such as herpesviruses that contain several distinct EnvGP are
also typically able to bind to several cell surface components (Baranowski
et al
., 2001; Oldstone
et al
., 1999; Tatsuo
et al
.,
2001; Borza and Hutt-Fletcher, 2002). The foot-and-mouth disease picornavirus
(FMDV) may also use multiple receptors, including heparan sulfates and integrins,
and may, in addition, be able to invade cells via immunoglobulin Fc receptors
when the virus is coated with antibodies (Baranowski
et al
.,
1994). This alternative entry route is also used by the dengue flavivirus, which may
explain the extremely strong pathogenesis that occurs when it reinfects previously
exposed individuals (Baranowski
et al
., 2001; Mason
et al
., 2001). In the case of FMDV, it has not been
established whether heparin sulfate is a true receptor that directly mediates
infection or merely a binding factor that influences infection indirectly by enhanc-
ing virus adsorption. HIV-1 infections are also strongly stimulated by accessory cell
surface binding components including heparan sulfates, glycolipids, and DC-SIGN
(Bounou
et al
., 2001). Similarly, a
paralysis-inducing neurotropic variant of Friend MuLV binds more strongly than
the parental virus to heparan sulfate, and thereby becomes more infectious for
brain capillary endothelial cells while still remaining dependent on the CAT1
receptor (Jinno-Oue
et al
., 2002; Geijtenbeek
et al
., 2000; Pohlmann
et al
., 2001). These examples illustrate how changes in
affinities for accessory binding substances can dramatically alter cellular tropisms
and pathogenesis of viruses, and why it has often been difficult to distinguish such
accessory binding factors from true receptors or coreceptors that are essential for
infections. On the basis of these considerations, we believe that the available
evidence strongly supports our proposal that all virus groups have been severely
constrained in the types of receptors they can employ for infection of cells.
However, some viruses have evolved several pathways for infection, and viruses
such as HIV-1 have evolved distinct sites in a single SU glycoprotein for recogni-
tion of dissimilar receptors and coreceptors.
et al
C. Separation of the binding and fusion functions
The complexity of EnvGP is variable. An example of a very simple fusion protein
is the FAST proteins of Orthoreovirus that do not belong, however, to the family
of the enveloped virus (Barry
et al
., 2010; Shmulevitz and Duncan, 2000). The
