Biology Reference
In-Depth Information
entry through acid compartments which modify protein structures, the entry by
different pathways of endocytose, and the rapidity of the conformation changes
of HA. Some modifications can be made to these peptides to increase their
efficiency for viruses that fuse at the plasma membrane. For three paramyxo-
viruses, HPIV-3, a major cause of lower respiratory tract diseases in infants, and
the emerging zoonotic viruses Hendra virus (HeV) and NiV, which cause lethal
central nervous system (CNS) diseases, the addition of cholesterol to a para-
myxovirus HRC-derived peptide (derived from the heptad repeat immediately
preceding the transmembrane domain) increased antiviral potency by 2 log units
(Porotto
, 2010). This enhanced activity is the result of the targeting of the
peptide to the plasma membrane. The cholesterol-tagged peptides on the cell
surface create a protective antiviral shield, target the F protein directly at its site
of action, and expand the potential utility of
et al.
inhibitory peptides
for
paramyxoviruses.
III. HOW VIRUSES SUBVERT DIFFERENT CELL PROTEINS
FOR ENTRY?
A. Definition of receptors, adsorption molecules, and cofactors
The definition of a receptor is very complicated and has limitations. It is
sometimes difficult to distinguish between “simple” receptors that mediate ad-
sorption or binding and that may not even initiate conformational changes, and
“critical” receptors for fusion which, upon binding, will generate the conforma-
tional changes that will allow the exposure of the fusion peptide and lead to
membrane fusion. Some cellular molecules are also involved in the localization
or trafficking of viral receptors and these are important cofactors of entry.
Another ambiguity is the role of enzymatic activities. Some are necessary to
process the fusion protein inside producer cells, or inside the endosomes of target
cells, and they are necessary to activate the potential of the EnvGP for mem-
brane fusion. While it is inaccurate to consider them as “receptors”, they are
certainly critical cofactors.
1. Virus adsorption
All viruses likely bind at least weakly to multiple cell surface components such as
heparan sulfate proteoglycans, DC-SIGN, integrins, or glycolipids (Bounou
et al
.,
2002; Cantin
et al
., 1997; Fortin
et al
., 1997; Jinno-Oue
et al
., 2001; Mondor
et al
.,
1998; Saphire
., 1999, 2001). Although such binding substances probably do
not induce conformational changes in EnvGP that are necessary for membrane
fusion, they can enhance viral adsorption and substantially increase efficiencies
et al
