Biology Reference
In-Depth Information
multinucleated cells called syncytia. In the second case, for pH-dependent
fusion, the interaction between the EnvGP and the receptor leads to the obliga-
tory endocytosis of the virus-receptor complex, and the acidification of endo-
somes triggers conformational changes in the EnvGP. For the pH-dependent
virus, such a fusion can be reproduced in cell culture
or in a liposome-
virus fusion assay in the tube after decreasing the pH, but cannot occur
in vitro
.
Research during the last few years has greatly advanced our understand-
ing of the cell surface receptors for viruses and has provided many surprising
insights. These advances were achieved largely by identification and molecular
cloning of the cell surface or cytoplasmic proteins that have been subverted for
use as viral receptors or cofactor, and by parallel advances in studies of the viral
EnvGP that bind to the receptors.
Another key area of new insights concerns the physical-chemical pro-
cess of viral adsorption and of pulling the virus closely onto the cellular mem-
brane. Indeed, adsorption is a severely limiting step in infections of cultured cells,
and the initial attachment often does not involve the receptors that ultimately
mediate infections (Andreadis
in vivo
et al.
, 2000; Guibinga
et al.
, 2002; Pizzato
et al.
,
1999, 2001; Ugolini
, 1999). Thus, we need to distinguish cell surface
molecules such as heparan sulfate proteoglycans, DC-SIGN, or integrins that
can enhance infections by concentrating retroviruses onto cells (Bounou
et al.
et al.
,
2002; Geijtenbeek
et al.
, 2000; Jinno-Oue
et al.
, 2001; Mondor
et al.
, 1998;
Pohlmann
, 2001) from authentic receptors that induce
conformational changes in EnvGP that are a prerequisite for fusion of the viral
and cellular membranes. In contrast to other cell surface components such as
lectins or proteoglycans that influence infections indirectly by enhancing virus
adsorption onto specific cells, the true receptors induce conformational changes
in the viral EnvGP that are essential for infection. However, it appears that more
and more intracellular proteins have roles in controlling viral host ranges, and the
proteins involved in traffic of intracellular vesicles like endosomes, play a critical
role in entry. Therefore, proteins from pathways specifically characterized might
be considered as a cofactor as their role is not to mediate direct contact with
EnvGP but is crucial for entry. In addition, some viruses are able to use more than
one endocytic pathway and the cellular proteins involved thus direct the virus to
the entry door beneficial for the virus under a particular condition.
Pseudoparticles are retroviridae cores which incorporate heterogeneous
envelope protein from a different virus, possibly of a different family. Their entry
process mimics precisely that of the wild-type viruses from which the envelope
glycoprotein was derived. They represent a useful tool to study molecular pro-
cesses of envelope viruses as they are very flexible, allowing the analysis of
numerous mutants. Moreover, they allow a precise measurement of the infectivity
that depends on the envelope glycoprotein for the entry step and they allow the
establishment of virus-liposome fusion assays.
et al.
, 2001; Saphire
et al.
