Biology Reference
In-Depth Information
D. Screening and development of entry inhibitors using
pseudoparticles
V. Conclusions
Acknowledgments
References
ABSTRACT
Enveloped viruses penetrate their cell targets following the merging of their
membrane with that of the cell. This fusion process is catalyzed by one or several
viral glycoproteins incorporated on the membrane of the virus. These envelope
glycoproteins (EnvGP) evolved in order to combine two features. First, they
acquired a domain to bind to a specific cellular protein, named “receptor.”
Second, they developed, with the help of cellular proteins, a function of finely
controlled fusion to optimize the replication and preserve the integrity of the
cell, specific to the genus of the virus. Following the activation of the EnvGP
either by binding to their receptors and/or sometimes the acid pH of the endo-
somes, many changes of conformation permit ultimately the action of a specific
hydrophobic domain, the fusion peptide, which destabilizes the cell membrane
and leads to the opening of the lipidic membrane. The comprehension of these
mechanisms is essential to develop medicines of the therapeutic class of entry
inhibitor like enfuvirtide (Fuzeon) against human immunodeficiency virus
(HIV). In this chapter, we will summarize the different envelope glycoprotein
structures that viruses develop to achieve membrane fusion and the entry of the
virus. We will describe the different entry pathways and cellular proteins that
viruses have subverted to allow infection of the cell and the receptors that are
used. Finally, we will illustrate more precisely the recent discoveries that have
been made within the field of the entry process, with a focus on the use of
pseudoparticles. These pseudoparticles are suitable for high-throughput screen-
ings that help in the development of natural or artificial inhibitors as new
therapeutics of the class of entry inhibitors.
2011, Elsevier Inc.
I. INTRODUCTION
Enveloped viruses have a core incorporating the genetic material of the virus
surrounded by a lipidic membrane acquired from the cells they bud from. Their
genetic material enters target cells following the merging of their membrane with
the membrane of the cells at either the plasma membrane or the membrane of
another internal compartment. The process of membrane merging is called
