Biology Reference
In-Depth Information
Fig. 5.
Receptor and co-receptor mediated entry of virus into CD4
+
T-
cell. The figure is adapted from Moore and Doms.
34
After CD4 binding,
gp120 undergoes a conformational change and exposes the co-receptor
binding site on Env (Panel B). The triggered Env binds to a seven-trans-
membrane domain co-receptor (third section, CoR). The hydrophobic
fusion peptide at the N terminus of gp41 becomes exposed and inserts into
the membrane of the cell (Panel C). Whether this results from CD4 binding
or co-receptor binding is not known. Co-receptor binding ultimately results
in formation of a six-helix bundle in which the helical HR2 domains in each
gp41 subunit fold back and pack into grooves on the outside of the triple-
stranded HR1 domains (Panel D), bringing the fusion peptide and trans-
membrane domain of gp41 (and their associated membranes) into close
proximity. It is likely that several Env trimers need to undergo this confor-
mational change in order to form a fusion pore, although here only two
trimers are depicted. It is not known whether gp120 remains associated dur-
ing the fusion process or dissociates from gp41. Although only a single CD4-
binding event is shown, multiple CD4-binding events may be needed to
activate a single Env trimer.
immune responses of the host and provide a means of immune escape.
The receptor and co-receptor dependent entry process of HIV into
target cells is depicted in Fig. 5.
34
Interaction of HIV Env with the
CD4 is an obligatory step for virus entry into the cell; therefore, as
expected, the CD4 binding domain of gp120 is a highly conserved,
complex, and conformational dependent region. Hence, the
CD4
binding site of Env (CD4BS)
may be an excellent target for
immune intervention. Consistent with this hypothesis, many mAbs
