Biology Reference
In-Depth Information
glands, lymphocytes and other tissues. Human cytomegalovirus
(HCMV or HHV-5), a leading cause of birth defects, and the human
herpesvirus types 6 and 7 (HHV-6, HHV-7), are members of this
subfamily. The two known human pathogens of the gammaher-
pesvirus subfamily, Epstein-Barr virus (EBV or HHV-4) and Kaposi's
sarcoma-associated herpesvirus (KSHV or HHV-8), are both associ-
ated with lymphomas and other cancers. They have a more restricted
host range than viruses of the other two subfamilies. Table 2 lists the
major virion-associated proteins of representative human her-
pesviruses from the three subfamilies.
In this chapter, we will first provide a general account of the cur-
rent understanding of herpesvirus lytic replication and capsid assem-
bly pathway. We will then review recent structural studies by focusing
on three human herpesviruses representative of the three subfamilies:
the alphaherpesvirus HSV-1, the betaherpesvirus HCMV, and the
gammaherpesvirus KSHV.
Lytic Herpesvirus Infection and Viral Assembly
Our current understanding of the general aspects of the herpesvirus
lifecycle can be traced back to earlier studies of the prototypical her-
pesvirus, HSV-1, as well as similar ultrastructural investigations of
other herpesviruses.
4-7
Many of these studies were derived from elec-
tron microscope observations of the morphology of viral particles in
thin-sectioned, virus-infected cells.
Herpesvirus infection begins with the attachment of virus particles
to glycoprotein receptors on the surface of the host cell (Fig. 1).
Several cellular receptors for herpesvirus attachment have been identi-
fied, including CD21 for EBV, CD46 for HHV-6, and CD4 as a com-
ponent of HHV-7 binding.
8-11
HCMV binds to a 30 kDa glycoprotein
cell membrane receptor, and subsequent virus entry is mediated by
HCMV glycoprotein B (gpUL55).
12,13
VZV endocytosis is facilitated
by a specific gE:gI Fc receptor that resembles the cellular Fc-
γ
RII.
14
The integrin
α
3
β
1
appears to have a role in KSHV endocytosis.
15
Upon binding to the receptor, the viral envelope fuses with either the
host membrane or the membrane of an endocytic vesicle, leading to
