Biology Reference
In-Depth Information
and acquired antiviral immune responses are effective in clearing the
virus (Mattioli 2004).
4
On the other hand, HBV and HCV can per-
sist in the host for a long time, often the entire life of the host.
5
In
such cases, there is an initial acute phase of infection when the virus
employs strategies to avoid host innate defenses, escapes the acquired
immunity and blocks the apoptotic clearance of infected cells to finally
establish chronic infection in the host.
In this chapter we will discuss the innate defense, apoptosis and
cell survival pathways and the mechanisms through which hepatitis
viruses modulate these pathways to establish a successful infection in
the host. An introduction to the genomic organization of these
viruses and the different proteins they encode is also provided to aid
and orient the reader for a better understanding of how these differ-
ent proteins manipulate the host defense.
Genome Structure and Organization
of Hepatitis Viruses
Hepatitis A Virus
HAV belongs to the family
Picornaviridae
and the genus Hepatovirus.
6-8
It has a 7.5 kb positive sense polyadenylated RNA genome with
untranslated regions (UTRs) at either termini.
9
The 5
-UTR contains
an internal ribosome entry site (IRES) for cap independent transla-
tion and is covalently attached to the viral protein 'g' (VPg) (Fig. 1A).
A single open reading frame encodes a polyprotein of 252 kDa that is
processed to yield structural and nonstructural proteins. The P1
region located at the amino-terminal end encodes the structural pro-
teins VP1, VP2, VP3 and VP4, while the P2 and P3 regions encode
the nonstructural proteins associated with viral genome replication
and modulation of the host cell.
′
Hepatitis B Virus
HBV is a double-stranded DNA virus and a member of the family
Hepadnaviridae
. The viral genome is approximately 3.2 kb in size
and has an unusual structure comprising two linear strands of DNA
