C h a p t e r 1 4
Mechanisms of Infectious Disease
299
The prion protein (PrP) is a human protein expressed on
the cell surface. Its normal role is not well understood,
but it is hypothesized to be involved in cell adhesion, cell
binding, copper metabolism, or in synaptic function.
Recent studies have shown that the prion proteins
in disease (called PrP
SC
) are actually altered or mutated
forms of a normal host protein called PrP
C
. Differences
in the posttranslational structure cause the two proteins
to behave differently. The PrP
SC
is resistant to the action
of proteases (enzymes that degrade excess or deformed
proteins) and aggregates in the cytoplasm of affected
neurons as amyloid fibrils. The normal PrP
C
is protease
sensitive and appears on the cell surface.
Prion diseases present significant problems to the
medical community because their method of replica-
tion is not clearly understood. Based on current mod-
els, it is believed that PrP
SC
binds to the normal PrP
C
on
the cell surface, causing it to be processed into PrP
SC
,
which is released from the cell and then aggregates into
amyloid-like plaques in the brain. The cell then replen-
ishes the PrP
C
and the cycle continues. As PrP
SC
accu-
mulates, it spreads within the axons of the nerve cells,
causing progressively greater damage to host neurons
and the eventual incapacitation of the host. In addition,
because prions lack reproductive and metabolic func-
tions, the currently available antimicrobial agents are
useless against them.
Viruses
Viruses are the smallest obligate intracellular patho-
gens. They have no organized cellular structures but
instead consist of a protein coat, or capsid, surround-
ing a nucleic acid core, or genome, of RNA or DNA—
never both (Fig.
14-1
). Some viruses are enclosed within
a lipoprotein envelope derived from the cell membrane
of the parasitized host cell. Enveloped viruses include
members of the herpesvirus group and paramyxovi-
ruses, such as influenza and poxviruses. Certain viruses,
enveloped in buds pinched from the cell membrane, are
continuously shed from the infected cell surface.
The viruses of humans and animals have been cat-
egorized somewhat arbitrarily according to various
characteristics. These include the type of viral genome
(single-stranded or double-stranded DNA or RNA),
physical characteristics (e.g., size, presence or absence
of a membrane envelope), the mechanism of replica-
tion (e.g., retroviruses), the mode of transmission (e.g.,
arthropod-borne viruses, enteroviruses), target tissue,
and the type of disease produced (e.g., hepatitis A, B, C,
D, and E viruses), to name just a few.
Viruses are incapable of replication outside of a living
cell. They must penetrate a susceptible living cell and
use the biosynthetic machinery of the cell to produce
viral progeny. The process of viral replication is shown
in Figure 14-2. Not every viral agent causes lysis and
death of the host cell during the course of replication.
Some viruses enter the host cell and insert their genome
into the host cell chromosome, where it remains in a
latent state for long periods without causing disease.
Under the appropriate stimulation, the virus undergoes
active replication and produces symptoms of disease
months to years later. Members of the herpesvirus group
and adenovirus are the best examples of latent viruses.
Herpesviruses include the viral agents of chickenpox
and zoster (varicella-zoster), cold sores (herpes simplex
virus [HSV], usually type 1), genital herpes (HSV, usu-
ally type 2), infectious mononucleosis (cytomegalovirus
or Epstein-Barr virus), and Kaposi sarcoma (human her-
pesvirus 8). The resumption of the latent viral replica-
tion may produce symptoms of primary disease (e.g.,
genital herpes) or cause an entirely different symptom-
atology (e.g., shingles instead of chickenpox).
Since the early 1980s, members of the retrovirus
group have received considerable attention after iden-
tification of the human immunodeficiency viruses (HIV)
as the causative agent of acquired immunodeficiency
syndrome (AIDS). The retroviruses have a unique mech-
anism of replication. After entry into the host cell, the
viral RNA genome is first translated into DNA by a
viral enzyme called
reverse transcriptase
(see Chapter
16). The viral DNA copy is then integrated into the host
chromosome where it exists in a latent state, similar to
the herpesviruses. Reactivation and replication require a
reversal of the entire process. Some retroviruses lyse the
host cell during the process of replication. In the case of
HIV, the infected cells regulate the immunologic defense
system of the host and their lysis leads to a permanent
suppression of the immune response.
In addition to causing infectious diseases, certain
viruses also have the ability to transform normal host
cells into malignant cells during the replication cycle.
This group of viruses is referred to as
oncogenic
and
includes certain retroviruses and DNA viruses, such as
Virion
Capsid
Nucleic acid genome
(DNA or RNA)
Envelope
A
B
FIGURE 14-1.
(A)
The basic structure of a virus includes a
protein coat surrounding an inner core of nucleic acid (DNA or
RNA).
(B)
Some viruses may also be enclosed in a lipoprotein
outer envelope.
