Page 240 - Review of Medical Microbiology and Immunology ( PDFDrive )

mebooksfree.com
mebooksfree.com
mebooksfree.com

mebooksfree.com
mebooksfree.com
mebooksfree.com
mebooksfree.com
mebooksfree.com mebooksfree.com mebooksfree.com acid). They are implicated as the cause of certain “slow” dis- 229 mebooksfree.com
mebooksfree.com
CHAPTER 28 Structure
As described earlier in this chapter, the surface proteins
of the virus, whether they are the capsid proteins or the
eases called transmissible spongiform encephalopathies,
envelope glycoproteins, are the principal antigens against
which include such diseases as Creutzfeldt-Jakob disease in
which the host mounts its immune response to viruses.
humans and scrapie in sheep (see Chapter 44). Because nei-
They are also the determinants of type specificity (often
ther DNA nor RNA has been detected in prions, they are
called the serotype). There is often little cross-protection
between different serotypes. Viruses that have multiple
electron microscopy reveals filaments rather than virus par-
ticles. Prions are much more resistant to inactivation by
serotypes (i.e., have antigenic variants) have an enhanced
ultraviolet light and heat than are viruses. They are remark-
ability to evade our host defenses because antibody against clearly different from viruses (Table 28–1). Furthermore,
mebooksfree.com
mebooksfree.com
one serotype will not protect against another serotype.
mebooksfree.com mebooksfree.com mebooksfree.com and other medical supplies that cannot be autoclaved. mebooksfree.com
ably resistant to formaldehyde and nucleases. However,
they are inactivated by hypochlorite, NaOH, and autoclav-
ing. Hypochlorite is used to sterilize surgical instruments
ATYPICAL VIRUS-LIKE AGENTS
There are four exceptions to the typical virus as described
Prions are composed of a single glycoprotein with a
earlier:
molecular weight of 27,000 to 30,000. With scrapie prions
as the model, it was found that this protein is encoded by a
(1) Defective viruses are composed of viral nucleic acid
and proteins but cannot replicate without a “helper” virus,
single cellular gene. This gene is found in equal numbers in
the cells of both infected and uninfected animals. Further-
which provides the missing function. Defective viruses
usually have a mutation or a deletion of part of their genetic
uninfected as in infected cells. In view of these findings,
material. During the growth of most human viruses, many
posttranslational modifications of the prion protein are
more defective than infectious virus particles are produced.
The ratio of defective to infectious particles can be as high more, the amount of prion protein mRNA is the same in
hypothesized to be the important distinction between the
mebooksfree.com mebooksfree.com mebooksfree.com prion protein cellular) to the abnormal beta-pleated sheet mebooksfree.com
mebooksfree.com
mebooksfree.com
as 100:1. Because these defective particles can interfere
protein found in infected and uninfected cells.
with the growth of the infectious particles, it has been
There is evidence that a change in the conformation
SC
from the normal alpha-helical form (known as PrP , or
hypothesized that the defective viruses may aid in recovery
from an infection by limiting the ability of the infectious
SC
form (known as PrP , or prion protein scrapie) is the
particles to grow.
important modification. The abnormal form then recruits
(2) Pseudovirions contain host cell DNA instead of
viral DNA within the capsid. They are formed during infec-
additional normal forms to change their configuration, and
the number of abnormal pathogenic particles increases.
tion with certain viruses when the host cell DNA is frag-
mented and pieces of it are incorporated within the capsid
Although prions are composed only of proteins, specific
protein. Pseudovirions can infect cells, but they do not
helical form to the pathologic beta-pleated sheet form.
replicate.
(3) Viroids consist solely of a single molecule of circular
Evidence that recruitment is an essential step comes
from “knockout” mice in which the gene for the prion pro-
RNA without a protein coat or envelope. There is extensive cellular RNAs enhance the conversion of the normal alpha-
mebooksfree.com
homology between bases in the viroid RNA, leading to
tein is nonfunctional and no prion protein is made. These
mebooksfree.com mebooksfree.com mebooksfree.com There is some evidence that it is one of the signal transduc- mebooksfree.com
Conventional Viruses mebooksfree.com
large double-stranded regions. The RNA is quite small
mice do not get scrapie despite the injection of the patho-
5
genic scrapie prion protein.
(molecular weight 1 × 10 ) and apparently does not code
for any protein. Nevertheless, viroids replicate, but the
The function of the normal prion protein is unclear.
mechanism is unclear. They cause several plant diseases but
tion proteins in neurons and that it is a copper-binding
are not implicated in any human disease.
protein. Knockout mice in which the gene encoding the
(4) Prions are infectious particles that are composed
prion protein is inactive appear normal. The prion protein
solely of protein (i.e., they contain no detectable nucleic
TABLE 28–1 Comparison of Prions and Conventional Viruses
Feature
Prions
Yes
No
Particle contains nucleic acid
mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com
Yes, encoded by viral genes
Yes, encoded by cellular genes
Particle contains protein
Yes
No
Inactivated rapidly by ultraviolet light or heat
Appearance in electron microscope
Icosahedral or helical symmetry
Filamentous rods (amyloid-like)
No
Yes
Infection induces antibody
No
Yes
Infection induces inflammation
mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com