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The genome of retroviruses contains three major coding regions for
virion proteins, gag, pol and env. Gag encompasses information for
nonglycosylated viral proteins that form the matrix, the capsid and
the nucleoprotein structures. From pol derive reverse transcriptase
and integrase, and env codes for the surface glycoproteins of the
virion which consist of a transmembrane and a surface domain,
linked by disulfide bonds. A viral protease is derived eitherfrom
the gagorfrom the pol coding region, depending on the virus. Simple
retroviruses contain only this elementary gag, pol, and env coding
information. Once integrated, they are able to multiply
efficiently, using the cellular transcriptional and replication
machineries without intervention of viral transacting factors. Most
oncogenic retroviruses belong in this category. Complex
retroviruses, on the other hand, encode additional nonstructural
proteins from multiply spliced messages. These proteins play
important regulatory roles in the life cycle of the virus. They
function as transacting factors that, in concert with cellular
regulatory proteins, control viral gene expression and function and
are essential components in the replication of complex
retroviruses. To this category belong the lentiviruses, the
spumaviruses and a group of oncogenic retroviruses that includes
human T cell leukemia virus (HTLV) and bovine leukosis virus(BLV).
Borna disease was first described over 200 years ago, in what is
now Southeastern Germany, as a fatal neurologic affliction of
horses and was considered a curiosity for many decades. The
causative agent was unknown, and the animal species infected in
nature were limited to horses and sheep. Today, as described in
this volume, the host range has extended to all warm-blooded
animals, the genes and proteins of the virus have been identified,
and many of the mechanisms responsible for behavioral disturbances
are understood. Serologic studies suggest that BDV or related
agents are likely to play a role in human neuropsychiatric
diseases.
Genetic / DNA immunization represents a novel approach to vaccine
and immune therapeutic development. The direct injec tion of
nucleic acid expression cassettes into a living host results in a
limited number of its cells becoming factories for production of
the introduced gene products. This host-inappropriate gene
expression has important immunological consequences, resulting in
the specific immune activation of the host against the gene
delivered antigen. The recent demonstration by a number of
laboratories that the induced immune responses are functional in
experimental models against both specific infectious diseases and
cancers is likely to have dramatic consequences for the develop
ment of a new generation of experimental vaccines and immune
therapies. This technology has the potential to enable the pro
duction of vaccines and immune-based therapies that are not only
effective immunologically but are accessible to the entire world
(rather than just to the most developed nations). Vaccine
Development Vaccination against pathogenic microorganisms
represents one of the most important advances in the history of
medicine. Vaccines, including those against polio, measles, mumps,
rubella, hepatitis A, hepatitis B, pertussis and other diseases,
have dramatically improved and protected more human lives than any
other avenue of modern medicine. The vaccine against smallpox, for
example, has been so successful that it is now widely believed that
this malicious killer, responsible for more deaths in the twentieth
century than World Wars I and II combined, has been removed from
the face of the earth.
The humoral response of the immune system to a foreign antigen
usually requires the recognition of two antigenic determinants. The
one, called the carrier, is recognized by T-Iymphocytes, the other,
called the hapten, by B-Iympho cytes. As a consequence, T - and
B-Iymphocytes proliferate, B-Iymphocytes produce hapten-specific
antibodies, and the system develops memory to the antigens. It was
long thought that antigens would form a bridge to mediate the
cooperation of T - and B-Iymphocytes. However, it now appears that
antigens are broken down to fragments which then act as carrier
determinants for T -lymphocytes. The cells which originally process
antigen are called an tigen-presenting cells. They have phagocytic
properties. They can take up and degrade antigens, in the case of
pro teins to peptides. The peptides of protein antigens reappear on
the surface of the antigen-presenting cells, where they must become
associated with membrane proteins encoded by genes of the major
histocompatibility complex (MHC) in order to be recognized by
T-Iymphocytes. To activate helper T-Iym phocytes which cooperate in
antibody responses, MHC class II molecules have to be expressed on
the surface of the antigen-presenting cells. Once T -lymphocytes
have be come activated, they are ready to cooperate with B cells."
Lyssaviruses are the etiological agents of rabies, one of the
oldest documented and feared maladies in medical history. The last
century has been particularly fruitful in regard to progress in
Iyssavirus phylogenetic affinities, diagnostics, pathogenesis,
molecular virology and epidemiology, pro phylaxis and control. Yet,
despite these academic and practical advances in research, the
age-old horror evoked by rabies is still very real, with only four
documented human recoveries once symptoms are realized. After
decades of intense scrutiny and four recent books describing rabies
and its viral relatives, there is still much to be learned. The
great authority on rabies, Karl Habel, once related an incident of
a very distraught elderly woman, who showed symptoms of
neurological disease. She told Habel, "I don't need a physician. I
know I have rabies. My beloved dog had rabies and died. Look", she
exclaimed, while flinging down a goblet of water, "I have
hydrophobia". Habel asked for her confinement for psychiatric
examination.
Nitric Oxide (NO) an endogenous free radical, has been shown
recently to mediate several important biological effects. It plays
a neuro-transmitter like role in vascular endothelium, a
scond-messenger role in N-methyl-D-aspartate (NMDA) responsive
neurons in the central nervous system (CNS), a neurotoxic role
after its release from these neurons, and a cytotoxic role after
its release by macrophages.
This volume reviews among other topics the basic chemistry and
physical properties of S-nitrosothiols (RS-NO) and their
biochemical mechanisms of action, NO synthase isozymes, NO synthase
structure, mechanisms of NO synthesis, regulation of NOS expression
and posttranslational modification, and mechanisms involving NO of
CNS's damage in virus infections.
The diversity of antigen-binding structures of antibody molecules
is so vast that every conceivable antigen can be bound by an
antibody molecule within the immune system. This is true even for
the antigen binding sites of antibodies called idiotypes, which are
bound by complementary bind ing sites of other antibodies called
anti-idiotypes. Thus, anti-idiotypes are structural homologues of
antigens. These idiotypic-anti-idiotypic interactions constitute a
network within the immune system. Since one lymphocyte produces
only one type of antibody molecule, this network is in fact a
network of cells. We expect that the network is functional: the
appearance of antigen will disturb the equilibrium of the network
at the point where it competes with the anti idiotypic lymphocyte
for binding to the idiotypic lympho cyte. It has been known for
quite some time that anti idiotypic antibody can be used to prime
the immune system for memory to an antigen that it has never seen.
This phe nomenon is now being explored for possible use in immuni
zation against viruses, bacteria, parasites and tumors as well as
for the modulation of autoimmunity. The ability of anti-idiotypes
to mimic, both antigenically and function ally, the corresponding
biologically active molecules seen by an idiotypic antibody was
first demonstrated for the hormone insulin and is now being
observed in many other systems. The papers assembled in this
volume. bring the reader to the cutting edge of the potential
practical applica tions of the network theory of the immune
system."
Additional Contributors Include E. J. Eichwald, H. S. Lawrence, S.
V. Boyden And Many Others.
Additional Contributors Include E. J. Eichwald, H. S. Lawrence, S.
V. Boyden And Many Others.
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