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Immune Disease H-L
Hepatitis Herpes simplex
virus Herpes simplex
virus 1 and 2 (HSV-1 and HSV-2) are two
strains of the herpes virus family, Herpesviridae, which cause
extremely
painful infections in humans. They are also called Human Herpes Virus 1
and 2
(HHV-1 and HHV-2). An infection is
marked by watery blisters in the skin
or mucous membranes (such as the mouth or lips) or on the genitals.
Lesions heal with a scab characteristic of herpetic disease. However,
the
infection is persistent and symptoms may recur periodically as
outbreaks of
sores near the site of original infection. After the initial, or
primary,
infection, HSV becomes latent present in the cell bodies of nerves in
the area.
When it becomes reactivated, it is produced in the nerve cell and
transported
to the skin via the nerve's axon. Herpes is
contagious if the carrier is producing and shedding
virus. This is especially likely during an outbreak but possible at
other
times. There is no cure yet, but there are treatments which reduce the
likelihood of viral shedding. An HSV infection on the lips is commonly
known as
a "cold sore" or "fever blister". The blisters resemble
those of chickenpox, an infection caused by another member of the
alpha-Herpesviridae subfamily, Varicella Zoster Virus (VZV), also known
as
Human Herpes Virus 3 (HHV-3). Viral structure The human
herpesviruses all share some common
properties. One shared property is virus structure and herpesviruses
are
composed of relatively large double-stranded, linear DNA genomes
encoding
100-200 genes encased within an icosahedral protein cage called the
capsid
which is itself wrapped in a lipid bilayer membrane called the
envelope. This
particle is known as the virion. Entry of HSV
into the host cell involves interactions
of several viral glycoproteins with cell surface receptors. The virus
particle
is covered by an envelope which, when bound to specific receptors on
the cell
surface, will fuse with the cell membrane and create an opening, or
pore,
through which the virus enters the host cell. The sequential
stages of HSV entry are analogous to
those of other viruses. At first, complementary receptors on the virus
and cell
surface bring the two membranes into proximity. In an intermediate
state, the
two membranes begin to merge, forming a hemifusion state. Finally, a
stable
entry pore is formed through which the viral envelope contents are
introduced
to the host cell. In the case of Herpes virus, initial interactions
occur when
glycoprotein C, on the surface of the viral envelope, binds to a cell
surface
particle, heparan sulfate. Glycoprotein D binds specifically to the
herpesvirus
entry mediator receptor (HVEM), thus providing a strong, fixed
attachment to
the host cell. These interactions bring the membrane surfaces into
mutual
proximity and allow for other surface glycoproteins to interact. Once
bound to
the HVEM, glycoprotein D changes its conformation and interacts with
glycoproteins H and L, which form a complex. The interaction of these
membrane
proteins results in the hemifusion state. Afterward, glycoprotein B
interaction
with the glycoprotein H and L complex creates an entry pore.
Glycoprotein B
interacts with host cell surface glycosaminoglycans. Genetic
inoculation After the viral
capsid enters the cellular cytoplasm,
it is transported to the cell nucleus. Once attached to the nucleus at
a
nuclear entry pore, the capsid ejects its DNA contents via the capsid
portal.
The capsid portal is formed by twelve copies of portal protein arranged
as a
ring; the proteins contain a leucine zipper sequence of amino acids
which allow
them to adhere to each other Each icosahedral capsid contains a single
portal,
located in one vertex. The DNA exits the capsid in a single linear
segment. Replication Consequent to a
cell being infected, groups of Herpes
virus proteins, termed immediate-early, early, and late proteins, are
produced
following specific time periods. Research using a new flow cytometry
methodology in KSHV indicates the possibility of an additional lytic
stage,
delayed-late. These stages of lytic infection, particularly late lytic,
are
distinct from the latency stage. For example, in the case of HSV-1, no
protein
products are detected during latency. The early
proteins transcribed are used in the
regulation of genetic replication of the virus. On entering the cell,
an α-TIF
protein joins the viral particle and aids in immediate-early
Transcription. The
virion host shutoff protein (VHF-UL41) is very important to viral
replication.
This enzyme shuts off protein synthesis in the host, degrades host
mRNA, helps
in viral replication, and regulates gene expression of viral proteins.
The
viral genome immediately travels to the nucleus but the VHF protein
remains in
the cytoplasm. The late
proteins transcribed are used in the capsid
formation and forming the receptors on the surface of the virus. The
packaging
of the viral particles, which include the genome, core and the capsid,
occur in
the nucleus. In the nucleus, cleavage of genome concatemers occurs and
these
are placed into pre-formed capsids. HSV-1 undergoes a process of
primary and
secondary envelopment. It aquires a primary envelope by budding into
the inner
nuclear membrane. This then fuses with the outer nuclear membrane
releasing a
naked capsid into the cytoplasm. The virus aquires its final envelope
by
budding into cytoplasmic vesicles. Latent infection HSV may persist
in a quiescent but persistent form
known as latent infection, notably in neural ganglia. During latent
infection
of a cell, HSV express Latency Associated Transcript (LAT) RNA. LAT is
known to
regulate the host cell genome and interferes with natural cell death
mechanisms. By maintaining the host cells, LAT expression preserves a
reservoir
for the virus, which allows later recurrences to produce further
infections. A protein found
in neurons may bind to Herpes DNA and
regulate latency. Recent studies have found that the Herpes DNA
contains a
sequence that is involved in silencing the expression of a gene
associated with
lytic infection, ICP4. The sequence contains elements which bind to
human nerve
cell protein factors: the human neuronal protein Neuronal Restrictive
Silencing
Factor (NRSF), and human Repressor Element Silencing Transcription
Factor
(REST). When the proteins are able to bind to the viral DNA elements,
histone
deacytalization occurs atop the ICP4 gene sequence. Reactivation The virus can
be reactivated due to the effects of
other illnesses such as cold and influenza, menstruation, emotional and
physical stress, exposure to bright sunlight, gastric upset, fatigue or
injury,
consequently resulting in the appearance of surface sores. Transmission Main article:
Herpes simplex HSV is
generally transmitted by direct contact of lips
or genitals when the sores are present, or when no sores are present
(known as
viral shedding). HSV can be present in semen, vaginal fluids, and
saliva. In
addition, herpes may be transmitted during childbirth, which can be
fatal to
the infant. The immature immune system of the child is unable to defend
against
the virus and even if treated, infection can result in brain damage.
Transmission occurs when passing through the birth canal and the risk
of
infection is minimal if there are no symptoms or exposed blisters
during
delivery. The first outbreak after exposure to HSV is commonly more
severe than
future outbreaks, as the body has not had a chance to produce
antibodies; this
first outbreak carries a low (~1%) risk of developing aseptic
meningitis. Human
papillomavirus Papillomaviruses
are a diverse group of DNA-based
viruses that infect the skin and mucous membranes of humans and a
variety of
animals. Over 100 different human papillomavirus (HPV) types have been
identified. Some HPV types
may cause warts while others may cause
a subclinical infection resulting in precancerous lesions. All HPVs are
transmitted by skin-to-skin contact. A group of
about 30-40 HPVs is typically transmitted
through sexual contact and infect the anogenital region. Some sexually
transmitted HPVs -- types 6, 11, may cause genital warts. However,
other HPV
types which may infect the genitals do not to cause any noticeable
signs of
infection. Persistent
infection with a subset of about 13
so-called "high-risk" sexually transmitted HPVs, including types 16,
18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 — different from the
ones
that cause warts — may lead to the development of cervical
intraepithelial
neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), penile
intraepithelial
neoplasia (PIN), and/or anal intraepithelial neoplasia (AIN). These are
precancerous lesions and can progress to invasive cancer. HPV infection
is a
necessary factor in the development of nearly all cases of cervical
cancer. A cervical Pap
smear with HPV DNA testing is used to
detect cellular abnormalities and the presence of HPV. This allows
targeted
surgical removal of condylomatous and/or pre-cancerous lesions prior to
the
development of invasive cervical cancer. Although the widespread use of
Pap
testing has reduced the incidence and lethality of cervical cancer in
developed
countries, the disease still kills several hundred thousand women per
year
worldwide. A recently approved HPV vaccine, Gardasil, that blocks
initial
infection with several of the most common sexually transmitted HPV
types may
lead to further decreases in the incidence of HPV-induced
cancer. Genital
HPV prevalence in the United States Quoted
statistics of HPV infection vary, with one
review finding reported values anywhere from 14% to 90%. The major
reason
numbers conflict is simply a lack of context. A report of the number of
women
that have ever been infected by any type will be much higher than the
number
that are currently infected by one of the high-risk types. The
confusion
surrounding the issue is highlighted by news coverage of a
comprehensive study
published in February 2007. Some headlines read "more women than
expected
have HPV", while others said that infection was "rarer than first
estimated". Both are actually true, in context: The study found
that, during 2003–2004, at any given
time, 26.8% of women aged 14 to 59 were infected with at least one type
of HPV.
This was higher than previous estimates. Of the four types prevented by
the
Gardasil vaccine, however, only 3.4% were infected, which was lower
than
previous estimates. Of the high-risk types that cause cancer, 15.2%
were
infected. In the year
2000, HPV infection accounted for
approximately 6.2 million of all sexually-transmitted diseases among
Americans
aged 15-44. It is estimated that 74% occurred to people between ages
15-24. Genital HPV
infection is very common, with estimates
suggesting that more than 50% of women will become infected with one or
more of
the sexually transmitted HPV types at some point during adulthood. The American
Social Health Association projections in
2006 were yet more pessimistic, predicting that about 75% of the
reproductive
population will have been infected with genital HPV infection in their
lifetime. Studies show that HPV infection is much more prevalent among
men who
have unprotected anal intercourse with other men. Studies show a link
between
HPV infection and penile and anal cancer, and the risk for anal cancer
is 17 to
31 times higher among men who have had receptive anal intercourse than
among
men who have not. Although it is
possible to test for HPV DNA in men,
there are no FDA-approved tests for general screening, since the
testing is
inconclusive and considered medically unnecessary. There is no screening test for HPV infection in men. However, although there are no formal guidelines, some experts believe that men who receive anal sex should have a routine anal Pap test, especially if they also have HIV infection. Ask your health professional whether and how often you should be tested. back to topLeishmaniasis Most forms of
the disease are transmissible only from
animals (zoonosis), but some can be spread between humans. Human
infection is
caused by about 21 of 30 species that infect mammals. These include the
L.
donovani complex with three species (L. donovani, L. infantum, and L.
chagasi);
the L. mexicana complex with 3 main species (L. mexicana, L.
amazonensis, and L.
venezuelensis); L. tropica; L. major; L. aethiopica; and the subgenus
Viannia
with four main species (L. (V.) braziliensis, L. (V.) guyanensis, L.
(V.)
panamensis, and L. (V.) peruviana). The different species are
morphologically
indistinguishable, but they can be differentiated by isoenzyme
analysis, DNA
sequence analysis, or monoclonal antibodies. Visceral
leishmaniasis is a severe form in which the
parasites have migrated to the vital organs. Citation
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