Posted by
Savannah Momo on Monday, January 25, 2010 9:18:49 PM
HIV is a member of the genus Lentivirus, part of the family of
Retroviridae. Lentiviruses have many common morphologies and biological
properties. Many species are infected by lentiviruses, which are
characteristically responsible for long-duration illnesses with a long
incubation period. Lentiviruses are transmitted as single-stranded,
positive-sense, enveloped RNA viruses. Upon entry of the target cell,
the viral RNA genome is converted to double-stranded DNA by a virally
encoded reverse transcriptase that is present in the virus particle.
This viral DNA is then integrated into the cellular DNA by a virally
encoded integrase, along with host cellular co-factors, so that the
genome can be transcribed. After the virus has infected the cell, two
pathways are possible: either the virus becomes latent and the infected
cell continues to function or the virus becomes active and replicates,
and a large number of virus particles that can then infect other cells
are liberated.
There are two species of
HIV known to exist:
HIV-1 and
HIV-2 .
HIV-1 is the virus that was initially discovered and termed LAV. It is
more virulent, more infective, and is the cause of the majority of HIV
infections globally. The lower infectivity of HIV-2 compared to HIV-1
implies that fewer of those exposed to HIV-2 will be infected per
exposure. Because of its relatively poor capacity for transmission,
HIV-2 is largely confined to West Africa.
Infection with HIV-1 is associated with a progressive decrease of the
CD4+ T cell count and an increase in viral load. The stage of infection
can be determined by measuring the patient's CD4+ T cell count, and the
level of HIV in the blood.
HIV infection has basically four stages: incubation period, acute
infection, latency stage and AIDS. The initial incubation period upon
infection is asymptomatic and usually lasts between two and four weeks.
The second stage, acute infection, which lasts an average of 28 days
and can include symptoms such as fever, lymphadenopathy (swollen lymph
nodes), pharyngitis (sore throat), rash, myalgia (muscle pain),
malaise, and mouth and esophageal sores. The latency stage, which
occurs third, shows few or no symptoms and can last anywhere from two
weeks to twenty years and beyond. AIDS, the fourth and final stage of
HIV infection shows as symptoms of various opportunistic infections.
A study of French hospital patients found that approximately 0.5% of
HIV-1 infected individuals retain high levels of CD4 T-Cells and a low
or clinically undetectable viral load without anti-retroviral
treatment. These individuals are classified as HIV controllers or
Long-term nonprogressors.
The initial infection with HIV generally occurs after transfer of body
fluids from an infected person to an uninfected one. The first stage of
infection, the primary, or acute infection, is a period of rapid viral
replication that immediately follows the individual's exposure to HIV
leading to an abundance of virus in the peripheral blood with levels of
HIV commonly approaching several million viruses per mL. This response
is accompanied by a marked drop in the numbers of circulating CD4+ T
cells. This acute viremia is associated in virtually all patients with
the activation of CD8+ T cells, which kill HIV-infected cells, and
subsequently with antibody production, or seroconversion. The CD8+ T
cell response is thought to be important in controlling virus levels,
which peak and then decline, as the CD4+ T cell counts rebound to
around 800 cells per µL (the normal blood value is 1200 cells per µL ).
A good CD8+ T cell response has been linked to slower disease
progression and a better prognosis, though it does not eliminate the
virus.
During this period (usually 2–4 weeks post-exposure) most individuals
(80 to 90%) develop an influenza or mononucleosis-like illness called
acute HIV infection, the most common symptoms of which may include
fever, lymphadenopathy, pharyngitis, rash, myalgia, malaise, mouth and
esophagal sores, and may also include, but less commonly, headache,
nausea and vomiting, enlarged liver/spleen, weight loss, thrush, and
neurological symptoms. Infected individuals may experience all, some,
or none of these symptoms. The duration of symptoms varies, averaging
28 days and usually lasting at least a week. Because of the nonspecific
nature of these symptoms, they are often not recognized as signs of HIV
infection. Even if patients go to their doctors or a hospital, they
will often be misdiagnosed as having one of the more common infectious
diseases with the same symptoms. As a consequence, these primary
symptoms are not used to diagnose HIV infection, as they do not develop
in all cases and because many are caused by other more common diseases.
However, recognizing the syndrome can be important because the patient
is much more infectious during this period.
A strong immune defense reduces the number of viral particles in the
blood stream, marking the start of the infection's clinical latency
stage. Clinical latency can vary between two weeks and 20 years. During
this early phase of infection, HIV is active within lymphoid organs,
where large amounts of virus become trapped in the follicular dendritic
cells (FDC) network. The surrounding tissues that are rich in CD4+ T
cells may also become infected, and viral particles accumulate both in
infected cells and as free virus. Individuals who are in this phase are
still infectious. During this time, CD4+ CD45RO+ T cells carry most of
the proviral load.
When CD4+ T cell numbers decline below a critical level of 200 cells
per µL, cell-mediated immunity is lost, and infections with a variety
of opportunistic microbes appear. The first symptoms often include
moderate and unexplained weight loss, recurring respiratory tract
infections (such as sinusitis, bronchitis, otitis media,
pharyngitis),prostatitis, skin rashes, and oral ulcerations. Common
opportunistic infections and tumors, most of which are normally
controlled by robust CD4+ T cell-mediated immunity then start to affect
the patient. Typically, resistance is lost early on to oral Candida
species and to Mycobacterium tuberculosis, which leads to an increased
susceptibility to oral candidiasis(thrush) and tuberculosis. Later,
reactivation of latent herpes viruses may cause worsening recurrences
of herpes simplex eruptions, shingles, Epstein-Barr virus-induced
B-cell lymphomas, or Kaposi's sarcoma. Pneumonia caused by the fungus
Pneumocystis jirovecii is common and often fatal. In the final stages
of
AIDS ,
infection with cytomegalovirus (another herpes virus) or Mycobacterium
avium complex is more prominent. Not all patients with AIDS get all
these infections or tumors, and there are other tumors and infections
that are less prominent but still significant.