HELLO

Sunday, February 1, 2009

Retroviruses

There are two types of Retroviruses:
1. Tumour forming
§ Transducing
§ Cis-activating
§ Trans-activating ( HTLV)
2. Non- tumour-forming
§ Lentiviruses
§ HIV

The focus on the content will be on HTLV-1 and HIV.

HTLV-1
Adult T-cell leukaemia/lymphoma (ATLL)
+ Acute aggressive leukaemia resulting in death in 12 months
+ There are no known cure yet
Tropical spastic Paraparesis / HTLV-1 associated myelopathy
+ Wasting of neurons (lost of myelin sheaf)
+ Back pain followed by paralysis

HIV

Pathogenesis of HIV

Untreated HIV disease is characterized by a gradual deterioration of immune function. Most notably, crucial immune cells called CD4 positive (CD4+) T cells are disabled and killed during the typical course of infection. These cells, sometimes called “T-helper cells,” play a central role in the immune response, signaling other cells in the immune system to perform their special functions.
A healthy, uninfected person usually has 800 to 1,200 CD4+ T cells per cubic millimeter (mm3) of blood. During untreated HIV infection, the number of these cells in a person’s blood progressively declines. When the CD4+ T cell count falls below 200/mm3, a person becomes particularly vulnerable to the opportunistic infections and cancers that typify AIDS, the end stage of HIV disease. People with AIDS often suffer infections of the lungs, intestinal tract, brain, eyes, and other organs, as well as debilitating weight loss, diarrhea, neurologic conditions, and cancers such as Kaposi’s sarcoma and certain types of lymphomas.

Primary Infection
§ Acute stage
§ Flu-like symptoms
§ Fever
§ Skin rash
§ Swollen lymph nodes
§ Virulence factors
+ Rate of replication
+ Propensity to mutate
+ Cytopathogenicity
§ Host resistance
+ Suppresion by CD8 T suppressor cells
+ Presence of cytotoxic T-lymphocytes

Asymptomatic Stage
· No apparent disease
· Fall in CD4 T lymphocytes ( primary target cell)
· Possible signs ( fatigue , depression, weight loss, memory disorders)

HIV attachment

Attachment of HIV to a CD4+ cell. The outer domain of gp120 binds to the CD4 antigen. This leads to a conformational change in gp120 and a co-receptor binding site is exposed. This region of gp120 binds to the chemokine receptor. Binding to the chemokine receptor allows another conformational change to occur so that regions of the gp41 HIV protein interact to form a fusion domain that allows the viral and cell membrane to fuse.

HIV life cycle

View this link for further explanation and larger image:
http://www.aidseducator.org/FactSheets/106-HIV-Life-Cycle.html

Videos:

HIV virus

AIDS

AIDS- transmission
· Sexual contact
· Blood and blood products
· Mother to child
- Placenta
- Mucosa
- Breast milk
· Pandemic

Symptomatic Stage

There are 4 stages:

Stage 1: Primary HIV Infection
The first stage of HIV infection is called primary infection. Primary infection begins shortly after an individual first becomes infected with HIV. This stage lasts for a few weeks. During this time period, individuals experience symptoms similar to the flu. Very few individuals seek treatment during this time, and those who do are usually misdiagnosed with a viral infection.
Often, if an HIV test is performed, it will come back negative, since antibodies are not yet being produced by the individual’s immune system. Those who believe they have been exposed to HIV should repeat the test again after six months.

Stage 2: Asymptomatic HIV
In the second stage, individuals are free from any symptoms of HIV. Levels of HIV in the blood are very low, but are detectable. If an HIV test is performed, it will come back positive. While the individual is asymptomatic, the HIV in their blood is reproducing constantly. This stage lasts about ten years, but can be much longer or shorter depending on the individual.

Stage 3: Symptomatic HIV
In the third stage, the immune system has become so damaged by HIV that symptoms begin to appear. Symptoms are typically mild at first, and then slowly become more severe. Opportunistic infections, infections that take advantage of the immune system’s vulnerable state, begin to occur. These infections affect almost all the systems of the body and include both infections and cancers. Some common opportunistic infections include tuberculosis, cytomegalovirus, and shingles.

Stage 4: Acquired Immune Deficiency Syndrome
In the fourth and final stage, a person is diagnosed as having AIDS. To be diagnosed as having AIDS, a person has to exhibit certain opportunistic infections, such as HIV wasting syndrome, pneumocystis pneumonia, or Kaposi sarcoma. Once a person is diagnosed with AIDS, they can never return to a stage of HIV, even if the individual gets better.

AIDS-related complex
- Diseases not considered definitive of AIDS
- May be attributed to HIV infection
- Indicative of detect in cell-mediate
- Immunity

AIDS
- Opportunistic infections as a result of fall in CD4 lymphocytes

AIDS therapy
Non-specific therapeutic management
- To boost general health
- Vitamins
- Minerals
- Anti-oxidants
- Others

Specific therapeutic management:
- Antiretroviral therapy

Nucleoside Reverse transcriptase Inhibitors:
-AZT (azidothymidine)
-3TC (lamivudine)

Non-nucleoside Reverse Transcriptase Inhibitors
-Efavirenz
-Nevirapine
*Rapid mutations due to inefficiency of reverse transcriptase

Vaccines
-Many candidates under development and trails.
-None so far proven useful

Video:

How HIV become Aids.

HELLO

4:04 AM