● $BlogItemTitle$> @ Tuesday, December 16, 2008 ●
Lecture 5!
Retrovirus
1) Properties of Retroviruses
= Reverse transcriptase
- Genome does not serve as mRNA
= Formation of long terminal repeats before provirus DNA is inserted into host genome
= gag, pol, env genes some regulatory genes and some oncogenes (mutated form of cellular genes)
2) Retroviral genes
= gag
- Group-specific antigen
- Virion core (capsid protein)
- codes for core structural proteins of a retrovirus
= pol
- Polymerase (reverse transcriptase)
- RNase H
- codes for reverse transcriptase, protease and intergrase
= env
- envelope
- codes for retroviral coat proteins
3) Types and structure
= Tumour-forming
- transducing
- cis-activating
- Trans-activating (HTLV) >
= Non-tumour forming
- Lentiviruses
- HIV >
RETROVIRUSES are about 80-100nm across, which means they are so small that they can only be seen with an electron microscope.
The structure consists of a flexible outer membrane called the envelope which is studded with glycoproteins peplomers, chemical receptors that enable the virus to attach to cells. It is surrounded by a protein case known as the capsid.
The capsid’s hollow interior contains two identical strands of RNA, which makes up the virus’s genetic program and stores instructions needed for replication upon infecting a host cell. Retroviruses also contain molecules of an enzyme called reverse transcriptase. When a virus infects a cell, reverse transcriptase copies the genetic instructions in the virus’s RNA and uses it to build complementary strands of DNA. It has a 3' polyadenylated tail and 5' cap.
4) HTLV-1
= Adult T-cell leukemia / lymphoma (ATLL)
- Acute aggressive luekemia resulting in death in 12 months. It has no known cure yet.
= Tropical spastic paraparesis / HTLV-1 associated myelopathy
- Wasting of neurons (loss of myelin sheaf, a insulating envelope of myelin that surrounds the core of a nerve fiber or axon and facilitates the transmission of nerve impulses)
5) HIV Life cycle
5.1= Binding and Fusion:
The HIV virus first binds to a CD4 receptor and one of two co-receptors on the surface of a CD4+ T- lymphocyte and fuses with the host cell. After fusion, the virus releases RNA into the host cell.
5.2= Reverse Transcription:
An enzyme called reverse transcriptase converts the single-stranded HIV RNA to double-stranded HIV DNA.
5.3= Integration:
The newly formed HIV DNA enters the host cell's nucleus, where an enzyme called integrase "hides" the HIV DNA within the host cell's own DNA. The integrated HIV DNA is called provirus and may remain inactive for several years, producing few or no new copies of HIV.
5.4= Transcription:
When the host cell receives a signal to become active, the provirus utilises RNA polymerase, a host enzyme to create copies of the HIV genomic material and shorter strands of RNA called messenger RNA (mRNA), which would then be used as a blueprint to make long chains of HIV proteins.
5.5= Assembly:
An enzyme called protease then cuts the long chains of HIV proteins into smaller individual proteins. As the smaller HIV proteins are assembled with copies of HIV's RNA genetic material, a new virus particle is assembled.
5.6= Budding:
The newly assembled virus forms a "bud" on the host cell and makes its way out. During budding, the new virus steals part of the cell's outer envelope, which acts as a covering and has protein/sugar combinations called HIV glycoproteins on it. These glycoproteins are necessary for the virus binding to CD4 and its co-receptors. The new copies of HIV can now move on to infect other cells.
6) AIDS transmission
= Sexual contact
= Blood and blood products
= Other body fluids
= Mother to child
- Placenta
- Mucosa
- Breast milk
=Pandemic
7) Category
= Retroviridae
- Alpharetrovirus
- Betaretrovirus
- Gammaretrovirus
- Deltaretrovirus
- Epsilonretrovirus
- Lentivirus
- Spumavirus
8) Pathogenesis
= Primary infection
- Acute stage
- Flu-like symptoms
- Fever
- Skin rash
- Swollen lymph nodes
- Virulence factors
- Rate of replication
- Propensity to mutate
- Cytopathogenicity
- Host resistance
- Suppression by CD8 T suppressor cells
- Presence of cytotoxic T-lymphocytes
= Asymptomatic stage
- No apparent disease but with falls in CD4 T lymphocytes (primary target cell)
-Possible signs inculde: 1. Fatigue 2. Depression 3. Weight loss 4. Memory disorders
= Symptomatic stage
- AIDS-related complex
- Diseases not considered definitive of AIDS but may be attributed to HIV infection
- Indicative of defect in cell-mediate immunity
- AIDS
- Opportunistic infections as a result of fall in CD4 T lymphocytes
9) AIDS therapy
= Non-specific therapeutic management
- To boost general health
- Vitamins, minerals, anti-oxidants and others
= Specific therapeutic management: antiretroviral therapy
- Nucleoside Reverse Transcriptase Inhibitors :
- AZT (azidothymidine)
- 3TC (lamivudine)
- Non-nucleoside Reverse Transcriptase Inhibitors
= Immunomodulation (enhancement of immune system through treatment with Interleukin-2)
= Vaccines (no successful discovery of vaccine yet)
10) Antiretroviral therapy
= Protease inhibitors
= Rapid mutations due to inefficiency of reverse transcriptase
= Combination therapy to combat resistance
References:
http://encarta.msn.com/encnet/refpages/RefArticle.aspx?refid=761561203
http://www.answers.com/topic/myelin-1
http://en.wikipedia.org/wiki/Retrovirus
http://www.aidsinfo.nih.gov/contentfiles/HIVLifeCycle_FS_en.pdf