Retrovirus in Disease-HIV
Human immune deficiency virus (HIV) is a retrovirus that primarily infects vital components of the human immune system.
Discovery of HIV
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HIV was discovered by scientists led
by Luc Montagnier at the Pasteur Institute in
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HIV originated in west and central
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It is possible that HIV entered the human
population in the 1930’s.
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The most severe manifestation of infection
with HIV is AIDS.
Virus Classification
Ø Group: Group VI (ssRNA-RT)
Family: Retroviridae
Genus: Lentivirus
Species: Human immunodeficiency virus 1
Species: Human immunodeficiency virus 2
HIV is a part of the genus lentivirus, lentiviruses infect many species and are transmitted as a single stranded enveloped RNA viruses. Lentiviruses are responsible for long duration illnesses associated with long term incubation. There are two species of HIV that humans are susceptible to HIV-1 and HIV-2. HIV-1 is more virulent and easily transmitted and this the main source of HIV infections in the world’s population. HIV-2 is mainly restricted to west Africa.
Transmission of HIV
Ø HIV can be transmitted by exposure to cellular fluids
1) Blood exposure
a) Blood transfusion
b) Needle stick with HIV contaminated needle
c) Needle sharing injection drug use
d) Blood to blood contact
2) Semen
a) Unprotected sexual contact
3) Vaginal Secretions
a) Unprotected sexual contact
4) Mother to child
a) Breast milk
b) Childbirth
HIV Structure
HIV is approximately 60 times smaller than a red blood cell and is roughly spherical. HIV-1 is made of two copies of a single stranded RNA enclosed in a conical capsid, which is surrounded by a plasma membrane that is formed from a part of the host-cell membrane, and contains enzymes such as reverse transcriptase, integrase, and protease.
Structural elements in HIV
1) Gag gene- provides physical infrastructure of the virus.
2) Pol gene- provides the basic enzymes that help retroviruses reproduce.
3) Env gene- supplies the proteins fundamental for viral attachment and entry into a target cell. The glycoproteins gp120 and gp41 are both encoded by the env gene
4) Accessory proteins- (tat, rev, vif, vpr, vpu)-enhance virus production.
HIV invasion of a target cell
Ø
HIV infects cells such as CD4+ helper
T-cells and macrophages, which are present in the immune system.
Ø
The gp120 binds to the CD4 molecules
on the target cell and then enter the target cell carrying the CD4 marker.
The virus’s chemokine coreceptors, such as CCR5 in macrophage strains of
HIV-1, are also used to gain entry into the target cell.
Ø The CD4 receptor provokes changes in gp120 that exposes a region of the gp120 that binds to a cytokine receptor on the target cell. This change in the gp120 exposes a portion of the gp41 protein that was buried in the viral membrane and loosely bound to gp120. The gp41 protein causes fusion of the viral envelope and the host cell envelope, allowing the HIV capsid to enter the target cell.
Figure 2. HIV binding via cell surface receptors. (http://webs.wichita.edu/mschneegurt/biol103/lecture15/lecture15.html)
Replication and Transcription
of HIV
Ø
The capsid enters the cell and reverse
transcriptase releases the single stranded RNA from the attached viral proteins
and copies it into a complementary DNA strand.
Then the reverse transcriptase makes another complementary DNA strand to
form a double stranded viral DNA intermediate. Reverse transcription is error prone
and is where mutations are probable to ocuur, such as drug resistance.
The integrase enzyme is used to carry out the integration of the new DNA
into the cell nucleus.
Ø
To actively produce the virus, transcription
needs to occur.
Transcription- the process of constructing a messenger RNA molecule using a DNA molecule as a template with resulting transfer of genetic information to the messenger RNA.
Ø This mRNA is then transported out of the cell nucleus into the cytoplasm, where translation occurs.
Translation- the process of forming a protein molecule at a ribosomal site of protein synthesis from information contained in messenger RNA.
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The protein is then cleaved by the enzyme
protease. Then the reconstruction of
a new virus is underway.
Figure 3. The
HIV replication Cycle (1).
Treatment
There is currently no cure for HIV infection but there are ways to treat HIV infection.
Anitretroviral Drugs
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Reverse transcriptase inhibitors- such as the most common
used drugs to treat HIV- AZT(Azidothymidine) and 3TC
Ø Protease inhibitors
Ø Fusion inhibitors-block HIV from fusing with a cell’s membrane
Ø Integrase inhibitors
Synergistic Enhancers
Synergistic enhancers are substances that don’t necessarily have any antiretroviral properties, but when paired with antiretroviral drugs they can improve the effects of that drug.
Ø Hydroxyurea- an older medication that is used to treat hematologic disorders.
Ø Resveratrol and Grapefruit juice- a natural extract of plants
Ø Mycophenolic acid- an inosine monophosphate dehydrogenase inhibitor
Ø Ritonavir- enhances protease inhibitors
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Leflunomide- enhances AZT
Figure 4 HIV Drug Cylce.
http://webs.wichita.edu/mschneegurt/biol103/lecture15/lecture15.html
Other Diseases Caused by Retroviruses
Ø Sarcoma
Ø Osteosarcoma
Ø Myelocytoma
Ø Pre-B cell leukemia
Ø Feline leukemia
References
1)
HIV. (2006,March 25). In Wikipedia:
The free encyclopedia. Retrieved March 25, 2006, from
http://en.wikipedia.org/wiki/HIV
2) Flaskerud, Jacquelyn. AIDS/HIV INFECTION A REFERENCE GUIDE FOR NURSING PROFESSIONALS. Phikadelphia, W.B SAUNDERS COMPANY. 1989. PP 37-44.
3)
Roitt, Ivan. Ed. Brostoff, Jonthan, etal. IMMUNOLOGY.4th ed.
4) (http://webs.wichita.edu/mschneegurt/biol103/lecture15/lecture15.html)
5)
Antiretroviral Drugs. (2006,March 25).
In Wikipedia: The free encyclopedia. Retrieved March 25, 2006, from
http://en.wikipedia.org/wiki/Antiretroviral_drugs