A retrovirus is a virus with an RNA genome that replicates by using a viral reverse transcriptase enzyme to transcribe its RNA into DNA in the host cell.
The DNA is then incorporated into the host's genome by an integrase enzyme.
The virus thereafter replicates as part of the host cell's DNA. Retroviruses are enveloped viruses that belong to the viral family Retroviridae.
Description of virus
The virus itself stores its nucleic acid, in the form of a +mRNA genome and serves as a means of delivery of that genome into cells it targets as an obligate parasite, and constitutes the infection.
Once in the host's cell, the RNA strands undergo reverse transcription in the cytosol and are integrated into the host's genome, at which point the retroviral DNA is referred to as a provirus.
It is difficult to detect the virus until it has infected the host.
Virion Structure
The main virion components are:
• Envelope: lipid bilayer which obtained from host plasma membrane
• RNA
• Proteins: consisted of gag proteins, protease (PR), pol proteins and env proteins.
Gag proteins are major components of the viral capsid which are about 2000-4000 copies per virion. Protease, on one hand, is expressed differently in different viruses.
It functions in proteolytic cleavages during virion maturation to make mature gag and pol proteins. Pol proteins are responsible for synthesis of viral DNA and integration into host DNA after infection.
Finally, env proteins play role in association and entry of virion into the host cell.
Properties:
It is a spherical virion and has a ribonucleoprotein in central nucleoid within icohedral capsid.
It has an envelope with glycoprotein peplomers and has 2 copies of linear (+) sense ssRNA.
The virus have a 3’ polyadenylated tail and 5’ cap and has the enzyme reverse transcriptase which reverse transcribe the viral RNA to DNA.
The virus will form long terminal repeats before provirus DNA is being inserted into host genome.
Gag, pol, env genes, some regulatory genes and some oncogenes are present in the virus.
Multiplication
When retroviruses have integrated their own genome into the germ line, their genome is passed on to a following generation.
While transcription was classically thought to only occur from DNA to RNA, reverse transcriptase transcribes RNA into DNA.
The term "retro" in retrovirus refers to this reversal (making DNA from RNA) of the central dogma of molecular biology.
These inserts are transcriped by host's enzymes into new RNA molecules which enter the cytosol. Next, some of these RNA molecules are translated into viral proteins. For example, the gag gene is translated into molecules of the capsid protein, the pol gene is transcribed into molecules of reverse transcriptase, and the env gene is translated into molecules of the envelope protein.
It is important to note that a retrovirus must "bring" its own reverse transcriptase in its capsid, otherwise it is unable to utilize the infected cell's enzymes to carry out the task, due to the unusual nature of producing DNA from RNA.
Because reverse transcription lacks the usual proofreading of DNA replication, a retrovirus mutates very often.
This enables the virus to grow resistant to antiviral pharmaceuticals quickly, and impedes the development of effective vaccines and inhibitors for the retrovirus.
Genes
Retrovirus genomes commonly contain three open reading frames that encode for proteins that can be found in the mature virus:
• group-specific antigen (gag) codes for core and structural proteins of the virus;
• polymerase (pol) codes for reverse transcriptase, protease and integrase; and,
• envelope (env) codes for the retroviral coat proteins.
Provirus
This DNA can be incorporated into host genome as a provirus that can be passed on to progeny cells. In this way some retroviruses can convert normal cells into cancer cells. Some provirus remains latent in the cell for a long period of time before it is activated by the change in cell environment.
Seven subfamilies
Subfamily: Orthoretrovirinae
- Alpharetrovirus
- Betaretrovirus
- Gammaretrovirus
- Deltaretrovirus
- Epsilonretrovirus
- Lentivirus
Subfamily: Spumaretrovirinae
- Spumavirus
Lets look at Human Immunodeficiency Virus (HIV), a type of Lentivirus.
Transmission
HIV can be transmitted via sexual contact, through blood and blood products and secretion of other bodily fluids like semen and vaginal secretion.
A mother can pass HIV to a child via the placenta, mucosa and breast milk.
Primary infection
During the acute stages, flu-like symptoms, fever, skin rash and swollen lymph nodes may be observable.
Virulence factors include rate of replication, propensity of mutate and cytopathogenicity.
The host immune system can reisist infection via supression by CD8 T supressor cells and presence of cytotoxic T-lymphocytes.
Asymptomatic stage
During asymptomatic stage, there is no apparent disease. But there will be a fall in CD4 T lymphocytes (primary target cells).
Possible signs includes fatigue, depression, weight loss and memory disorder.
Symptomatic stage
AIDS-related complex will occur. They are diseases not considered difinitive of AIDS but may be attributed to HIV infection. It is a indication of defects in cell-mediate immunity.
Opportunistic infections as a result of fall in CD4 T lymphocytes in AIDS patients.
Therapy
Non-specific therapeutic management is used to boost general health. This includes vitamins, mineral, antioxidants and others.
Specific therapeutic management involves in antiretroviral therapy like:
• Neucleoside reverse transcriptase inhibitors includes AZT (azidothymidine) and 3TC (lamivudine)
• Non-nucleoside reverse transcriptase inhibitors includes Efavirenz and Nevirapine
• Protease inhobitors include Indinavir and Ritonavir
The inefficiency of reverse transcriptase causes the virus to rapidly mutate.
A combine therapy is used to combat resistance.
Immunomodulation include enhancement of immune system through treatment with potential drugs that are still under study.
Vaccines that are still under development.
Diseases
Diseases that can occur in AIDS patients includes Kaposi’s Sarcoma, Oral Hairy Leukoplakia and Candidiasis.
Done by: Jeremy Lee