Week 3 Retrovirus Flashcards
RNA viruses
What are the 4 main types, give examples of each
•Double-stranded positive sense RNA viruses
–e.g. rotavirus
•Single-stranded positive sense RNA viruses
–e.g. polio
•Single-stranded negative sense RNA viruses
–e.g. influenza, rabies
•RETROVIRUSES Diploid positive sense RNA
–Unique enzyme – reverse transcriptase - which generates a DNA intermediate which is then integrated into the host genome (called provirus)
–New viral genomes produced by cellular transcriptional machinery
–e.g. HIV
Genomic organisation of retroviruses
What is the gene order of retroviruses?
What does gag code for?
What does pol code for?
What does env code for?
Genomic organisation of retroviruses
Gene order in all retroviruses is invariant: 5’ - gag - pol - env - 3’
Gag – codes for proteins which make up the matrix, capsid, and nucleoprotein structures
Pol - codes for reverse transcriptase and integrase and protease enzymes
Env - codes for the surface and transmembrane components of the viral envelope protein (Env)
Life cycle of the retrovirus:
What is the principle difference between retrovirus and influenza life cyle?
Principle differences with the retrovirus is: reverse transcription, the production of DNA and the integration of the DNA into the chromosome
How does reverse transcriptase work?
What is the viral RNA genome convereted into?
RNA is transcribed by a virus-associated reverse transcriptase which converts the viral RNA genome to a DNA-RNA hybrid.
RNA strand is digested away and replaced by a DNA copy to give a double stranded (ds) DNA molecule.
When integrated into the host genome this is called the provirus
CELL WALL PROTEIN of VRION receptor binding protein (gp-120-gp41)
What are teh key enzymes of retroviruses?
What is the role of reverse transcriptase
What is the role of integrase?
What is the role of protease?
Reverse transcriptase – transcription of viral genome RNA to DNA
Integrase – integration of the ds DNA into the host genome to form the provirus
Protease – following release of new virion, cleavage of certain proteins is required for viral maturation and infectivity
Retroviral structure
What does it inherit from the host cell, is this similar to influenza?
Lipid membrane is inherited from the host genome which is similar to the process in influenza.
Transmembrane inherited from the host which clearly gives it an advantage when avoiding immune surveillance by the host.
What are the two forms of retroviruses?
Two forms of retroviruses exist:
- Oncovirinae
- Lentivirinae
Discovery of the first human retrovirus
Clusters of adults suffered from ?
Isolation of retrovirus from lymphocytes of one of the patients
What was it named?
•Cluster of cases adult T-cell leukaemia in the southern islands of Japan
•Clustering made scientists suspicious that an infectious agent was involved in the pathogenesis
•In 1978 Robert Gallo in the U.S. isolated a retrovirus from the lymphocytes from these patients
–it was named Human T-cell Leukaemia Virus type 1 (HTLV-1)
•It proved to be endemic not only in southern Japan but also in parts of Central and South America, the Caribbean and Africa.
What was the receptor of HTLV?
Where is HTLV infection found?
Where is HTLV-2 found?
The receptor for HTLV is the Glut-1 receptor
HTLV infection is worldwide: Japan, Central and South Africa, Melanesia, South America, Caribbean
HTLV-2 some native South American and Caribbean groups, I.V. drug users in the U.S.
Human T-cell Lymphotropic Virus (HTLV)
HTLV-1
What is the cause?
What affect does it have?
- causative agent of Adult T-cell leukemia: A clonal aggressive malignancy of CD4+ T lymphocytes
HTLV-1 Associated Myelopathy (HAM) and Tropical Spastic Paraparesis (TSP):
Chronic and progressive disease of the nervous system causes progressive weakness, stiff muscles, muscle spasms, sensory disturbance, and sphincter dysfunction
HTLV-2 associated disease
What is it linked with?
What is the latency period?
•HTLV-2
- linked with sporadic cases of myelopathy resembling
HAM/TSP
- Hairy Cell Leukemia
•Long latency periods of 20 – 30 years
HTLV-2 causes
Hairy Cell Leukemia
Where do the leukemia cells collect?
- Leukemia cells collect in the spleen and the spleen swells•There also may be too few normal white blood cells in the blood because the leukemia cells invade the bone marrow
- The marrow cannot produce enough normal white blood cells. This can result in a decreased resistance to infections
HTLV Transmission
requires ?
What percentage is mother-to-child?
mother-to-child: 15-20% of breast fed children of HTLV-I seropositive mothers
get infected, unprotected sex, contaminated blood products
Retrovirus:
Lentitvirinae
What does it include?
Lentitvirinae: long latency includes HIV-1 and HIV-2
By the end of 2011, an estimated 96,000 people were living with HIV in the UK, 73,400 people diagnosed with HIV and 22,600 who did not know they were infected.
Where is HIV-1 M from?
Where is HIV-1 O from?
Where is HIV-2 from?
HIV-1 M: Pan troglodytes, chimpanzee (western Africa)
HIV-1 O: Gorilla,
HIV-2: Cercocebus atys, sooty mangabey