Retroviruses Flashcards
What do normal RNA viruses contain?
- double stranded RNA positive
- single strand RNA negative
What distinguishes retroviruses?
- diploid positive sense RNA
- contain reverse transcriptase which generates DNA which is integrated into host genome
Main example of a retrovirus
HIV
What is the life cycle of a retrovirus?
- virus binds to specific receptor on cell surface
- double strand RNA enters cell
- changes to DNA by reverse transcriptase
- DNA in nucleus integrates into host DNA
- millions of copies of virus can be made, proteins made
- proteins assemble at cell surface
- virus efflux picking up coat of bilayer
What is the receptor which HIB binds to?
CD4
Features of the retrovirus structure
- surface envelope (binding to target cell surface)
- matrix (holds virus shape)
- capsid inside matrix containing RNA to make copies of itself
- lipid envelope
- protease
- reverse transcriptase
What do accessory proteins do?
Interact with host innate immune response to viral infections counteracting it
What is the key enzyme!!! What does it do???
Reverse transcriptase - transcription of viral RNA to DNA
What does integrase do?
Integration of ds DNA into host genome to form provirus
What does protease do?
After new virion release, cleaves certain proteins for viral maturation and infectivity
What are the 2 groups of retroviruses?
Oncovirinae - induce oncogenesis causing tumours
Lentivirinae
What are some examples of oncovirinae?
RSV (rous sarcoma virus)
HTLV-1 (human T cell lymphotropic virus, first to be discovered)
HTLV -2
What does the genome of retroviruses consist of?
Gag, Pol, Env (structural genes)
Plus accessory proteins
Regulatory genes
How widespread is HTLV?
Southern Japan (via Portuguese explorers who had been in Africa)
Central America (slave trade reached)
South America (slave trade)
Africa where it originated in ancient times
Caribbean
15-20 million people
How is HTLV is transmitted?
- prolonged breast feeding mother to child
- sexual contact
- blood transfusion
How common are the different types of HTLV?
1 is most common, 4 is least
What does HTLV1 cause?
Adult T cell leukaemia
HTLV1 associated myelopathy
Tropical Spastic Paraparesis
What is the latency period of HTLV1?
20-30 years
Long
What is TSP? How does it present?
Tropic Spastic Paraparesis
- chronic
- progressive
- nervous system disease
- weakness, stiff muscles, muscle spasms, sensory disturbances, sphincter dysfunction
- affects adults in equatorial regions
How is TSP treated?
- high dose of IV methylprednisolone and daily prednisolone
What is adult T cell leukaemia?
Clonal aggressive malignancy of CD4+ T lymphocytes
- skin can be involved
How is adults T cell leukaemia treated?
- chemotherapy often ineffective
- ongoing trials (IFNalpha)
What does HTLV2 cause?
- HAM/TSP
- hairy cell leukaemia
What is the long latency of HTLV2?
Longer than HTLV1
20-30 years
What is hairy cell leukaemia?
- leukaemia cells collect in spleen
- spleen swells
- few normal WBCs as leukaemia invades bone marrow
= reduced infection resistance
How is HTLV transmission different from HIV transmission?
- requires cell to cell contact
What are some examples of lentivirinae?
HIV-1
HIV-2
How widespread is HIV?
- over 70 million people infected
- main epidemic is HIV1 in West Africa
- from chimpanzees to human
How is HIV transmitted?
- unprotected sexual intercourse with infected partner
- vertical transmission mother to child (in utero, during delivery or via breastmilk)
- injection drug use
What does HIV require to infect cells?
- both CD4 and chemokine receptor (CXCR4 or CCR5)
to be expressed by cells
What is the course of HIV infection?
- first 3 weeks virus multiplies lots and CD4 cell target cell decline
- immune system takes control and increases CD4 and reduces viral load (clinical latency where individual is unaware of infection)
- CD4 declines further and viral load increases (opportunistic infections)
What are the opportunistic infections of HIV?
- oral candidiasis
- interstitial pneumonia
What is a clade?
- related virus from a common ancestor (shows how diverse the virus is)
- HIV has many clades so is very diverse vs. measles for example
- Clade B in North and South America and Western Europe and Australia
- Clade C, A and AG are most common
What is a recombinant?
When clades combine and make a new virus
What is the treatment of HIV?
- HAART (immediately)
Role of gag
Codes for proteins which make up matrix, capsid and nucleoprotein structures
Role of pol
Codes for reverse transcriptase and integrase and protease enzymes
Role of env
Codes for surface and transmembrane components of viral envelope protein
