4. Retroviruses Flashcards
What are the 3 different types of RNA viruses? Give examples.
What are retroviruses and how do they differ?
The gene order in all retroviruses is invariant: 5’- gag-pol-env - 3’. What do the following code for:
a) gag
b) pol
c) env
- dsRNA +ve sense e.g. rotavirus
- ssRNA +ve sense e.g. polio
- ssRNA -ve sense e.g. influenza, rabies
2 identical strands of +ve sense ssRNA. Reverse transcriptase generates DNA intermediate -> integrated into host genome (provirus) -> cellular machinery produces new viral genomes. E.g. HIV. Antiretrovial therapy targets transcriptase.
a) structural proteins (matrix, capsid etc.)
b) reverse transcriptase, integrase, protease
c) surface and transmembrane components of the viral envelope protein Env
What is the function of the following:
a) reverse transcriptase
b) integrase
c) protease
What are the 2 main groups of retroviruses? Give examples of both.
What is the receptor for HTLV?
a) transcription of viral genome RNA to DNA
b) integration of dsDNA into host genome, forming provirus
c) after release of new virion, cleavage of certain proteins is needed for viral maturation and infectivity
Oncovirinae: EBV, KSHV, HPV, HBV, HCV, HTLV-1, HTLV-2, 3 and 4 (human T-cell lymphotropic virus). Cause about 12% of human cancers
Lentivirinae: HIV-1, HIV-2
Glut-1
What 3 diseases is HTLV-1 a causative agent of?
And HTLV-2?
Adult T cell leukemia (clonal aggressive malignancy of CD4+ T cells, skin involvement v common (pic)), HAM (HTLV-1 associated myelopathy)/TSP (tropical spastic paraparesis)
Sporadic cases of myelopathy resembling HAM/TSP and hairy cell leukemia. Long latency period: 20-30yrs
What is HAM/TSP?
What is hairy cell leukemia?
How is HTLV transmitted?
HTLV associated myelopathy/tropical spastic paraparesis. Chronic progressive disease of the NS -> weakness, stifness, spasms, sensory disturbance, sphincter dysfunction. Affects adults in equatorial areas.
Accumulation of malignant B cells (hairy cells). Leukemia cells collect in spleen and it swells. May be too few normal WBC b/c leukemia cells invade bone marrow. Marrow can’t produce enough normal WBC = decreased resistance to infections.
Cell-cell contact across a viral synapse. Mother to child (breast feeding), unprotected sex, contaminated blood products
What is tax?
How is HTLV and ATL (adult T cell leukemia) treated?
What is the difference between HIV-1 and HIV-2?
How can HIV be transmitted?
Trans-activator, activates cellular transcription factors which inactivate tumour supressor genes. Mutations accumulate.
HTLV: no treatment for carriers. ATL: conventional chemotherapy for lymphoid malignancies often ineffective, ongoing trials
HIV-1 causes worldwide pandemic. Chimp origin. HIV-2 mainly confined to W Africa, less virulent and not transmitted as easily. Sooty mangabey origin.
Unprotected sex, vertical (in utero, birth, breastmilk), injection drug use
What 2 things does a HIV infection require to infect target cells?
How does the viral load act in someone newly infected?
Why is it hard to develop a vaccine for HIV? What is used to treat it?
CD4+ and a chemokine receptor (CXCR4/CCR5)
Doesn’t show many symptoms at first, viral load climbs in first 3w to reach peak 3-6w after exposure. Coincides with peak decline of CD4+.
Lots of diversity of HIV among just one group of pts. Tx: HAART, decreases viral load. But can’t cure HIV. New idea = stem cell based approach to Tx, generate SC from blood, manipulate them to be resistant to HIV infection and put back in person.
What are the following opportunistic infections that could be found in someone with AIDS?
a) Kaposi-Sarkoma, human herpesvirus 8
b) CMV-retinitis, cytomegalovirus
c) Interstitial pneumonia, Pneumocystis carinii
d) Oral leukoplakia, EBV
e) Oral candidiasis, Candida albicans
What are some advantages of potentially using haematopoietic stem cells to cure HIV?
Can reconsitute and produce naive populations of immune cells for long periods. Can genetically manipulate (e.g. antigen recognition, insensitivity to infection). Derived in autologous fashion so immune tolerant.
