Retroviruses Flashcards
what type of genome does the Rous sarcoma has?
RNA genome
what is Crick’ “Central Dogma”?
“once information has got into a protein it can’t get out again”
what is the Rous sarcoma virus replication dependent on?
DNA
what effects does Actinomycin D has on RNA synthesis?
Actinomycin D inhibits transcription and hence RNA synthesis
what inhibits virus growth?
Actinomycin D
what route did the effects of actinomycin D in sarcoma suggested?
RNA -> DNA -> RNA -> Protein
what is the provirus hypothesis?
the provirus of Rous sarcoma is a region of DNA homologous with viral RNA stably integrated into the molecule of cellular DNA in the nucleus
what is used to fight against HIV?
reverse transcriptase inhibitors
what is the viral RNA dependent on?
DNA polymerase
what does the reverse transcriptase do?
turns RNA back to DNA
what are the subfamilies in the family retroviridae?
orthoretrovirinae and spumaretrovirinae
how are retroviruses transmitted?
transmission typically via close contact (oronasal, sexual, blood-borne)
what protects the retrovirus?
a lipid envelope
why does the retrovirus have an envelope?
because it is susceptible to desiccation and detergents (that’s why the envelope has lipids)
what are the key features of retroviruses?
- two copies of RNA genome in each viral particle
- reverse transcribe RNA to DNA
- DNA “provirus” integrates into cellular DNA
- establish persistent infections
what does the “gag” gene encode in the retrovirus genome?
core structural proteins
what does the “pol” gene encode in the retrovirus genome?
- enzymes for replication
- reverse transcriptase
- integrase
- protease
what does the “env” gene encode in the retrovirus genome?
envelope glycoproteins
how do retroviruses infect cells?
by binding to a cell surface molecule called the receptor
- it binds to a nuclear pore and once it binds it starts replicating
what is necessary for a productive viral life cycle?
integration
where do simple retroviruses (e.g. FeLV) integrate?
in dividing cells
where can lentiviruses (e.g. HIV) integrate?
in non-dividing cells
what is integration?
the retroviral genome integrates into the cellular DNA and becomes part of the host
how much of the human genome is derived from ancestral retrovirus infections?
8.3%
what does integration do?
maximises the chance of viral transmission
which retroviruses integrate?
all
how does the retroviral assembly work?
- RNA makes a poliprotein (single long protein?
- sticks under membrane
- bends the membrane
- becomes more circular
- protein inserted in this new molecule
- has to be cut off from membrane
- forms an immature molecule
- then matures
where do some of the retroviruses assemble?
at the pericentriolar region of the nucleus, the fully assembled particles then migrates to the cell surface
is there any vaccine against retroviruses that is effective?
only the feline leukaemia (FeLV) vaccine works
what does the FeLV cause?
immunosuppression, tumours, anaemia
which are the subgroups of FeLV?
three subgroups: A, B, C, classified according to the viral envelope glycoprotein
from where has the FeLV-A subgroups been isolated?
from all infected cats
where are the FeLV-B and C subgroups generated?
within the host
how viral is FeLV?
cats may clear the virus or become persistently infected
what do retroviruses establish?
persistent infections
what does the bovine leukaemia virus cause?
zoonotic bovine leukosis
what does the bovine leukaemia virus infect?
B lymphocytes
are there free virus in the blood in bovine leukosis?
no
what doe persistently infected cattle produce?
antibodies
what does viral tax protein trans activates?
cellular genes
how is bovine leukaemia virus transmitted?
via infected cells e.g. milk, blood
how can bovine leukaemia virus be transmitted?
vertically or horizontally
which are the oncogenic retroviruses?
- alpha avian leukosis viruses (ALV)
- beta Jaagsiekte sheep retrovirus (JSRV)
- gamma feline leukaemia virus (FeLV)
- delta bovine leukaemia virus (BLV)
what are the mechanisms of retroviral oncogenesis?
- oncogene capture and transduction
- insertional activation
- insertion leading to truncation
- insertion leading to gene inactivation
- other mechanisms
how can retroviral proteins lead to tumour formation?
they can deregulate normal cellular metabolism and lead to tumour formation
what are the effects of an infection with oncogenic virus in the cell?
- lossof contact inhibition
- increased saturation density
- increased growth rate
- anchorage-independent growth
- tumorigenic in appropriate hosts
what causes OPA?
a retrovirus called JSRV
where does JSRV replicate?
only in type II pneumocytes and club cells
what are club cells?
bronchiolar exocrine cells
what does replication lead to?
to transformation of every cell
what does the viral Env switches on?
signals for cell division and activates cell signalling pathways
what is the incubation period of Maedi-Visna Virus (MVV)?
approx. 2 years
what does MVV cause?
ovine progressive pneumonia
how is equine infectious anaemia virus (swamp fever) transmitted?
by bitting insects (horseflies)
what is associated with the emergence of viral emergents?
episodic pyrexia/illness
what are the treatments for swamp fever?
there are no treatment options
what is swamp fever related to?
immune complex formation, complement activation
what are the immunodeficiency-causing lentiviruses?
- feline immunodeficiency virus
- human immunodeficiency virus
- simian immunodeficiency virus
how many people are currently infected by HIV?
35 million people
how many deaths in sub-Saharan Africa are caused by AIDS?
76%
where do the endogenous retroviruses (ERVs) genome persists?
in host DNA
what does the integration of the retrovirus into the germ cellular DNA cause?
vertical transmission of viral DNA to offspring
what are ERVs?
transposable (mobile) genetic elements
are ERVs defective?
most of them, but not all
what do ERV-derived genes may provide to the host?
useful or essential functions to the host e.g. syncytin in placental morphogenesis
what is the fusion of the trophoblast cell layer into the continuous multinucleate syncytiotrophoblast associated with?
implantation of the embryo
what mediates the trophoblast cell fusion?
the expression of the HERV-W Env (envelope)
for what have retroviral vectors been developed?
gene therapy
what may the integration of DNA provirus lead to?
development of cancer
what is the integration of DNA provirus used for?
exploited for gene therapy
