Lecture 2: Viruses II Flashcards
Viruses to know
Herpes Viruses
Papillomavirus
Smallpox
HIV
Important thing about… Herpes Viruses
viral latency
Important thing about… Papillomavirus
viruses and cancer
Important thing about… Smallpox
vaccines that work
Important thing about… HIV
Vaccines that DON’T work
Important thing about… HIV
Vaccines that DON’T work
2 ways to classify eukaryotic viruses
Baltimore Scheme (1971)
LHT (Lwoff, Horne, and Tournier) system 1962
2 ways to classify eukaryotic viruses
Baltimore Scheme (1971)
LHT (Lwoff, Horne, and Tournier) system 1962
Baltimore Scheme
group viruses by how mRNA and genome are produced
(ssRNA, etc)
the path to messenger RNA
LHT System
categories based on nucelic acid (DNA or RNA)
capsid symmetry (helicle, icosaheral, complex)
presence of envelope
diameter of capsid
number of capsomere
LHT System
categories based on nucelic acid (DNA or RNA)
capsid symmetry (helicle, icosaheral, complex)
presence of envelope
diameter of capsid
number of capsomere
Baltimore system: 7 families
ds DNA ssDNA ds RNA (+) ss RNA (-) ss RNA ssRNA-RT ds RNA-RT
ds DNA
adenoviruses
herpesviruses
poxviruses
papillomaviruses
ssDNA (sense strand)
Parvovirus
ds RNA
retrovirus
(+) ss RNA
Picconaviruses, togaviruses
(-) ss RNA
a copy will make mRNA
orthmyxoviruses, Rhabdoviruses
ss RNA-RT
Retroviruses
ds RNA-RT
Hepadnaviruses
RNA viruses…
Do NOT need to get into the nucleus of the host
Don’t need DNA polymerase from host
what is in host nucleus that virus may need
DNA polymerase
RNA polymerase
if the virus needs it, it will break in to get it
If it doesn’t encode its own DNA polymerases
what is in host nucleus that virus may need
DNA polymerase
RNA polymerase
if the virus needs it, it will break in to get it
If it doesn’t encode its own polymerases
What metabolism goes on in a virion…
NONE
nothing is going on inside the virion
they’re inert
problem with LHT
based on observation of virions…which are inert and have little to do with what the virus does in the cell
problem with LHT
based on observation of virions…which are inert and have little to do with what the virus does in the cell
review graph on 9
review graph on 9
when do you get to the acute phase?
when the innate immune system didn’t do its job right away
phenotypes of acute phase
cough
sneeze
sweat/fever
what is happening in the accute phase?
immune system being activated
which is the phase with no observable phenotype and very few virions outside cell?
ECLIPSE PHASE
eclipse phase
no symtoms and no virions seen because the virus is replicating inside the cell
eclipse phase
no symtoms and no virions seen because the virus is replicating inside the cell
review graph on 10
review graph on 10
persistent phase
spike of acute first
viremia subsides
low level of virions observable
HIV
Latent virus
acute phase happens
long period of time with no observable virions
Herpes simplex
Latent virus
acute phase happens
long period of time with no observable virions
Herpes simplex
Alpha Herpesviruses
dsDNA
enveloped
egress
Alpha Herpesviruses Simplex I
cold sores
infection of skin, and neurons
Alpha Herpesviruses Simplex II
genital herpes
other herpesviruses
chickenpox, shingles
Where/How herpes infects
epithelial and neural cells (PNS, NOT CNS)
hides in ganglia, traffics to surface, erupts when it infects epithelial cells
what causes herpes sores?
immune response to virus
stress and herpes
stress induces disease
you become immunocompromised when stressed,
when immune system comes back on after stress, it recognizes the virus and does its job
herpes simplex and immune evasion
- infects immunologically privileged cells (neurons–because we dont send the immune system to nerves much so we dont kill them)
- affects antigen presentation… reduces MHC1 on surface
- the infection can persist without virion production (virus turns off all genes when it is just sitting there…until stress happens and immune response weakens)
herpes simplex and immune evasion
- infects immunologically privileged cells (neurons–because we dont send the immune system to nerves much so we dont kill them)
- affects antigen presentation… reduces MHC1 on surface
- the infection can persist without virion production (virus turns off all genes when it is just sitting there…until stress happens and immune response weakens)
Human Papillomavirus
dsDNA
non enveloped
causes warts, cancer
HPV vaccines
Gaurdasil: cervical cancer vaccine, 11-26 year olds (all now, new, better vaccine)
HPV causing cancer
two families of it cause 70% of cervical cancers
490,000 new cases of cervical cancer a year, 270,000 deaths… but its a preventable cancer
HPV and sex
over 100 genotypes
most common STI, affects 50% of sexually active people in US
HPV infection, transmission, and function
infects EPITHELIAL cells
transmitted via contact, even shaking hands can cause warts (not cancer)
TRANSFORMING VIRUS
HPV as a TRANSFORMING VIRUS
changes the host cell
can change it to a cancer cell
types of HPV
over 150 identified
only like 15 cause cancer… all are mucousal
review slide 16 for breakdown of HPV infections
16
review slide 16 for breakdown of HPV infections
16
what is cancer
abnormal cell growth
what causes cancer
mutations
what immune response usually deals with cancer
NK cells
kill cancerous cells
Cancer and Cell cycle
when DNA damage checkpoints aren’t working right, growth can get out of control
how a healthy cell becomes cancerous
many different mutations occur over time
initially, mutations happen in checkpoints–which allows other mutations to occur
how a healthy cell becomes cancerous
many different mutations occur over time
initially, mutations happen in checkpoints–which allows other mutations to occur
late mutations (after mutation at cell cycle check point)
immune evasion
insensitivity to apoptosis (it won’t die)
acquisition of own vascular system
ability to colonize other organs
ability to survive hypoxic (low oxygen) conditions
late mutations (after mutation at cell cycle check point)
immune evasion
insensitivity to apoptosis (it won’t die)
acquisition of own vascular system
ability to colonize other organs
ability to survive hypoxic (low oxygen) conditions
Oncogenes
any genes with potential to convert normal cell to cancerous cell
Proto-oncogene
cellular gene that can promote cancer if mutated
Viral-oncogene
virally encoded oncogene
HPV has 2 of these…. these strains affect E6 and E7 in early stage—messing up checkpoints
Papillomaviruses
non enveloped dsDNA ancient family... 350 million years old infect ALL mammals, some birds, reptiles VERY HOST SPECIFIC
Papillomaviruses
non enveloped dsDNA ancient family... 350 million years old infect ALL mammals, some birds, reptiles VERY HOST SPECIFIC
How Papillomaviruses work
increase action of E6 and E7 genes… these inhibit checkpoint proteins PRB and p53
cells go through checkpoint without stopping
E=early genes, L=late genes
why does the virus want to skip the checkpoint?
virus needs replicating cells so it can replicate
needs to go through cell division so virus can get access to nucleus
what else does the virus do? (HPV)
turns telomere on
immortalization of a cell
cell then replicates uncontrollably and can live forever
what else does the virus do? (HPV)
turns telomere on
immortalization of a cell… usually only undergoes replication 180 times
cell then replicates uncontrollably and can live forever
HPV life cycle
1) virus enters through breakage of skin from sex… doesn’t infect surface cells since they aren’t replicating, has to go to cells at bottom
cells at bottom don’t produce virions, cells at top do… virions released into mucous
no immune cells in mucous, but thats where they need to be… a little immune evasion
effects of HPV genes E6 and E7 blocking checkpoint protiens
promoting faster growth
allowing more mutations indirectly
HPV-induced Cervical Cancer is a slow process
it becomes a pro-virus: integrated into chromosome
replicates on chromosome
virus makes no virions when in chromosome… the virus is not being shed BUT
E6 and E7 go through the room, shut off all the checkpoints
HPV-induced Cervical Cancer is a slow process
it becomes a pro-virus: integrated into chromosome
replicates on chromosome
virus makes no virions when in chromosome… the virus is not being shed BUT
E6 and E7 go through the room, shut off all the checkpoints
Henrietta Lacks and HeLa cells
died of cervical cancer complications in 1952
her cells were first tissue culture cells
first human cells in space
polio vaccine developed on her cells
still used in tons of laboratories today
