the last last test ever Flashcards
ebola
ebola hemorrhagic fever
ebola can actually be caused by
one of 5 closely related viruses called ebola viruses
ebola outbreaks happen frequently
in African countries are usually small
Ebola viruses’s genomes contain
just 7 genes
ebola virsues characterized as
zoonotic
how did ebola spread first through
bats, then to primates then to humans
human to human ebola is thru
body fluids»» blood, feces, vomit, tears, breastmilk
Ebolavirus spread to humans is thought to be linked to
eating bushmeat - meat from wild animals
primary virulence factor of ebolaviruses
GP
GP
glycoprotein
what are glycoproteins
membrane proteins that hold out long chains of sugars
what has glycoproteins
viruses, bacteria, human cells
recall: humans have a
glycocalyx that serves as a cellular ID tag
ebolaviruses show many normal disease symptoms like
malaise, sore throat, pain
three scariest symptoms of ebola
- severe leukopenia
- hemorrhage (extensive bleeding)
- liver failure
leukopenia
reduced white blood cell count
ebola causes disease by targeting what 4 main cell types
- dendritic cells
- macrophages
- endothelial cells in blood vessels
- hepatocytes
dendritic cells and macrophages
both are WBCs that hang neat mucosal surfaces
hepatocytes
liver cells
macrophages and dendritic cells have
protein on their membrane: DC-SIGN
DC-SIGN
dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin
what do DC-SIGNS look for
host glycoproteins… but recognize ebolavirus GPs as host GPs
As all good adhesion molecules do…. DC-SIGNS
adhere to ebola and host glycoproteins»_space;> TRAP
after ebolaviruses bind to DC-SIGN
ebola viruses are engulfed and reproduce in about 8 hours
after ebolaviruses are engulfed by the host cell and reproduce
newly assembled viruses exit hosts through budding»_space;» but eventually host lysis happens too
after ebolaviruses exit the host through budding (lysis eventually too)
infect other white blood cells
white blood cells like macrophages and dendritic cells
tend to hang out in the lymph system
interferons (ebola)
produced in response to viral infection»> kill adjacent cells
in the lymph nodes (ebola0
more WBCs»_space;> ebola causes interferons to cause leukopenia
because the lymph system connects
with the circulatory system… it also does the transport of fluids itself
because the lymph system connects with the circulatory system (and does transport of fluids itself), (ebola)
ebola is able to easily spread to other sites around the body
in response to infection (ebola), white blood cells also secrete
many proinflammatory cytokines in response
secretion of proinflammatory cytokines causes
swelling of blood vessels
so since cytokines cause the inflammation of blood vessels (ebola)
inflammation of blood vessel increase their permeability to WBCs
when The inflammation of blood vessels increases their permeability to WBCs (ebola)
allows cells w/ ebolavirus to dig deep into blood vessels
so if cells with ebolavirus are able to get deep into blood vessels
free ebola then encounters usually-isolated endothelial cells
once ebolaviruses encounter endothelial cells
causes newly-exposed endothelial cells to stop sticking to one another
how do ebolaviruses causes newly-exposed endothelial cells to stop sticking to one another.
not completely understood, but it is proposed that Ebolavirus GP binds to endothelial adhesins
when Ebolavirus GP binds to endothelial adhesins
physically stops them from sticking to one another
so since Ebolaviruses cause newly-exposed endothelial cells to stop sticking to one another
blood vessels quickly disintegrate all across the body
when ebola viruses causes blood vessels to quickly disintegrate across the body
causes widespread bleeding (hemorrhage)
hemorrhage from blood vessel disintegration in ebola
leads to DIC
DIC
disseminated intravascular coagulation—- tiny blood clots
DIC leads to
organ failure, which leads to death
ebolaviruses also sometimes enter
hepatocytes (liver cells) , typically not until later in infection
infection of ebola in hepatocytes
(how or why not sure?) leads to hepatocyte apoptosis
enough dead liver cells
LIVER FAILURE
cure for ebola
no cure for ebola virus fevers, treatment by managing symptoms
no vaccine for ebola». now there IS ???!
VSV add ebola’s GP gene to genome `
VSV
Vesicular Stomatitis Virus,
VSV is what?
Baltimore group V virus, typically infects cattle
from VSV and ebola GP gene vaccine humans
build antibodies to target ebola GP and gain (full?) immunity to ebola.
viruses that use ____ defy
use reverse transcriptase defy the central dogma of biology
central dogma of biology
DNA is read and “turned into” RNA (transcription) RNA is read and “turned into” protein (translation)
reverse transcriptase
enzyme that reverses transcription: turns RNA into DNA
after reverse transcriptase turns RNA into DNA
viruses take the DNA produced and insert it inside the host’s DNA
how do viruses take the DNA produced and insert it inside the host’s DNA
protein integrase
reverse transcriptase is
notoriously unreliable: extremely high rate of mutation
rate of mutation reverse transcriptase
appox. 1 in 2000 bases!
viruses using reverse transcriptases fall into two groups
- retroviruses
- hepadnaviruses
retroviruses
- Baltimore Group VI
- Have (+) ssRNA
most important example retroviruses
HIV
hepdnaviruses
- Baltimore Group VII
- Have dsDNA
most important example hepdnaviruses
hepatitis B
what Baltimore classification uses reverse transcriptases
group VI group VII
in the viral life cycle (RT), reverse transcription inserts
right after entry!
in the viral life cycle (RT), insertion into Host DNA
right after reverse transcription
reverse transcription the viral
viral RNA converted to VIRAL DNA
insertion into host DNA:
Viral DNA joins human chromosomes
HIV
Human Immunodeficiency Virus
HIV leading cause of death
from infectious disease (or 2nd to TB)
HIV enveloped
IS ENVELOPED
HIV falls into what
Baltimore group VI
how many genes HIV
9
how can HIV be transmitted
- only blood contact
- sexual contact
- childbirth/breastfeeding
infection of HIV most associated with
AIDS
AIDS
Acquired Immunodeficiency Syndrome
what is AIDS
condition defined by a severe deficiency of important immune cells.
T cells
type of white blood cell produced by the thymus
thymus is just
just superior to the heart
like B cells, T cells
T cells are also antigen-specific
T cells has special receptors on their membrane are caused
T cell receptors(TCRs).
T cell receptors(TCRs).
look for digested pieces of stuff that macrophages anddendritic cells have broken apart in phagocytosis
if T cells find bad stuff
trigger events
types of T cellls
- cytotoxic T cells
- helper T cells
- regulatory T celld
cytotoxic T cells
they will hunt down and kill cells that contain a certain antigen
helper T cells
producing cytokines that will attract B cells, cytotoxic T cells and macrophages and cause white blood cell hematopoiesis
regulatory T cells
they shut down other T cells at the end of an immune response
HIV virion has
glycoprotein made of two subunits
glycoprotein of HOv subunits
p120 and gp41
Gp120 binds to
CD4 receptors
CD4 receptors
glycoproteins located on the membrane of a variety of white blood cells including helper T cells, macrophages, and dendritic cells
Gp120 binding to CD4 receptors goves HIV
its primary attachment
after HIV gets primary attachment`
a second host membrane protein is required (called a co-receptor) for viral entry
main co-receptor HIV
CCR5
what does CCR5 do
looks for host chemokines but instead binds to gp120
when gp120 is bound to CR4 and CCR5
gp41 will imbed itself inside the host cell’s membrane
once gp41 imbeds itself inside the host cell’s membrane (HIV entry)
fusion between virus envelope and host membrane begins
the man who couldn’t catch HIV
Stephen Crohn , homosexual, lots of his friens died ….. BUT he never got it
Genomic analysis Stephen Crohn
32 base pair deletion mutation in both genes coding for CCR5
what was the name of Crohn’s mutation
CCR5 (draw triangle) 32
CCR5 (draw triangle) 32 altered to the point
CCR5 protein so that it did not function.
WITHOUT FUNCTIONING CCR5
HIV virus could not enter cells so people could not get infected!
HOMOZYgOTES for CCR5 (draw triangle) 32 mutation
extreme resistance to HIV infection
the the number of HIV viruses in the body multiply
as the number of viruses in the body multiplies exponentially, ONLYYY the number of CD4+ WBCs dramatically begins to drop
eventually in an HIV infection the immune system
catches up, begins defeating virus at faster rates
when the immune system catches up and begins defeating HIV virus at faster rates
he number of viruses in the body decreases sharply, but it is too late: t
when the immune system starts defeating HIV viruses, why is it too late?
HIV genome has already been inserted into the DNA of millions of white blood cells across the body
when the immune system causes the number of viruses to decrease sharply, but HIV genome has already been inserted
latency period
latency period HIV
no obvious symptoms are present, but there is a slightly decreased CD4+ WBC count and a person is still contagious
graph
memorize
recall reverse transcriptase
is very sloppy
HIV does what at high rates
mutates at alarmingly high rtes
HIV rate of mutation
as many as 10 billion unique HIV strains each day
the rapid mutation of HIv causes
makes it harder for immune system to detect
slowly, during (HIV) latency
viral levels slowly rise and CD4+WBC levels drop
A patient has aids when
levels of WBCs with CD4 drop below 200 cells/mm3
normal levels of CD4+WBC
500-1500 cells/mm3
immune systems of people with aids
so weak, they are vulreable to new infection most healthy wouldn’t get
infections of people with aids care caused by
opportunistic pathogens , sometimes FATAL :(
various causes of death in AIDS patients
rare cancers or rare infectious diseases
in many cases the infectious diseases of AIDS patients……
caused by pathogens that are present but latent in most people
all blood cels come from one cell type
hematopoietic stem cells
if more B lymphocytes are need
B lymphocytes do not divide
to get more B lymphocytes
hematopoietic stem cells divide and one daughter becomes a B lymphocyte.
HIV is what type of virus
retrovirus…causes mutation in host cell DNA
even though HIV is a retrovirus
hasn’t been shown to cause increased rates of cancer in those cells
why dosen’t HIV cause increased cancer in host cells
HIV infects mostly T cells and other white blood cells that have already finished their growth cycle»»
since HIV infects mostly T cells and other white blood cells that have already finished their growth cycle»»
hese cells don’t divide and you won’t get cancer!….. except you will…..(but not in those cells)
HIV kills
which strongly weakens the immune response
since HIV strongly weakens the immune response
weakens the immune response to other viruses that can cause cancers
examples of AIDS-defining cancers
- Human herpesvirus 8
- Huuman herpesvirus 4
Human Herpesvirus 8
usually lies latent in people,10 5 are infected
HHV8
Human Herpesvirus 8
if a person is immunocomprimised HHV8 can cause
cause Kaposi’s sarcoma to form in connective tissue.
tell-tale sign of aids
Kaposi’s sarcoma
HHV mechnaism
not a retrovirus - \\stealing host genes and turning them up or down to cause cance
human herpesvirus 4 also called
Epstein-Barr virus, is present but latent in 45-70 of people
human herpesvirus 4 can cause what lymphoma
Non-Hodgkin’s lymphoma if its levels get too high (from immunocompromisation)
Epstein-Barr virus is also
no a retrovirus,
Epstein-Barr binds to
mdm2 and stops it from unbinding p53, so p53 is inactive
cure HIV
no cure no vaccine, but treatments
one of main treatments HIV
ART
ART
Antiretrovial therapy
Antiretrovial therapy
is a series of many different medications that aim to stop HIV activity.
some targets of ART to stop HIV are
- CCR5 protein blockers
- integrase inhibitors
- reverse transcriptase inhibitors
- protease inhibitors
protease inhibitors
may stop budding
ART treatments work to
extend the latent period of HIV, slow development of AIDS
all viruses are
obligate intracellular parasites
what does it mean to be an obligate intracellular parasite
cannot make ATP or proteins without using hosts’s parts
a full virus unit
virion
three parts of a virus
capsid
genome
accessories
capsid
protein coat around the outside of a virion
genome
the DNA or RNA a virus contains
accessories
envolelope (?), matrix, spikes and other stuff
viruses range in size from
10-400 nm
bacteria range in size
500-5000 nm
questions to ask to classify viruses by examining the genetic material they contain
- is it DNA or RNA
- single-stranded or double-stranded
- (+) sense or (-) sense
if genetic material is sense or positive sense
means that an mRNA sequence with the same sequence will code for a protein
grouping system based on examining the genetic material
Baltimore Classification system
2nd way to classify viruses
enveloped or naked
what is the viral envelope
phospholipid bilayer that surrounds the capsid
what does the viral capsid do when it exits the host
steal the membrane of the host cell to form the viral envelope
before the viral capsid exists host cells
they force the host to produce their own viral membrane proteins and put them in that membrane (that they will steal for their envelope)
the result of the viral envelope pathway
viral envelopes with host phospholipids but THE its VIRAL PROTEINS are made by the host’s ribosomes
soooooo viral capsid to enveloped virion
viral capsid takes some of host cell membrane that produced viral glycoproteins
pros for a virus containing a viral envelope
- does not need to kill host cells to spread
- cannot be fought off only with antibodies (harder to vaccinate)
cons for a virus containing a viral envelope
- sensitive
- requires a more complex genome to make envelope proteins
what are viral envelopes sensitive to
pH, temperature, drying out, heat
since viral envelopes are sensitive to pH, temperature, drying out, heat
cannot survive in GI tract or outside of body, sensitive to detergents
the life cycle of a virus
- attachment
- entry
- replication and protein synthesis
- assembly
- release
ATTACHMENT
virus recognizes and attaches to victim cell
ENTRY
virus (or virus parts) enters victim cell
REPLICATION AND PROTEIN SYNTHESIS
victim cell hijacked, makes viral DNA/RNA and proteins
ASSEMBLY
viral parts come together and make new viruses
RELEASE
new viruses exit the victim cell
Step 1: attachment is mediated by
envelope or capsid proteins called VAPs
VAPs
viral attachment proteins
there is usually what that a virus specifically targets
one specific surface protein or pattern that a virus
since there is usually one specific surface protein or pattern that a virus specifically targets
many viruses target just one specific tissue
step 1: attachment can be blocked by
antibodies…… so the immune system often tries to inhibit attachment
in step 2: entry, the
process is different depending on if the virus is enveloped or naked
entry naked
virus is taken through endocytosis
entry enveloped
viral phospholipid bilayer fuses with host cell or virus is taken through endocytosis
in step 3: replication and protein synthesis
-DNA is “turned into” RNA in the nucleus (transcription)-RNA is “turned into” protein in a ribosome (translation
translation occurs
outside the nuckeus
depending on a viruses genetic materia, DNA/RNA replication can happen in many ways: if the virus has DNA
- the DNA must enter the nucleus to be copied into RNA before making proteins outside the nucleus (usually)
dna/Rna replication: if the virus has RNA
-If the virus has RNA, it may or may not need to be transcribed to a positive form, but does not need to enter the nucleus (usually)
unlike bacteria an eukaryotic cells, virsues
don’t replicate through division, instead new viruses are asembled
where are DNA viruses assembled
in the nucleus
where are RNA viruses assembled
in the cytoplasm
assembly enveloped viruses
produce some of their envelope proteins in the host’s membrane, which they plan to pull off with it later.
how do the parts of virus assembly know where to go
slight magnetic forces
step 5; release
virus levea host cell, different depending if its enveloped or naked
naked release
lysis: virus is copied many, many times inside, then invokes host cell “popping”.
enveloped virus release is…..
lysis or budding, generally the host remains intact but part of the membrane is stolen
enveloped virus release
virus is copied inside, assembled, and released by “budding” off of the original host cell.
viruses can cause harm by inhibiting
host cellular DNA, RNA, or protein synthesis
viruses can cause harm by damaging
endosomes or lysosomes by releasing cutting enzymes
viruses can cause harm by adding
viral proteins to host cell membranes (autoimmunity)
viruses can cause harm because some
some viral proteins are toxic to host cells
a large buildup of viruses
inclusion bodies
viruses can cause harm because inclusion bodies
physically block cellular processes from haooenning
which damage is unique to retrovirus
chromosome damage , cancer causing mutation such as proto-oncogenes areunique to retrovirus
retrovirus
viruses that add their DNA to ours
types of viral infection
acute, chronic, latent, viruses can show different diseases at different stages
acute infection
you get the virus, you get sick a few days later, you die or beat the infection
chronic infection
you get sick, you may or may not show symptoms, you have the virus for a long time or forever
latent infection
you get the virus, you may or may not show symptoms, then there is a long delay before symptoms show again
how do we fight off viral infections
antibodies, type 1 MHC, interferons
to fight off viral infection, the antibodies we make
block most VAPs, and are most effective on naked viruses
MHC
membrane protein on all human cells
MHC is a form of
form of self-ID : Proteins destroyed by proteasome are dangled from the membrane and “sniffed” by WBCs
if proteins dangled from MHC are non-self
the cell is killed by WBCs
IFNs
interferons
interferons
a type of cytokine that cause all adjacent cells to turn on many anti virus genes
interferons signals uninfected
neighboring uninfected cells to destroy RNA and reduce protein synthesis
interferons signals infected
neighboring infected cells to undergo apoptosis
interferons activate
activate immune cells
influenza and ebola are caused by
Baltimore group V viruses
what type of RNA causes influenze and ebola
ssRNA
what else are caused by group V viruses
Measles, mumps, rubella, rare and lesser-known disease
influenza and ebola are env
ENVELOPED
influenza and ebola survival
do not survive long outside of a host and are spread only through fluids
genetic material of group V viruses
(-) ssRNA
ssRNA must be
turned into an antigenome of (+) mRNA to make proteins , happens in cytoplasm of host
after (-) ssRNA is turned into (+) mRNA
copied into more (-) RNA to make more viruses
3 forms of influenza
influenza A
influenza B
influenza C
influenza A
the scariest and most contagious form… since affects many species , mutates fastest
what species do influenza infect
humans, birds, pigs, seals , horses
influenza is further broken into
classes based on the presence of H and N antigens
influenza B
only transmitted by humans (and seals?)
influenza B mutations
2-3x slower than influenza A
influenza C
rarely causes human disease and is not considered a threat
influenza A strains have how many genes
just 11
two of the influenza A genes code for
important envelope proteins
one of the important influenza A genes
HA
HA
codes for hemagglutinin
how any HA pattenrs
18, (H1-H18)
Hemagglutinin is responsible for
attaching influenza virus to sialic acids
sialic acids
sugars found outside the membrane of many human cells
hemagglutinin promotes
viral attachment
almost all human flu strains have only the
H1, H2, or H3 antigen
H1, H2, H3 antigens attach to
2,3-linked sialic acid
2,3-linked sialic acid is
found outside the membrane of upper respiratory cells
thus……… because of the H1, H2, H3 antigen
the flu attaches to, and invades and infect cells in the upper respiratory tract
the H5 is
found in avian flu viruses
H5 antigen attaches to
2,6-linked sialic acid
2,6-linked sialic acid is found
outside the membrane of lower respiratory cells
deep tract influenza from H5
BAD…… bird flu… 50 PERCENT MORTALITY
what is the other influenza A gene that codes for an important envelope protein
NA
NA codes for
neuraminidase
how many known NA patterns
11 (N1-N11)
neuraminidase is responsible for
cleaving sialic acids off cell membranes, allowing the flu virus to detach
only which NA patterns are seen in the human flu
N1 and N2 , and rarely (N3, N7, N8)
before the flu virus detaches
it attaches initially w/ hemagglutinins on sialic acid
the flu exhibits both
genetic shift and genetic drift
genetic shift
combination of different flu types in one cell
in genetic shift the genetic material is
swapped around and a new superflu develops
what was an example of genetic shifting 2009
H1N1 swine flu outbreak of 2009
example of genetic shift
Avian H5N2 and swine H2N1 create dangerous H5N1
influenza pandemic of the 20th century
spanish flu, asian, hong kong…. all A
genetic drift
the slow mutation of one flu type….. usually just one amino acid at a time.
antibodies are super
specific
since human antibodies are extremely specific, so one small mutationn
can make antibodies ineffective
because of genetic drift you can catch the flu
many different times
how many total amino acids in HA
527
example of genetic drift
H1N1 mutates to have slightly different H structure many antibodies no longer recognize
because genetic drift you can get sick
You can get sick again - just maybe not as sick as last time.
In genetic drift, some antibodies
still recognize the antigen, but others do not (you have a “partial” immunity but not a full one)
why did the swine flu kill so many young adults
many older people had antibodies that recognized H1 or N1 components from much earlier infection…. young didn’t
exciting news for H antigens
antibody shown to recognize all variations of all H antigens in influenza A!
yearly flu vaccines
guess he most likely flu infection to happen each year
to guess the flu
ook at data from previous years to choose the H and N subtypes most likely to be found the next year
flu vaccines are the form of
attenuated or killed version of the vaccine
flu vaccines predict the genetic -______
genetic drift of the flu virus
flu vaccines are typically
trivalent: they include three separate guesses
two guess for flu vaccine
influenza A (H1M1 and one for H3N2)
one guess for flu vaccine
influenza B
they are NOT guessing (flu)
whether the main strain is carrying H1, H3……. but which version of H1 or H3 will be carried
what is often given to flu patients
antibiotics,,,, even though the kill bacteria
most flu symptoms
caused by own immune system
flu ymptoms caused by immune system
fever, cough, mucus, inflammation
the flu also invades and kills
ciliated, mucus-secreting cells
when the flu also invades and kills ciliated, mucus-secreting cells.
reduces the defense of the airway
becuse the flu reduces the defense of the airway it is associated w/ a
secondary respiratory infection
the ______ protein in influenza has been shown to stop______
NS1 protein……. shown to stop host cell mRNAs from being completed
NS1 protein……. shown to stop host cell mRNAs from being completed …….. causes
slowing production of host porteins…… NOTEWORTHY»»> interferons
the current version of the H5N1 bird flu has
single nucleotide mutation that makes NS1 protein far more virulent
we’re lucky about H5N1 because
it’s hard to invade humans…. for now
major cytokine in the body is
TNF-a
TNF-a
tumor necrosis factor alpha
tumor necrosis factor alpha has many functions is effective @
stopping influenza infection.
release of TNF-α has been shown to be
“dose-dependent”…. more flu = more TNF-α.
dose-dependant is normally fine…… but like most cytokines TNF-a causes
inflammation, swelling, and white blood cell migration.
too much inflammation, swelling, and white blood cell migration @ site of infection
ARDS
ARDS
acute respiratory distress syndrome
acute respiratory distress syndrome
lungs swelling shut and filling with fluid
ARDS is common in flu types that
target lower respiratory tracts
ex of flu causing ARDS because it target lower respiratory tracts
like the 1918 H1N1 Spanish flu outbreak that killed 30-40 million people.
