Term
| Viruses are unique in at least four ways: |
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Definition
genetic material is DNA or RNA; doesn’t require DNA and RNA both
protein synthesis machinery is dependent on host ribosomes
Reproduction is by assembly of parts, not splitting
Not susceptible to antibiotics |
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Term
1) Viruses and chlamydia (EB/RB) bacteria have this feature in common:
2) Viruses, chlamydia, and ricketsia, have this fearture in common: |
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Definition
The have no energy synthesis capability
They all grow intracellularly |
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Term
_________ RNA is the (protein) ncoding like the mRNA strand
________ is like the template strand |
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Definition
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Term
| what is the difference between diploid and segmented virus genome |
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Definition
diploid--the segments are copies of each other
segmented -- have different stuff on each segment |
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Term
| capsid (made of capsomers) are resistant to: |
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Definition
Resistant to some detergents
Resistant to some proteases
Resistant to nucleases
Adic places, like GI tract
Resistant to drying upon defecation |
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Term
Proteins are made in ______________ for all viruses
RNA viruses replicate in the ________________
DNA viruses replicate in the _________________ |
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Definition
(ribosomes/cytoplasm)
(cytoplasm, except flu and retro)
(nucleus, except pox and hep B) |
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Term
____________strand RNA must bring its own pre-formed replicase enzyme to replicate RNA
____________ RNA has the replicase enzyme in its genetic code and makes it right away using the host ribosome |
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Definition
negative must bring it to make a positive strand intermediate that can be used by the host ribosome to make proteins and be copied to make many more negative strands...
positive strand makes the replicase using the host ribosome (makes a negative strand intermediate that is used to make many more copies of the positive strand) |
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Term
Intermediate Early proteins
Early proteins
Late proteins |
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Definition
IE are regulatory proteins to ramp things up
E are for replication
L are for structure
once DNA makes copies of itself -- EARLY phase is over -- LATE phase starts |
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Term
| difference between non-permissive cells and resistant cells |
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Definition
non-permissive let virus in but don't allow it to replicate
resistant don't allow it in (no receptor protein) |
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Term
lytic
abortive
persistent
transformation
apoptosis induced by _______ or ________ |
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Definition
cell death; virus spread
non-permissive cell; no spread
no cell death; virus spread (chronic),
no replication (latent), latent and lytic peroids (recurrent)
virus causes cancer by defeating apoptosis program OR killing cell and having tissue around it multiply--increasing chances for cancer mutation
interferon or IE regulation
interferon (induces MHC presentation--more recognition by immune system, blocks translation of virus, induces cell death, etc...) or IE proteins change regulation cell -- cell recognizes this and programmed cell death occurs (viruses can have programs that stop the apoptosis program) |
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Term
| primary infection (replication) |
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Definition
local to entry site (lungs usually) then
primary viremia
secondary infection tissue (replication)
secondary viremia
Systemic infection and Disease symptoms in Target Tissue (replication) |
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Term
T/F
antibodies can cross the Blood Brain Barrier easily and effectively |
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Definition
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Term
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Definition
acute infection (amount of virus goes up, disease episode happens, amount of virus goes down)
Acute infection with rate late sporadic disease episode after levels go down
Chronic infection (amount of virus goes up, disease episode happens, amount of virus stays up)
chronic infection with late onset of disease
slow infection - amount of virus slowly rises with late disease episode |
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Term
| fulfilling koch's postulates |
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Definition
must be found in diseased
must be isolated and grown in pure culture from diseased
must initiate the disease in another artificially infected
must be able to re-isolate original virus from the artificially infected |
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Term
Picornaviruses
Picornaviruses are classic ___________genomes
Protein stuck on end of Viral RNA is named ____________ and it is a primer for _________________
The function of the Cleft in the Pentameric Protomer with its four structural polypeptides (cleft=Canyon) is to ______________________ and _____________________
The cell receptor for Rhinovirus is _____________________
The cell receptor for Poliovirus is _______________________
Picornaviruses enter cells by __________________________
Picornaviruses replicate completely in ___________________
Picornaviruses kill the ______________________
When they __________________ their genome, they make a ___________________. This protein contains within its sequence: all of the other proteins for replication and processing of the genome; and a _________________ that breaks down the first protein into four structural proteins (VP1,2,3,4) that make the ______________________. |
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Definition
RNA, small, non-enveloped (ether resistant), icosahedral
(toga and flavi are RNA, small, enveloped, icosahedral)
rhino, polio, hep A
SS (+) RNA
VPg (on 5’ end) for RNA polymerase
The canyon houses the Viral Attachment Protein which binds the cell receptor, while the canyon also limits the accessibility of the neutralizing antibodies.
ICAM-1
CD155
receptor-mediated endocytosis
the cytoplasm
cytoplasm
Translate
Single PolyProtein
Viral protease
protomer |
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Term
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Definition
Picornavirus family
155 serotypes (antibody for one cold only covers one type -- imumunity is long-lived but not cross-reacting)
local disease to 32-35 C / ciliated columnar epithelium of Upper RT (no viremia/systemic stuff)
receptor on cells for the VAP (picorna canyon) is the ICAM-1
ammount of virus is directly related to amount of shedding
most infectious virus
-10% of pediatric visits under 2 yrs. old, 30% of respitory infections |
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Term
| Rupintrivir is a _______________ |
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Definition
| Human Rhinovirus Protease inhibitor |
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Term
| enteroviruses (poliovirus) |
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Definition
Picornavirus
-Enterovirus
--Echovirus, Coxsackie, Poliovirus
Echovirus and Coxsackie commonly infect Respitory Tract and Skin among other things;
Poliovirus infects REspitory Tract, Skin(rash), Brain, and Meninges
Polio
Oral-Fecal Encounter (entero)
Primary replication in tonsils/GI lymph
(at 2-4 days fever, GI symptoms)
Secondary replication in organs
Target Tissue/systemic invasion of the CNS/nerves (at 4-35 days paralysis/neural fatigue--depends on where the virus is replicating and killing neurons*)
endemic--maternal antibody protection (infants)
epidemic--New York 20th century sanitation lead to later encounters in life (toddlers)--more severe |
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Term
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Definition
RNA, small, enveloped (sensitive to ether)
Arbovirus (misquito vector)
Also called Alphavirus
Single stranded RNA + sense (starts translation with host ribosome)
5' cap is Non-structural stuff (codes for helicase, *replicase, etc...)
---made in ''early phase''
3' structural proteins on the 3' subgenomic part; encoded structural proteins (E1,2,3 (envelope, etc...))
---made in ''late phase'' i.e. made off of the intermediate (replicated-in-early-phase) negative strand in ''late phase''
uses plasma membrane to bud (enveloped)
primary viremia (from primary replication) -- causes flu-like symptoms -- antibodies made
secondary viremia (from secondary replication) -- if it it past antibodies
can cause ENCAPHALITIS (Target tissue/systemic replication)
Alphavirus:
causes viral meningitis (acute headache),
viral encephalitis (like meningitis, more brain involvement - confusion, seizures)
EEEV (eastern US/canada), WEEV (western), and VEEV (venezuelan, southern) (encephalitis virus)
bird, misquito, human
recent outbreak - E protein (structural envelope protein) mutant in misquito vector caused Chikungunya (arthritis) in east africa, italy, india |
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Term
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Definition
flavi
RNA, small, enveloped (sensitive to ether), icosahedral (toga and flavi are RNA small enveloped icosahedrals; rhino, polio (entero) RNA small non-enveloped icosahedral)
+ SS RNA
5' 3' orientation is opposite to Toga
Flavi 5' is Structural
Flavi 3' is Non-structural
primary viremia (after primary replication/misquito bite) causes flu-like symptoms
secondary viremia (after secondary replication in phage/liver/spleen)
causes systemic/target (replication)--
Encephalitis (CNS), Yellow Fever (liver), Dengue
Encephalitis -- West Nile, Saint Louis and Japanese (Encephalitis)
West Nile
- bird host, misquito vector, human end
- N america in 1999, blood now checked
- fever/fatigue, sometimes encephalitis, death occasionally (1/1000ish)
Saint Louis Encephalitis
- bird host, misquito vector, human end
Japanese Encephalitis
- asia, mild,
Yellow Fever Epidemics
- Liver
- many epidemics
- jungle animal, misquito, urban human
Dengue
- common in world
- jungle, misquito, urban human
- fever
- Dengue Hemorrhagic Fever - extreme vascular permeability
- Dengue Shock Syndrome
- early infection Fc receptors actually enhance second infection
Avoid misquitos
Look for Virus-specific antibody |
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Term
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Definition
SV40: a virus in family polyoma (dna, small, non-envelope, icosahedral)
prototype of polyomaviridae; has helped people study viruses,
potential link to cancer
T protein
polyoma dna - has an EARLY Large T protein involved in Transcription of mRNA and cell/cancer transformation
Small T protein involved in DNA replication
VAP
LATE phase structural proteins VP1,2,3 -- Major capsid proteins (VP1 is the VAP) |
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Term
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Definition
a Polyoma (dna, small, non-envelope, icosahedral)
respitory tract infection (primary replication)
primary viremia
secondary replication (kidney)
--immunocompetent -- latent in kidney
--immunodeficient (AIDS) -- reactivates
Target tissue replication (urinary tract, viruria, hemorrhage cyst) |
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Term
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Definition
a Polyoma (dna, small, non-envelope, icosahedral)
respitory tract infection (primary replication)
primary viremia
secondary replication (kidney)
--immunocompetent -- latent in kidney
--immunodeficient (AIDS) -- reactivates
JC viremia
Target tissue replication (CNS, PML) |
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Term
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Definition
Merkel Cell Polyoma Virus
Viral genome was detected in eight of 10 MCC tumorsb (potential link between MCPyV(virus) and MCCarcinoma)
Merkel Cell Carcinoma (redish zit-like)
aggressive skin cancer
sun-exposed extremities, head, neck |
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Term
| HPV i.e. human papilloma virus |
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Definition
like polyoma -- it has dna, small, non-enveloped, icosahedral)
infect high variety of higher vertebrates, but NO MOUSE MODELS!
circular double strand
Some open reading frames:
E1 - initiation of viral DNA replication
E6 degrade p53 function (thereby promote tumors)
E7 bind Rb (thereby promote tumors)
L1 -- capsid protein (doesn't have an envelope, so capsid has the VAP probably)
skin is constantly having abrasions where virus can get through and infect basal cells
as cells move up from basal stages and differentiate,
the virus uses this process to turn on and off its genes to
put itself together and make virus
it doesn’t escape from the cells, it gets ‘’sluffed off’’ with the cells
Can re-infect self
can remain infectious in the
environment |
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Term
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Definition
skin warts
common-rough
flat
plantar/palmar |
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Term
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Definition
anogenital warts
external genitalia
Between 1966 and 1981---170,000 to almost 1 million physician visits
they are self-limiting |
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Term
HPV 16, 18
(and....31, 33, 39, 45, 51, 52, and 58) |
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Definition
most common types of HPV associated with CANCER
HPV16 is the most common type associated with anal cancer
HPV 16 (50% cervical cancers) HPV 18 (20% cervical cancers)
likelihood of regression is inversely related to the degree
of dysplasia
Severity of lesion is shown by how much cells (cornae layers that get sluffed off) look like the basal layer cells
virus seems to be necessary for cervical cancer – but it deosn’t seem to be sufficient
E6
- HPV E6AP protein will bind p53
- cycle constantly turned on.... or cell apoptosis response
E7
direct cancer causing...P21, p27 are inhibitors of the cell cycle ----E7 binds to these
indirect
E7 protein binds hypophosphorylated pRB and pulls it away from E2F, allowing E2F to move the cell cycle into S phase (replication) |
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Term
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Definition
orthomyxo
--influenza A (flu)
RNA, large, Enveloped, helical
- ss segmented, negative RNA (uses Nucleus like retroviruses *this is an exception to the RNA-stays-in-Cytoplasm rule)
(8 segments, 10 products)
NP nucleoprotein to make the helical shell
NS1 the one Non-structural protein
HA Hemagglutinin, binds virion to host (via sialic acid) for ENTRY;
its cleavage to HA1/HA2 by the cellular(host) protease is required for MATURATION and eventual fusion
Tryptase Clara Enzyme that cleaves HA to HA1/HA2 is only in the Respitory tract---limits virus to respitory tract
M2 ion channel; H+ comes into virion, lowers pH---HA conformational change---allows for FUSION
(Amantadine drug blocks M2 channel -- blocks FUSION)
RNP's (ribonucleoproteins) are released and taken to NUCLEUS*
CAP snatching in nucleus -- RNA negative strand with its polymerase cleaves CELLULAR mRNA cap and takes it for a primer for its positive VIRAL RNA synthesis
NA neuraminidase; cleaves sialic acid---allowing virion to un-attach from cell and move on to become functional again; (NA is the target for Tamiflu)
abrupt fever, chills, headache
systemic (respitory infection); interferon (cytokines) causes systemic muscle pain/weakness
Combined Bacterial and Viral Pneumonia
Bacteria provides protease for HA cleavage |
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Term
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Definition
pandemic
for example in H1N1, the "H" changes
influenza is segmented -- if two viruses infect and you have reassortment of segments... HA molecule changes and avoids Antibodies
classic example: avian and human strain for example reassort in pig, infect humans again
1918 was rare pandemic, jumped from Avian to Human; killed 80% of army
2004 H5N1 Avian flu; had to kill a lot of chicken and ducks
- if ever jumps to humans, could be bad like 1918 or worse
2009 Swine Flu
- triple reassortment with two swine types (complex)
- H1 subtype was similar to seasonal H1 -- it is the seasonal flu now
- |
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Term
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Definition
epidemics
slow changes by point mutations
annual changes in vaccine |
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Term
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Definition
DNA, large, envelope, icosahedral
10-12 glycoproteins (the envelope necessary for attachment)
big DNA - encodes IE, E and L phases |
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Term
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Definition
herpes simplex virus type 1
usually spread by ORAL contact
cell-mediated response controls infection
latent in Trigeminal Nerve Ganglia (isn't producing virus, on Latency Associated Transcripts LAT's)
often asymptomatic, but recurrence by stress, fever, immunosuppression, light, etc...
Herpes Keratitis(keratoconjucntivitis), blindness, requires accurate diagnosis
skin herpes (wrestlers)
Herpes Encephalitis (mortality; rare, but must be detected early) |
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Term
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Definition
most common cause of Genital herpes infection
latent in sacral ganglia
asymptomatic, spread by sexual contact
antigenically similar to HSV-1
PRodrom Phase -- individual feels it coming back -- best if treated during this phase
Neonatal Herpes (5,000 deliveries per year); contact with herpes lesions in birth canal (60% die)
evil |
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Term
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Definition
Similar to HSV (latent in neurons, Cell-mediated immune response is Important, blisters; but different that it won't grow on anything--it is hard to culture)
Respitory spread/local infection
viremia
spleen/liver (secondary replication)
viremia
chicken pox (varicella) primary Target infection
latent in Dorsal Root ganglion
Age,stress,Depletion of Cellular Immunity
Shingles (zoster) recurrent infection |
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Term
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Definition
Targets B-cells (to replicate in, be latent in, to cause B cell immortality)
Burkitt Lymphoma Tumor--Epstein Barr Virus: Burkitt in Africa sends to Epstein/Barr in England, they find Epstein Barr Virus
implications---EBV is associated with Burkitts Lymphoma (in Africa/Malaria immunosupression), and Nasopharyngeal Carcinoma (in China)
--- Translocation in B-cell
EBV was then associated with Infectious (kissing) Mononucleosis --- If not exposed as baby you get it when you're older
- confirm mono by Antibody tests (heterophile antibody -- antibody attracted to sheep/horse/bovine antigen) |
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Term
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Definition
Human Cytomegalovirus
DNA, LARGER GENOME than other herpes, enveloped, icosa
latent in bone marrow
this is the virus that mother contract a primary infection and it CAN CROSS THE PLACENTA** in utero (Most prevalent congenital disease--retardation, etc...--caused by a virus)
may be cause of secondary mono (heterophile negative mono, i.e. mono that doesn't show EBV as the cause)
problem for the immunocompromised - pneumonia, latent in a kidney transplant |
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Term
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Definition
Human Herpes Virus 6,7
salivary glands, day-cares
100% adults are seropositive |
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Term
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Definition
Human Herpes Virus 8
Found in Kaposi Sarcoma lesions--another viral cause of cancer
red botches on skin, AIDS patients |
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Term
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Definition
Monkey Herpes B Virus
latent infection in monkeys
if human is bitten by monkey
respitory transmission
70% mortality |
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Term
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Definition
e.g. HIV
KEY features
Encode Reverse TRanscriptase (RNA converts to ds DNA intermediate)
jump species
1931 nonsterile vaccines, bushmeat hunting, labor camps in French Eq Africa
Exposure/initial infection
transmission by blood or sex
virus adaptation or mutation increases its survival
ubiquitous - found in a lot of animals, enogenous retroviruses in germ line cells, integrate permanent copy into genome
3 kinds: onco, lenti, spuma
oncoviruses -- transform cells -- e.g. HTLV (delta-retro)
lenti virus -- slow developing chronic, e.g. HIV
- SIV monkey virus similar to HIV
Spuma viruses not known to be associated with disease eg HFV
Receptor ENTRY
- ***people with CCR5 mutation are resistant to infection*** (need CD4 and CCR5 or CXCR4), and they don't seroconvert (they don't make antibodies)
Fusion
mediated by Env transmembrane protein (Env TM)
***there are fusion inhibitors***
RNA copy gets dumped out
- RNA: + ss RNA (two copies as dimer)
- order is Gag-Pol-Env-U3
tRNA: primer for reverse transcriptase
***there are Reverse Transcriptase Inhibitors***
U3: Promoter on 3' end, gets put into proper 5' place upon reverse transcription
DNA polymerase: makes the second strand of DNA
RNase H: removes RNA as DNA is being made; Reverse transcription happens before going to nucleus
--IT IS ERROR PRONE -- can make resistant Mutants easily
***so we must use 3 HIV drugs instead of 1
Goes to nucleus
IN: Integrase
***there are integration inhibitors***
--therapeautic implications of integration
- retroviruses containing a code for an enzyme deficient; it solved the deficiency, but caused cancer (turned on/off bad genes downstream, e.g. too much Myc made--cancer)
HIV's complex genome: extra protein factors to increase its own transcription in cell, and fight cell's transcription
RNA comes out of nucleus, makes GAG
GAG: Group Associated Antigen; thing in the matrix that gets screened for; thing that needs to be cleaved for maturation
PRO: protease cleaves GAG for maturation effect
*** there are PROTEASE or maturation inhibitors***
pol: reverse transcriptase code to start cycle all over again in next cell
ENV: envelope glycoproteins SU spikes TM anchor
Retroviruses in Nature
- Syncytin, important for Syncitioblast fusion along endometrium, same as the HERV-W envelope fusion gene
Amylase in saliva by retro-insertion of GALV upstream of amylase gene |
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Term
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Definition
flavi family (RNA, small, envelope, Icosahedral, 5' structural proteins, 3' Non-structural)
ss + RNA
5' NTR (non-translated region=helps target to ribosome for translation)
Encodes polyprotein
--NS2/3 AUTO-protease splits Structural from Non-structural, which activates the Ser protease cofactor which splits up the non-structural even more ***these proteins are potential sites for drugs***
makes a web
Replication of the new + strand and assembly (only in cytoplasm)
--HCV polymerase is error prone
---virus goes in one way and comes out another
---hard to develop vaccine against
2005 - Producing virus in vitro was huge step to study the virus
Virus replicates in Hepatocytes
Virus is latent/or replicating in other cells
HCV leads to
Liver failure
Cirrhosis
- irreversible scar
- jaundice because of bilirubin
Carcinoma
Chronic Infection
treatments
- interferon (trigger immune system)
- possibly serine protease inhibitor
- possibly polymerase inhibitors |
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Term
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Definition
Hepadnavirus (not flavi like HCV)
DNA
enveloped
involves reverse transcription
has 4 transcripts
- Core protein or "e" antigen
--the antibody is made against this
- L,M,S surface Antigens
-- Large middle and small (envelope)
- X protein
- DNA polymerase
Don't know how this thing gets in cell and nucleus, but it does
Covalently Clothed Circular DNA is found in Nucleus, and it doesn't go away
Funky stuff happens on its way out of the cell
Has RNA, which is reverse transcribed to DNA, and DNA to DNA
***drugs can block the reverse transcription of RNA, or the DNA to DNA polymerization, or block priming of transcription
Mucous membrane exposures
- parinatal --develop chronic hepatitis B
- sexual activity
- blood transfusions (screened)
Immune tolerant phase: high replication (*serum HBV DNA levels are more directly related to HCC and cirrhosis than ALT levels, so this is important), normal ALT level
Immune Active phase: decrease HBV DNA levels, Increased ALT (liver tissue inflammation or death)
Inactive Carrier phase: complete antigen clearance and seroconverion (antibodies against HB-e formation), ALT normalizes
Reactivation phase: has diseases |
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Term
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Definition
Not a virus alone
encodes ribosyme, two antigens
HDV can't cause problems alone, but in presence of HBV, HDV and HBV is worse
--goal--clear HBV |
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Term
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Definition
a pico-rna
small RNA, non-enveloped,
+ ss rNA
the acute hepatitis
incubation period is 3-5 weeks
shellfish, oral-fecal, sewage |
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Term
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Definition
+ ss RNA
like calicviruses
rural contaminated water |
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Term
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Definition
Reo family
--rotavirus
DOUBLE layered CAPSID
- capsid core for RNA synthesis
- outer capsid cleaved to make Infectious Subviral Particle
DOUBLE-stranded RNA with 11 segments
- nucleus not involved in its replication
fecal oral, and fomites (furniture, toys, etc...)
95% children world-wide will have it by 3-5 yrs old
- 1 million dehydration deaths
pretty common infant diarrhea
-survive acid environment of stomach
-multiply in cytoplasm of enterocytes
----damage VILLI transport mechanisms
viral enterotoxin protein NSP4 promotes calcium influx
causes watery diarrhea, like cholera
--non-invasive, virus, not blood is in the stool
--IgA antibody protects
-vaccine rotarix temporarily on hold (contained live stuff) |
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Term
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Definition
in calcivirus family, like Hep E
naked ss+RNA
Norwalk Ohio Epidemic
prevents absorbtion of water (compromises intestine)
-- not invasive/bloody
--cramps, diarrhea, vomiting, nausea
most common cause of NON-bacterial Gastroenteritis (23 million; 50% of gastroenteritis outbreaks)
Oysters, water, cruise ships, restaurants
wash hands
70% children have Ab by age 7 |
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Term
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Definition
ss + RNA, large, Enveloped, helical
E2 protein on envelope, looks like a cornoa (crown)
L protein makes/copies a negative strand
UPPER respitory tract infections
10-15% caused by Corona
-similar to rhinovirus symptoms
- adults have antibodies, but re-infection is common |
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Term
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Definition
SARS virus, like Corona
species jump from Civets (food in china)
2002-2003 china outbreak cover-up, slowed down international response
--but WHO controlled it, travel restrictions, etc...
atypical Pneumonia
- alveoli TARGET
- death can occur from respitory failure
- blocks oxygen transfer
transmits person to person |
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Term
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Definition
Vaccine is determined by the stuff on the outside of the virus, like the envelope
Vaccines are antigentic without being toxic---they boost the immune defenses by deliberate exposure rather than chance exposure
killed/inactivated with formalin, heat, irradiation
live-attenuated are mutated live virus strains that are not pathogenic to humans, though they are more potent than inactivated |
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Term
| Vaccines for Rhinovirus (a picornavirus) |
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Definition
reasons not to make them:
there are many strains
there is not serious risk of illness or disability
Reasons to make:
large numbers of people
symptoms can be worse in asthmatics
grow well in culture
no animal resvoir
stable wild type
immunity is long lasting |
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Term
| Vaccines for Polio (an entero, picorna virus) |
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Definition
Inactivated Vaccine IPV
inactivated chemically
gets into gut (primary replication)
Antibody stops it at viremia stage
When vaccinated individual is exposed to virus
- becomes a carrier
- antibody stops it in viremia stage
--this is best approach in a vaccinated community
---there is such thing as Herd Immunity, where unvaccinated people are generally protected because the chain is broken -- so you don't have to worry about Carriers, you just have to worry about keeping ''most'' people vaccinated
Live Attenuated (Sabin) Polio vaccine
- grown in cultures, mutant strains survive
- induces antibodies IgA (more than just serum Antibodies) immediately
- gets cleared before it gets into gut (before primary replication stages)
When vaccinated individual is exposed
- nasal, serum, duodenal IgA kills it before gut replication
Note: the live vaccination type 3 may revert back to wild type and be passed to others--it is more potent/effective than inactive form, but also has chance of reverting... (what to do?)
ORAL is best in a non-vaccinated population because type 1, 2, non-reverted 3 mutants can be passed to other individuals and help provide immunity to others
4 countries remain endemic (source)...india, nigeria, pakistan, afghanistan
--need funding, religious, political leaders, soccer player commercial to help get vaccine to people and convince them to have it done
travellers recommended to have vaccine
*interesting, polio type 2 was eliminated; in 2005 polio 1 and 3 were targetted monovalently and quickly stopped transmission in egypt and parts of india |
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Term
| Vaccines for Alphavirus (Toga) |
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Definition
High risk people are vets, zoo keepers
Inactivated Vaccines: EEEV, WEEV, and VEEV
Live attenuated for VEEV |
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Term
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Definition
Yellow Fever
Live vaccine RECOMMENDED for some travelers
Japanese Encephalitis
inactivated and live attenuated
Dengue antibodies (fc receptor) increase the severity of a later infection; so making a vaccine would be difficult if not counter-productive |
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Term
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Definition
MERCK's Gardisil (2005/6)
- HVP types 16, 18 (70% cervical cancers)
- L protein EMPTY Capsid Protein (without the genome)
- it also picks up the HPV 6,11 (ano-genital warts)
- remember HPV can be latent for a long time, boosters needed; efficacy still to be seen...
(2009) approved for Males to prevent Genital warts (HPV 6,11)
(2009) Cervarix approved for women (HPV 16,18) --stronger, more sustained response (uses adjuvant system to help it, aluminum OH MPL)
HPV 3 injection costs $391 (moral obligation to deliver to developing countries?)
--House Bills in government to Raise Awareness in Insurance and schools about this vaccine (people age 9-26 can get vaccinated, but under 18 need parental consent) |
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Term
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Definition
Influenza (- RNA, enveloped, unusual in that Nucleus is required for replication)
Antigenic Drift (point mutations, epidemics) means we need new vaccine each year
Killed (non-live) vaccine - reformulated based on the three antigenic types circulating the previous year (2 type A, 1 type B)
Also a live vaccine (nasal spray)
- flu mist
- for seasonal flu
- since it is live, it has side-effects
- limited to ages 2-49
Universal Vaccine is in development (target the Conserved region of HA (the fusion part--could be effective against mutliple subtypes of flu)
People are also trying to use Cell cultures instead of Eggs for faster supply... for pandemic prevention vaccine
H1 flu vaccine seem to be working for swine H1
possible genetic approach -- just deliver the DNA that codes Hemagglutinin and let the antibody and CTL's build up a response, add cytokines to enhance the response, with NO risk of infection; or just make the virus genome and mutate or take out the pathogenic stuff |
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Term
| Vaccines for HSV (Herpes simplex virus) |
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Definition
None
info about herpes
herpes ds linear DNA, enveloped
latent in trigeminal (oral HSV 1), sacral (genital HSV 2), (vericella is different than herpes, but has latency in dorsal root zoster (shingles) reactivation)
No vaccine for EBV, HIV, HSV, and common cold viruses (rhino/corona?) |
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Term
| Vaccines for Vericella-Zoster |
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Definition
Live attenuated vaccine admistered after 2 yrs. old; also being administered to adults - live attenuated vaccine becomes a latent infection (was hard to approve of), but it is better to have the immunity early rather than suffer the real infection later
**T-cells prevent the re-activation, limit the consequence of reactivation to the skin
As T-cell immunity declines with age or stress, Incidence of Herpes Zoster (reactivation) goes up
There is a Herpes Zoster Vaccine T cell Booster for older people, but it is $162 expensive |
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Term
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Definition
| no vaccine for EBV, CMV or Herpes SV |
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Term
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Definition
HCV
(flavi,ss +RNA, NTR, only in cytoplasm, 5' structural proteins, autoprotease cleavage, ser protease, liver target, jaundice bilirubin, cirrhosis, treatment with interferon)
*Vaccine is difficult because HCV goes into cell and comes out differently
- chronic pathologies are usually difficult to vaccine against |
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Term
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Definition
Hep B (DNA enveloped, covelently clothed DNA immovable in nucleus, weird reverse transcription RNA-DNA-DNA on way out; 4 phases, initial viral D.N.A. levels are important)
Vaccinations have been a Success
acute hepatitis B incidence gone way down 1987-2006
-- the vaccine is an example of a more recent approach--the subunit vaccine
-- the subunit vaccine is not a virus, just the antigenic subunit parts for the specific surface Antigen "HBsAg" on Hep B |
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Term
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Definition
hep A (pico-rna)
oral-fecal sewage shellfish
travelers vaccinated |
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Term
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Definition
Vaccine for Rota in 1998 withdrawn due to bowel blocks in infants
Rotateq and Rotarix (RV5, RV1) are approved now
- DNA fragments from pig found in Rotarix, not suspended, but recommended not to give it |
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Term
Bacterial Vaccines
Bacterial Toxin Vaccines |
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Definition
BCG from bovine, provides protection against Mycobacterium tuberculosis
attenuated strain for Salmonella typhi, provides protection against typhoid fever
Toxins from Corynebacterium diphtheriae
Toxins from Clostridium tetani
change these, with fomalin, into toxoids
DTP -- Diptheriae toxoid, Tetani toxoid, KILLED pertussis cells--helps with response to toxoids as well
DTaP (more expensive) - Diptheriae toxoid, Tetani toxoid, acellular pertussis components
TdaP - less diptheriae toxin, less side-effects
*TdaP given to old people who work with kids
(Jeff Gordon - adults need boosters)
TdaP IPV - includes inactivated polio virus |
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Term
| Bacterial polysaccharide Vaccines |
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Definition
kids under 18 don't have great T-independent response (happens in polysacharide/bacterial response), so they need to see an antigen (tetanus or diptheria toxoid) coupled to the polysaccharide so that they can have a T-cell-dependent isotype switching, full-blown response (CD40L T to CD40 B)
Neiserria meningitis: severe damage
- required vaccine for college dorms (this is the one they wanted us to get living on campus)
Menomune - didn't last long, just the polysacharide
Menactra/Menveo - last longer, conjugated poly/oligo sacharide to diptheria toxoid
Haemophilus influenza b (Hib) meningitis
non-conjugated was not effective
conjugated (1987) was effective
Streptococcus pneumoniae
-Pneumovax,prevnar,prevnar 13(13 serotypes covered)
---companies making these lead to shortages if they don't want to make them --issue that we have to deal with |
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Term
| Four rules about Virus Envelopes/capsid types |
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Definition
All DNA are Icosahedral (except POX)
All DNA are Naked (except the enveloped ones: Hep B, Herpes viruses, and Pox)
Small Icosahedral RNA's are Naked (except Toga and Flava which have envelopes)
All helical RNA are enveloped
*Retroviruses are neither icosahedral or helical, but they are enveloped
**Pox is DNA, not icosahedral, and enveloped
Summary of enveloped
DNA
-Hep B
-Herpes virus
-Pox
RNA
-All helical are enveloped
-Toga
-Flavi
-Retro |
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Term
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Definition
Rupintrivir
Rhino is a picorna
(VAP is canyon, cytocidal, ss+RNA makes viral self-cleavage protease)
Rupintrivir inhibits the protease |
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Term
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Definition
Amantadine: M2 ion channel blocker (M2 allows H+ into virion, H conformation, fusion, release RNP
---most viruses are resistant
NA inhibitors: block NA from cleaving Sialic Acid and thereby blocks virus from being relased from Cell
(- ss RNA segmented genome (unusual for RNA to replicate in nucleus, but influenza does), short RNA coming from nucleus blocker is in development)
influenza type A traditionally, 2008 H1N1 flu
-Amantadine/Rimantadine (M2 inhibitors)
Influenza B, Influenza type A in 2005-2006, 2009 (swine flu) to present
-Oseltamivir and Zanamivir (NA inhibitors) |
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Term
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Definition
2 Entry/Fusion inhibitors (TransMembrane Env, etc...)
--Enfuvirtide (T-20 Fuzeon) Fusion inhibitor
--Maraviroc (Binds CCR5 on CD4's; if CXCR4 is available in patient, drug won't work)
12 Reverse Transcriptase Inhibitors
(tRNA is sitting on neg RNA, waiting for reverse transcriptase)
-- Zidovudine/AZT (first of Nucleoside RT Inhibitor)
-- Chain terminator
--1986 wonder drug, resistance followed
--now there are more (abacavir, tenofovir, epivir, etc...all Nucleoside/chain terminators can cause fatal acidosis
-- Non-nucleoside RT inhibitors (not like nucs)
---nevirapine, delavirdine, efavirenz, etravirine(2008)
1 Integration Inhibitors
(integrase)
Raltegravir (strand-transfer Inhibitors)
10 Maturation Inhibitors
(protease cleavage of Gag; influenza cleaves H for maturation/fusion)
--10 FDA approved (POTENT, but resistance is rapid if used alone)
people are working on attachment (SU protein), getting in (PIC) and out of the nucleus (env, gag)
Viral Load is Important *Viral load is the speed of the train towards the cliff. CD4 T-cell number is the distance to the cliff.
High levels of replication, 10 billion new varions/day ---Mutants already exist before therapy---you must use three or four drugs to lower viral load/antigens (HAART--highly active anti retroviral therapy) |
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Term
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Definition
Interferon
- binds cell receptor
- induce antiviral state in cells
- inhibit/breakdown viral RNA
peg-interferon
- lasts longer
Nucleoside Analogs
- inhibit the Polymerase, not toxic, but disease comes back with avengence
- Lamivudine 70% resistant
- Adefovir 29%
- Telbivudine 22%
- Entecavir 1.5%
- Tenofovir
Entecavir, Tenofovir block, among other polymerase function, reverse transcription
HBV Antiviral therapy
- Serum HBV DNA levels are important indicators of HCC and cirrhosis development -- to improve underlying hepatic problems
- the outcome or goal is to lower the level of HBeAg or HBsAg antigens |
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Term
| Herpes Simplex and Vericella-Zoster Anti-virals |
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Definition
Herpes, VZV chickenpox/shingles
Acyclovir
most effective against HSV-1 (encephalitis, oral) > HSV-2 (sacral) > VZV > EBV > CMV(not at all)
- The HSV Thymine Kinase is much more (3000 times) likely to phosphorylate the Acyclic G Base than a normal cell
- The host cell completes the phosphorylation to Tri-P
- acyclic (without Ribose, without 3' end) G gets incorportated and terminated DNA strand -- it inhibits Viral DNA polymerase
Herpes
Acyclovir acts against genital herpes (HSV-2), prevents death in Herpes Encephalitis (HSV 1)
if you need higher levels
--Valacyclovir (a prodrug of Acyclovir)
--Famciclovir (different dosage, similar purpose)
IF HERPES is resistant to Acyclovirs
-----use Foscarnet (nephrotoxic)
VZV
acyclovir helps with shingles (at least ophthalmic)
If resistant to Acyclovir
----use Foscarnet |
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Term
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Definition
CMV retinitis (seen on eye exam)
Valgancyclovir (prodrug for Gancyclovir)
Ganciclovir
- covers CMV >(also covers HSV, VZV)
- Toxic
If resistant
------use Foscornet (nephrotoxic) |
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