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virology: ch 13, 20.6 &27 (HIV/AIDS sections only)
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what family is SARS-COV-2?
Beta Corona Virus
is SARS-COV-2 enveloped or unenveloped?
enveloped
what is a unique feature of SARS-COV-2
it contains a unique spike glycoprotein that gives allows it to invade other cells, specifically, those containing the ACE2 receptor
where can ACE2 be found in the human body?
human ACE2 receptors are commonly found in the epithelium cells in the respiratory and digestive tract
what organ does SARS-COV-2 target + outcome
COVID-19 primarily goes after the respiratory system, where ACE2 receptors on cells are predominant. the virus replicates in the respiratory tract. once it makes it way to the lungs, the virus can cause apoptosis of infected pneumocytes, spread alveolar damage, weaken and cause capillaries to leak, and impair gas exchange
4 COVID-19 omicron + variants characteristics
higher transmission (more infectious)
decrease in people losing sense of taste/smell
vaccinated population is more likely to experience symptoms
less likely to cause severe symptoms
what tests are used for current covid-19 infections?
RT-PCR: most accurate because it detects RNA genome of virus using reverse transcriptase (RNA → DNA) and amplifies DNA for detection
Antigen test: detects viral proteins using ELISA, false results may show up when low levels of virus (early stages of infection) are present.
covid-19 test used for previous covid-19 infections
antibody tests: use the ELISA format to detect antibodies against covid-19, highly specific and results indicate if you were previously infected because antibodies take a while to develop
regeneron
“cocktail” treatment used against early stages of covid-19 infection. contains monoclonal antibodies that work against the spike protein
paxlovid
pfizer: oral antiviral obtained through prescription that inhibits viral replication prior to severe symptoms/disease of covid-19
molnupiravir
merck: oral antiviral prescribed to pt w/ covid-19 before severe symptoms/disease, works by causing RNA to mutate
how do mRNA vaccines work against covid-19
vaccines cause human cells to express spike so that the immune system develops anti-spike Ab
pfizer and moderna
how do new variants impact vaccine efficacy?
variants often contain mutations and changes to spike proteins that the antibodies developed by the vaccine cannot recognize
what are some general characteristics of viruses
viruses are non-living entities and can infect all lifeforms, they are commonly referred to by the organism they infect (bacteriophage). viruses are also self assembling
T/F: viruses are organisms
false
viruses are technically not considered to be ‘alive’ bc they cannot live/replicate independently w/o a host cell. viruses are just nucleic acid surrounded by protein and lack organelles
virion
a virus particle consisting of nucleic acid surrounded by capsid
naked virion
do not have envelope
enveloped virion
surrounded by lipid membrane, may contain matrix proteins, only found in eukaryotic viruses
capsid
protein coat made of capsomers that enclose nucleic acid
icosahedral symmetry
most common virus shape, contains 20 isometric (equilateral flat surfaces)
pleomorphic/complex viruses
most phages are this kind with an isometric head + long helical sheath/tail and helical or rod like appearance in the virion
nucleocapsid
viral capsid together w/ nucleic acid that is packed w/n protein coat
what do attachment proteins/spikes and tail fibers do
mediate attachment to the host
do viruses contain RNA and DNA?
no, they either contain DNA or RNA, not both
what is the structure or viral genomes?
linear or circular and can be single or double stranded
what do viral genomes encode for?
viral protein coat
assure replication of viral nucleic acid
movement in/out of host
enzymes not present in infected cell
viruses in the extracellular phase are metabolically ______
inert
viruses in the intracellular phase are metabolically ______
active
lytic cycle
phage lyses host cell and takes over metabolic processes of cell
non-lytic cycle
phage extrudes out of infected cell (filamentous phages) and only partially take over cellular metabolic processes
lysogen
bacteria carrying viral DNA
lysogenic state
virus is integrated into chromosomes/DNA of hose and replicates w/ it, also called temperate phages
lysogenic conversion
viral DNA modifies properties of bacterium- toxin production
what are the 6 stages of lytic cycle?
attachment/adsorption
penetration
replication
assembly/maturation
release
attachment
protein fibers located at the end of the phage’s tail attach to specific receptors on the host cell’s cell wall
penetration (plant/bacteria viruses)
phage injects nucleic acid into host cell through the cell wall by degrading portion of cell wall to create a hole using lysosyme, phage coat remains outside cell
penetration (animal viruses)
entire phage is able to go through cell wall since animal cells lack rigidity and is engulfed by the cell via phagocytosis and go into uncoating step to release nucleic acid from capsid
enveloped viruses: undergo membrane fusion and fuse to the plasma membrane of the host cell to phage’s envelope
transcription
phage DNA is transcribed into mRNA and then proteins
replication
new copies of phage particles are produced and protein. is synthesized
in this stage the phage will also inhibit activity of the host DNA by producing enzymes to destroy host DNA
assembly/maturation
DNA is packaged in phage head protein and components come together to form matura phage
release
intracellular phages release enzyme to digest host cell wall (cell becomes lysed) and viruses are released
eukaryotic/animal viruses: as phages leave host cell, envelope is picked up as envelope is made of a portion of host cell plasma membrane and becomes lipid envelope of virus
lytic ssRNA phages
MS2, Qβ
only infect F+ strains of E.coli and attach to the sides of sex pilus, replicate rapidly (~ 10,000) and requires RNA dependent RNA polymerase that must be encoded on entering phage RNA
phage λ (lambda)
most phages 90% temperate phages and can occur is slow growing bacteria and become prophage
e.coli phage that binds to very specific spot in host DNA strand (homologous match")
prophage
integrated phage DNA
lysogenic cell/lysogen
bacterial cell carrying prophage
lysogenic conversion
phage DNA codes for proteins that modify cell properties
what is the difference between the lytic and lysogenic cycle?
in the lysogenic cycle, the phage DNA is not immediately transcribed and replicated like in the second stage of the lytic cycle. instead, the viral nucleic acid integrates itself into a specific part of the host’s chromosome. the host continues to replicate with the phage’s DNA, passing it onto progeny. this occurs until induction
induction
step in lysogenic cycle where host cell is exposed to UV or a chemical (from a lab) that ‘activates’ phage DNA to excise and enter lytic cycle as normal
phage repressor
binds to phage operator to inhibit expression of excision and lysis genes, also inhibits infection of cell w/ phage of the same type and replication
if repressor stops being made or is inactivated, excisase is produced = phage DNA excises, reproduces and lyses cell
ssDNA filamentous phages
infect only F+ strains of E.coli and attach to tip of sex pilus. phages go inside of cells and just replicate, they do not lyse the cell
transduction
DNA is transferred from one bacterial cell (donor) to another (recipient). can sometimes encode resistance genes
generalized transduction
via generalized transducing phages- virulent and temperate phages. can be any gene of donor cell. transducing phage is defective bc it lacks viral DNA necessary to form complete phage and lyse recipient cell
specialized transduction
via specialized transducing phages- only temperate phages. transfer only a few specific genes
host ranges
number of different bacteria a phage can infect
limiting factors to hose ranges
host receptors: most phages are specific, ex: phage lambda only infects E.coli
must overcome host restriction modification system
alteration of host cell receptors
mutation
lysogenized bacteria can alter cell surface resulting in alteration of receptor site
restriction modification system
restriction enzyme: codes for endonuclease, cuts small segments of viral DNA when recognized
modification enzyme: attaches methyl group to DNA flagged by restriction and will not be recognized later on, protecting cell’s own DNA
phage therapy
use of bacteriophages as antibacterials to treat pts
phage lysins as antimicrobials
use of phage enzymes to treat infections as opposed to whole phage
CRISPR
clusters of regularly interspersed short palindromic repeats
phage spacer DNA inserted into CRISPR, providing record of infection. small RNAs bind to Cas (CRISPR associated sequences) proteins and bind spacer RNA to phage, targeting phage for destruction
enteric viruses
generally fecal-oral transmitted, often cause gastroenteritis, some cause systemic disease
respiratory viruses
transmitted via droplet, generally localized in respiratory tract
zoonotic viruses
transmitted via animal → human via animal vector
sexually transmitted viruses
can cause genital lesions or systemic infections
herpesviridae
herpe simplex: enveloped, double stranded DNA virus
hepadnaviridae
hepatitis B: enveloped, double stranded DNA virus
papillomaviridae
HPV: non-enveloped, double stranded circular DNA
polyomaviridae
non-enveloped, double stranded circular DNA
adenoviridae
cold, conjunctivitis: non-enveloped, double stranded linear DNA virus
parvoviridae
canine parvo: non-enveloped, single stranded DNA virus
poxviridae
smallpox: enveloped, complex DNA virus
flaviviridae
dengue/zika: enveloped, icosahedral, positive sense, single stranded RNA virus
togaviridae
enveloped, icosahedral, positive sense, single stranded RNA virus
retroviridae
HIV: enveloped, icosahedral, positive sense, single stranded RNA virus
*replicates in nucleus
coronaviridae
SARS COV2: enveloped, helical, positive sense single stranded RNA virus
picornaviridae
common cold: non-enveloped, icosahedral, positive sense, single stranded RNA virus
caliciviridae
non-enveloped, icosahedral, positive sense, single stranded RNA virus
orthomyxoviridae
influeza: enveloped, helical, negative sense, single stranded RNA virus
*replicates in nucleus
paramyxoviridae
measles: enveloped, helical, negative sense, single stranded RNA virus
rhabdomyxoviridae
enveloped, helical, negative sense, single stranded RNA virus
filoviridae
ebola: enveloped, helical, negative sense, single stranded RNA virus
bunyaviridae
enveloped, helical, negative sense, single stranded RNA virus
arenaviridae
enveloped, helical, negative sense, single stranded RNA virus
reoviridae
rotavirus: non-enveloped, icosahedral, negative sense, double stranded RNA virus
acute infections
short lived infections, produce large number of viruses during infection (productive)
ex: covid-19, flu, cold
persistent infection
host never really gets rid of virus, may remain dormant (latent), active (chronic), or slow
latent infections
periods of no virus (asymptomatic) and reactivate later
ex: HSV-1 (herpes) - on/off resurgence of sores activated by stress. virus binds to nerves along posterior cervical region and travel down to ‘active sites’ (mouth, genitalia), revealing sores
chickenpox- shingles reactivates chickenpox
chronic infections
symptoms always present due to constant high levels of virus
ex: HBV
slow infections
virus replicates over long period of time, presenting dieases “late”
ex: HIV
first mechanism of enveloped viruses
Virion attached to host cell receptors w/ specific protein spikes
Viral envelope fuses w/ host cell plasma membrane
Viral nucleocapsid is released directly into cytoplasm
Nucleic acid separates from protein coat (capsid)
second mechanism of enveloped viruses
Enveloped virus adsorps into host cell w/ specific proteins
Virion taken in to cell via endocytosis
Host cell plasma membrane surrounds entire virion- forming a vesicle
Envelope of virion fuses with plasma membrane, pH needs to be lowered
Nucleocapsid is released into cytoplasm
Capsid is removed, releasing viral nucleic acid
naked virus mechanism
Enters cell via endocytosis, does not fuse with plasma membrane
Viral nucleic acid is released from endocytic vesicle by dissolving it
Nucleic acid separates itself from capsid
viral growth cycle
attachment + penetration of parental virion; endocytosis → membrane fusion → vesicle escape (naked virus)
uncoating of viral genome; nucleic acid released into cytoplasm or nucleus
early viral mRNA + protein synthesis; early proteins (enzymes) used to replicate viral genome
viral genome replication
late mRNA + protein synthesis; structural, capsid proteins
progeny assembly
virions released from cell
⊕ stranded RNA virus replication
make proteins immediately upon entering host cell, requires ⊖ template strand, occurs in cytosol
⊖ stranded RNA virus replication
go through intermediate for both to make new viruses, occurs in cytosol
DNA virus replication
HAVE to get inside nucleus to replicate, transcription machinery creates messages that are relayed in/out cytosol for proteins to make replicates
viral mRNAs contain
methylated GTP cap
poly A tail
mRNA generated by splicing
how do some viruses make more than one type of RNA from one piece of DNA?
shifting of reading frame
temporal control of transcription from DNA viruses
repressor protein prevents/postpones transcription of some genes