ICL 1.1: Intro to Viruses Flashcards
What are the 3 components of medical virology?
- infectious agent
- health interventions
- host defenses
what are the categories of infectious agents?
- viruses
- bacteria
- fungi
- protozoa
- animalia
what is a virus?
obligate intracellular parasites
small, obligate intra-cellular parasites, possessing either a RNA or DNA genome and a receptor-binding protein (capsid/coat) allowing entry into cells
where do viruses replicate?
they replicate only inside the living cells
this is because they use the cellular synthetic machinery for transcription, translation and replication to cause the synthesis of specialized elements called virions that serve to transfer the viral genome, which can be either RNA or DNA, to other living cells
if you put a virus in a petri dish, nothing will happen!
is the viral genome RNA or DNA?
DNA or RNA: it can be either!!
viruses use cellular machinery to synthesize virions that serve to transfer the viral genome, which can be either RNA or DNA, to other living cells
**there are no bacteria with RNA genomes
what is the infectious form of a virus called?
virion
virions are either enveloped or non-enveloped (naked)
what are the 2 distinct stages/forms of a virus?
- non-infectious form = virion
2. non-infectious form of virus = intracellular form of virus represented by its genome
what are the components of a virion?
- genome
- capsid
- matrix
- envelope
what are the two types of virions?
virions are either enveloped or non-enveloped (naked)
enveloped viruses are sensitive (inactivated) to
organic solvents, detergents
what inactivates enveloped viruses?
enveloped viruses are sensitive/inactivated to organic solvents/detergents
what is the capsid of a virion?
a protein shell that surrounds the genome
the RNA and DNA need to be protected so viruses make a protein shell to protect it
a capsid can have many shapes!
what are the types of capsidss?
- cubic (icosahedral)
- helical
- complex
what is the matrix of a virion?
matrix proteins are extra proteins put into the virus that help with infection or boost the replication cycle
they’re proteins inbetween the capsid and the envelope
not all viruses have a matrix!
what is the envelope of a virion?
its a lipid bilayer with a glycoprotein external layer surrounding nucleocapsid
enveloped viruses have a lipid bilayer outside the capsid protein that contains the viral envelope proteins (these have receptor-binding functions)
some viruses have envelopes and others don’t – viruses without envelopes are called naked
so it goes genome –> capsid –> envelope from inside out
what is a nucleocapsid?
genome + capsid
can you tell which virus something is from the microscope image?
not always
sometimes the image is diagnostic like with HIV because it’s really distinct
but other times you can’t because like influenza looks like Ebola
so images can be helpful but not always
what is the name of the viral structure composed of
the genome enclosed in a protein coat?
nucleocapsid
genome + protein shell
the nucleocapsids of viruses without envelopes are the virion structures of these viruses (also called naked virions)
list the DNA virus families
SMALLEST
1. parvoviridea
- polyomaviridae
- papillomaviridae
- adenoviridae
- ————————— - herpesviridae
- poxviridae
BIGGEST
1-4: naked
5-6: enveloped
which DNA virus families are naked virions?
- parvoviridea
- polyomaviridae
- papillomaviridae
- adenoviridae
which DNA virus families are enveloped virions?
- herpesviridae
2. poxviridae
what are the categories of RNA viruses?
- positive RNA
- double-stranded RNA segmented
- negative RNA
which virus families are positive RNA viruses?
- picornaviridae
- caliciviridae
- hepeviridae
- ————————- - flaviviridae
- togaviridae
- coronaviridae
1-3: naked
4-6: enveloped
which virus family is a double-stranded RNA segmented virus?
reoviridae
it’s a naked virus!
which virus families are negative RNA viruses?
MONONEGAVIRALES
1. rhabdoviridae
- paramyxoviridae
- filoviridae
- bornaviridae
SEGMENTED
5. orthomyxoviridae
- bunyaviridae
- arenaviridae
**these are all enveloped virions!
which virus families use reverse transcription?
- hepadnaviridae
- retroviridae
they make DNA from RNA! they encode a reverse transcriptase
retroviruses have an RNA genome and make DNA on the way in (first step after uncoating)
hepadnaviruses have a DNA genome and make DNA on the way out (last step during assembly)
what is the difference between positive RNA and negative RNA viruses?
positive strand RNA viruses are positive sense RNA so they match mRNA and can be directly translated into proteins
negative strand RNA viruses are negative sense RNA so they have to make mRNA before they can make protein
are most RNA viruses single or double stranded?
single
there’s only one double stranded: reoviridae
virus classification table
slide 12
which capsid symmetry do DNA viruses have?
DNA viruses have icosahedral symmetry
except Poxviruses that have complex symmetry
which capsid symmetry do positve stranded RNA viruses have?
positive stranded RNA viruses have icosahedral symmetry
except coronaviruses which have helical symmetry
- picornaviridae
- caliciviridae
- hepeviridae
- ————————- - flaviviridae
- togaviridae
- coronaviridae
1-3: naked
4-6: enveloped
which capsid symmetry to negative stranded RNA viruses have?
all negative stranded RNA viruses are enveloped and have helical symmetry!
which type of capsid symmetry do reoviruses have?
they have multiple capsid shells
they’re naked virions!
what capsid symmetry do the reverse transcriptase viruses have?
- hepadnaviridae
- retroviridae
they both are enveloped and have icosahedral symmetry!
what are the replication steps that have to happen for every virus?
- adsorption/attachment
- penetration
- uncoating
- synthesis
- assembly
- release
penetration + uncoating = entry
what happens during the attachment phase of virus replication?
the virus must bind to a receptor on a host cell
the virion has some protein that can bind to the receptor on the host cell
if the virion has an envelop, then there’s proteins on the envelop that will bind to the host cell – if it’s a naked virus then proteins directly on the capsid will bind to the host cell
VAP = viral attachment protein on virion
how can we prevent virus attachment?
if we can stop the virus from binding to the cell then this would be great!
we can make neutralizing antibodies or mAb that prevent the virus from binding to the receptor and stop it from the beginning
what is VAP?
VAP = viral attachment protein on virion
VAP is a capsid protein for naked viruses or it can be an envelope protein for enveloped viruses
at what temperature will virion attachment occur?
4 °C
what determines the tropism of a virion?
the binding of a VAP to the host cell receptor will define tropism of the virus
if a certain cell or species doesn’t have a receptor on their cell then the virus can’t infect their cells!
so maybe a virus can only infect liver cells but not neuron cells because they don’t have the virus receptor
what happens during the penetration phase of virus replication?
it’s the process by which the virus is taken up into cells
the actin cytoskeleton is involved in all endocytotic pathways! it’s used to shuttle the virus around once it gets into the cell
two general types:
1. occurs at cell surface = pH independent
- occurs inside, after receptor-mediated endocytosis = pH dependent
what happens during pH dependent penetration?
the virus enters the cell in an endosome and requires a specific pH trigger to allow for uncoating of the genome
it will then use the pH in the endosome to start disassembling the virion
as the cell moves along the actin cytoskeleton, the pH of the endosome will change as it matures which will help the virus with uncoating
what happens during the uncoating phase of virus replication?
uncoating is the separation of the genome or internal nucleocapsids from the outer structural components of virions
in some cases it is difficult to separate penetration from uncoating, both occur simultaneously
you need to take the nucleocapsid apart so that you can translate the genome and make viral proteins
what is the eclipse period?
it results from uncoating
at this point you’ve disassembled the virion because you’ve removed the envelope and capsid
if you tried to measure the virus in the cell right this moment, you wouldn’t detect anything!!
the person is still infected but there’s no virus present because you’ve uncoated it and haven’t yet replicated anything – all the components are being made at this point before assembly
what happens during the synthesis phase of virus replication?
synthesis phase starts after uncoating
the virus genome directs the cell to synthesize “nonstructural” & “structural” proteins and more genomes
the virus is trying to make viral proteins to copy more genomes and make proteins to synthesize new virions – so the virus takes over the cell and and the cell is now only making viral proteins
how the virus accomplishes this task depends on the “replication strategy of the virus”
what’s the difference between structural and nonstructural proteins?
structural proteins = proteins found in virion particles (ex. capsid)
nonstructural proteins = proteins produced in infected cells but not found in virions
nonstructural proteins just get used during replication but don’t get packaged into the virion - usually they’re enzymes that can replicate the virus but are not needed for infection
what happens during the assembly and release phase of virus replication?
during assembly, the virions are formed by packaging the genomes with capsid proteins
and if the virus is enveloped, wrapping the nucleocapsid in an envelope
naked viruses accumulate in the cell and are released when the cell dies
enveloped viruses acquire their envelope by budding through a membrane of the cell and are also released in the same step
what is budding?
the process by which a virion acquires an envelope
aka it only happens with enveloped virions!
budding occurs at the plasma memebrane OR internally at the golgi, ER, nuclear membranes etc. and is specific to each virus
there are matrix proteins that recruit the genome to a specific intracellular part of the plasma membrane – the matrix proteins help the virus to associate the nucleocapsid with a specific site on the membrane that facilitates the budding process
then at the end of the budding process, there are viral proteins involved to snip the connection with the cell so the virus is released
what is a PFU?
PFU = plaque forming unit
one virus can infect a single cell, spread and kill surrounding cells to cause a plaque (a clear area of dead cells) surrounded by live cells
explain the hyperbolic growth of a virus?
immediately after infection, there’s absorption, penetration, uncoating
then there’s the eclipse period where the cells are infected but we wouldn’t find any virions
during this time we’re making viral proteins and synthesizing stuff and then all of a sudden you get a huge spike because eventually all the virions are released at once once the cell can’t support the virus anymore
what determines the viral replication strategy?
the viral genome!!
the genome is the most important determinant; it’s what determines what the virus has to do in the cell to replicate
what the virus has to do to make mRNA to eventually makes proteins is different for RNA vs. DNA viruses
what determines tropism of a virus?
VAP-receptor interaction
what is a transient virus infection?
when the virus is cleared due to immune responses
what is a persistent virus infection?
the virus isn’t cleared by the immune response even if the immune response is fully active
- chronic
- latent
- recurrent
what is a chronic virus infection?
infectious virus is continuously present
what is a latent virus infection?
the virus genome is present in cells but not infectious virions
what is a recurrent virus infection?
a latent infection that reactivates and yields infectious virus before becoming latent (non-replicating) again
what is a slow virus infection?
a chronic persistent infection with a prolonged incubation period of months to years and in which the disease symptoms progressively worsen to death
how does the immune system clear viruses?
- virus-specific antibodies
- virus-specific T cells
virus-specific antibodies “neutralize” or remove virus particles from blood or respiratory secretions, while virus-specific T cells eliminate virus infected
cells, preventing persistence of the virus and of disease
what do virus-specific antibodies do?
- block receptor binding (neutralizing antibodies)
- bind virus and prevent uncoating (entry blocking antibodies are neutralizing)
- bind virus and remove coated virus particles via phagocytosis
- may require complement to neutralize certain viruses
what do virus-specific T cells do?
they kill virus-infected cells when they recognize virus antigens on cell membranes kill infected cells that present viral peptides using MHC I
how do viruses cause disease?
- they kill cells and result in organ failure
- immune reaction to virus infection
- virus infection induces autoimmune disease
- congenital infection prevents or distorts organ development
- virus infection provokes inflammatory state
- virus infection induces an immunodeficient state
what are some undifferentiated symptoms of viral infections?
fever
myalgia
malaise
anorexia
these symptoms occur after the host has responded immunologically and virus often is no longer present
