introduction to viruses Flashcards
virus
invasive biological agent that reproduces inside the cells of living hosts
contain only one kind of nucleic acid (DNA or RNA)
replicate by synthesis then assembly of component parts
virion
the extracellular infectious virus particle
consists of viral nucleic acid with a protein coat
some have outer lipoprotein membrane envelope
usually small (20-300 nm in diameter)
obligatory intercellular growth
physical virion particle is just a vehicle to transport nucleic acid from cell to cell
must be within a cell to replicate because need the cell’s machinery
replication of viruses
don’t multiply by binary fission - rather by synthesis and then assembly of component parts
eclipse period
when virus infects cell the virion proteins covering the nucleic acid are uncoated and the original virion particle is not recognizable - between this period and when detectable virion is present = eclipse period
nucleic acid in virons
have only one kind
either RNA or DNA
can be single-stranded, double-stranded for both DNA or RNA
replication cycle of viruses (list of steps)
adsorption (need specific host cell receptor)
penetration (entry)
uncoating (eclipse period begins)
synthesis of virus parts (nucleic acids and proteins)
assembly of new virions (eclipse period ends)
maturation (virions become infections - usually involves a virus or host enzyme)
release
what the cell supplies the virions for cell growth (5 things)
- machinery for translation of viral mRNA into viral proteins (ribosomes, t-RNAs, etc.)
- energy (ATP)
- low molecular weight precursors (nucleotides and AA)
- various host cell enzymes or factors required for replication, assembly, maturation, or release
- various cellular transport pathways/machinery
what the virus supplies (3)
- genes for virion proteins
- genes for proteins that do not end up in the virion
- genes for one or more proteins that play a role in the replication of the viral genome and may or may not end up in the virion (depending on the virus)
virus strategy (3 things consistent to all viruses)
- all viruses have a nucleic acid genome packaged in a proteinaceous particle
- genome contains information sufficient to complete an infectious cycle in a susceptible and permissive cell
- all viral genomes establish themselves in a host population
susceptible cells
express a host cell surface receptor the virus needs to use for adsorption and entry
permissive cells
even if can enter cell doesn’t mean can replicate there
to replicate must overcome innate cell defenses and the cell must possess all of the molecules and machinery that the virus requires for completing the cycle
challenges of being a virus (3)
- a virus must encounter hosts and host cells
- a virus must evade or bypass host physical defenses such as skin, mucous layers, etc
- once inside the host, the virus must face host defense mechanisms (cell intrinsic, innate, adaptive) and the virus must overcome these obstacles to successfully propagate and transmit infection to new hosts
capsomers
identical building blocks that make up the protein coat of viruses
arranged in helical or icosahedral shape (solid with 20 faces, 12 vertices, allows formation of closed shell with the smallest number of identical subunits)
nucleocapsid
protein coat of virus
made from capsomers and in a helical or icosahedral shape
smallest icosahedral has 60 sides, all are extremely environmentally stable
can be enveloped or not
formation of nucleocapsid
occurs within infected cells
happens when capsomers recognize viral genome - complexes form between the capsomers and the genome
enveloped viruses
more complex
have lipo-protein membrane surrounding the nucleocaspid
neutralization
inactivation of the infectivity of a virion by antibody that specifically recognizes a protein on the surface of the virion
the only important viral antigens are proteins
capsomers are the antigens in unenveloped (naked) virion
in enveloped virions viral proteins present on the lipid envelope react with neutralizing antibody
antibodies bind tightly and essentially irreversibly to virions
methods for detecting viruses (list)
- cultivation
- cytopathic effect
- infection of tissue culture to detect tumor viruses
- identification of inclusion bodies
- plaques in cell culture
- SYNCYTIA
- immunological methods
cultivation of viruses for detection
in embryonated eggs or susceptible cells
slow and laborious process
can confirm presence of virus but not specific identity
cytopathic effect
change in appearance of cells with respect to size, shape, motility, attachment, or continued existence as a viable cell due to viral infection
to detect, infect tissue with viruses and observe
lytic viruses will rapidly kill host cells when virions released, less lytic ones will not but will still cause phenotypic, observable changes (detectable with light microscope)
transforming viruses
do not cause lysis, death or obvious cytopathic effect on infected host cells in tissue culture but can cause abnormal proliferation of cells in culture so can be detected that way (by light microscope)
inclusion bodies
stain virus infected cells in tissue culture before cells die
sites of viral replication or assembly can sometimes be identified histologically
presence of these bodies and their cellular location may be characteristic of a particular virus
plaques
when viruses have cytopathic effects, can cause zones of dead cells in cell culture
make dilutions of a virus from a clinical sample and measure plaque forming units (PFU)
only method for measuring infectious virions in a clinical sample
syncytia
multinucleated cells developed when some viruses cause cells to fuse together
some enveloped viruses have a fusion protein in their envelope
immunological methods where virion is antigen
via:
- neutralization (see card)
- complement fixation (see immunology lectures)
- hemagglutination and hemagglutination inhibition (described in later lectures)
- fluorescent antibodies (see immunology lectures)
- radioimmunoassay, ELISA, and other sensitive methods
neutralization
when virions are complexed with antibody they’re neutralized - can’t infect
most specific way of conclusively serologically identifying a virus
can measure in PFU assay by measuring reduction in PFU following neutralization
only works on infectious virions
ways antibody tests can be used to diagnose a viral disease (slow methods)
- virus isolated from patient can be identified by immunological methods where virion is used as antigen (see card for this) if there is a known antisera against each of the viruses compatible with the clinical presentation
- titirate paired acute or convalescent sera from patient against known viruses that are compatible with the clinical symptoms = seroconversion
seroconversion
change in antibody status from having no antibody against a certain virus to having the antibody
occurs when testing for viruses in patients
titrate paired acute (before immune response) and convalescent (after immune response) sera from patient against known viruses - one of these known viruses will show an increase in antibody in the convalescent serum sample
patient if seropositive for the virus that shows antibody increase
seronegative if no increased response
window period
when virus should be serologically detected by is not yet detectable because in some viral infections antibody production is unexpectedly delayed for several weeks
ways antibody tests can be used to diagnose a viral disease (fast methods)
- detect viral protein antigens in specimen using a fluorescent antibody
- viral nucleic acid identified in a specimen by PCR
immune response to viruses
two components of response to reinfection: antibody and cell-mediated
antibody response to viruses
antibody mediated response = neutralization
all classes of antibody act in the same way to neutralize virions
antibody has no effect on intracellular multiplication of viruses and may be ineffective in halting the spread of virus from cell to cell when the cells are in close contact
secreted IgA is important defense against viruses that initially infect resp. tract or GI tract
passive immunization
transfer of circulating antibody
can prevent or reduce clinical disease in certain virus infections
simple RNA viruses
all icosahedral in shape
assembled in cytoplasm and make crystals there
simple DNA viruses
all icosahedral
assembled in nucleus and make crystals there
stability of simple nucleocapsids
generally very stable and so direct person to person contact is not required for transmission since they can exist in the environment
host range
species of animal that can be infected by a given virus
determined by adsorption
eg. polio can only infect humans and higher primates
tissue tropism
specific tissues that can be infected by a virus
replication of polio virus genome
RNA genome replicates itself using RNA-dependent RNA polymerase
DNA not involved - specific inhibitor of RNA synthesis on a DNA template prevents the growth of cells and DNA viruses but not picornaviruses like polio
viral RNA made in cytoplasm
inhibits host cell DNA, RNA and protein synthesis
sequence of events in early infection (true for polio at least)
1: viral RNA acts as mRNA with cellular ribosomes to form polysomes - initial product is a very large protein
2: large protein cleaved to yield about 8 functional proteins including capsomer proteins and enzymes for making more viral DNA
3: one of these enzymes (an RNA dependent RNA polymerase) uses the RNA of the infecting virus as a template to make complementary (minus-stranded) RNA which can then be the template for more plus-stranded RNA
4: the molecular species actually involved in virion RNA synthesis is the replicative intermediate (a minus strand with several “growing” strands of viral RNA attached to it)
plus-stranded RNA virus
one whose virion RNA can serve as mRNA
polio is one example
AKA: (+)-stranded RNA and positive-stranded and positive sense RNA
minus-stranded RNA viruses
single-stranded RNA virions that contain RNA complementary to mRNA
AKA: (-)-stranded RNA and negative-stranded and negative-sense RNA
biochemical events in replication of polio virus
1: viral RNA enters the cytoplasm of the host cell and functions first as mRNA
2: this virion mRNA is translated into a large polyprotein
3: polyproteins are cleaved into functional proteins, among them viral RNA polymerase and capsomeric proteins
4: polymerase uses the virion RNA as a template to make complementary (minus-stranded) RNA that is found only in infected cells
5: the minus-stranded RNA is the template for the synthesis of more plus-stranded RNA - this RNA serves as mRNA for more viral protein synthesis and as a template for more minus-stranded RNA - synthesis increases exponentially
6: in later stages of infection the plus-stranded RNA and capsomers assemble into virions
Baltimore classification scheme
groups viruses into families depending on their type of genome and their method of replication 7 types: dsDNA (adeno, herpes, pox) ssDNA (parvo) dsRNA (Reo) (+)ssRNA (Picorna, Toga, calci, corona, flavi) (-)ssRNA (Orthomyxo, Rhabdo, para) ssRNA-RT (retro) dsDNA-RT (hepadna)
viremia
infectious virions in the blood
incubation period
length of time (days to years) between infection and the onset of specific symptoms
three general patterns of pathogenesis
1: virus grows in cells at site of entry into body but causes no significant illness
incubation period measured in weeks or months
immunity from infection of the immunity produced by an effective vaccine will reliably prevent disease and will often last for decades or life
2: virus growth in cells at site of entry into body causes illness
incubation period days
immunity dependent on secreted IgA
immunity from infection or produced by vaccines less effective and may only be short term (3-10 years)
3: virus growth in cells at site of virus entry causes no significant illness
virus spreads to other tissues by a neural pathway
longer incubation period
acute infection
infection occurs then virus is cleared
persistent infection
infection occurs and virus or virus infection is not cleared
variations = latent infection and slow virus infections
symptomatic infection
clinical symptoms of infection occur
asymptomatic infection
infection occurs but defining clinical symptoms don’t develop
aka subclinical infection, inapparent infection, silent infection
