19. Patterns of Viral Infection Flashcards
What are viruses?
obligate intracellular pathogens
packets of genetic information that can reprogram the host cells
what do the different viral genomes infer?
different intracellular lifestyles
what is the problem with different viral lifestyles?
makes it hard to develop broad spectrum treatments
how do viruses trigger the immune response?
viral particles being detected
viral proteins on the cell surface being detected
What is the progress of viral infection?
establish infection
regulation of gene expression
antigenic variation
immune invasion
immune subversion
What are the basic requirements for viral infection?
enough virus present to initiate infection
cells at the site of infection must be susceptible to the virus
local antiviral defences must be absent or ineffective
what causes viral tissue tropism?
Susceptibility of cells at site of infection
what are innate defences to viruses?
type 1 interferons inducing the transcription of antiviral genes
lysis of infected cells by NK cells triggered by changes in the cell surface
what antibodies are useful in viral infection?
IgG
IgM
IgA
What antibody function is the most effective against viruses?
neutralisation
What is neutralisation?
antibodies binding to viral particles and blocking their receptors
Does opsonisation occur in the antiviral response?
yes but less likely to occur then neutralisation
What is antibody dependant cell-mediated cytotoxicity?
Antibodies bind to viral receptors and Fc receptors on NK cells.
NK cells release cytotoxic granules to kill the virus
What kind of adaptive defences are more important in viral defence?
cell-mediated immunity
what are the 2 cells involved in viral cell mediated defences?
CD8+ T cells
NK cells
What is the role of CD8+ T cells in viral cell mediated defence?
MHC restricted killing
Recognise infected cells
HLA process and present the antigenic peptide
kill the cells that they recognise
provide long term response
What is the role of NK cells in viral cell mediated defence?
Non- restricted killing
kill any cells that trigger PRR
What is the role of ADCC in viral cell mediated defence?
antibody binds to a viral protein and helps cytotoxic cells recognise them by binding to Fc receptors
How can viruses evade host defences?
genetic reassortent to change the structure of surface receptors (dramatic changs can make new strains)
stealth - low levels of infection so don’t generate an immune response
disruptions - killing immune cells like HIV
non-cytopathic infections
what are the 4 different type of virus infection?
Acute - eg smallpox
persistent - eg hep B
latent - eg herpes
slow - eg HIV
what is the difference between a persistent and latent infection?
persistent - can be asymptomatic but still transmissible
latent - only transmissible when infections are active
what is the course as a typical acute infection?
initially innate defence while the virus is at lower levels
stimulate the adaptive immunity as the infect reaches its peak
adaptive immunity is responsible for clearing infection
what are the main defences against acute viral infection?
innate - interferon response and NK cells
Adaptive - final clearance of virus, provides memory
what may happen in an immunocompromised host?
the infection may not stay local to the primary infection site
what are the general symptoms of viral infection resulting from immune response?
fever
malaise
aches
nausea
how can viruses cause direct cell damage?
cell lysis
toxic viral proteins
cell killing by the immune system
what are the symptoms of viral infection resulting from cellular damage?
depends of virus:
diarrhoea
poor lung function
poor liver funciton
breakdown of capillary beds
what are clinically inapparent acute infections?
successful infections with no symptoms
still active virus infection cycle
infection rapidly controlled by immune system
usually well adapted pathogens
what are multiple acute infections?
initial infection followed by 2nd or 3rd round of infection
could be 2nd acute infection
Acute infection example = human poliomyelitis
typically mild intestinal infection with no symptoms
can enter the bloodstream (usually in immunocompromised)
can enter multiple different tissues
enter CNS = paralysis and death
why are acute viral infection important public health matters?
often associated with serious epidemics
difficult to treat or detect before transmission
preventative measures often too late
What are the characteristics of persistent viral infections?
virus particles/products are produced for long periods
virus could be produced intermittently or after long periods of latency
persistent infections can eventually be cleared
latent and slow infections will last the life of the host
What is integral to persistent infections?
virus adjusting its replication and pathogenicity
evastion of host immunity
How do persistent viruses AVOID the host immune system?
Infection of immune privileged sites (no active immune Surveillance) eg skin, eye, brain, CNS
down regulation of viral gene expression
viral protein structure limits antigenicity
high frequency variation of antigenic epitopes
How do persistent viruses INHIBIT the host immune system?
subvert the immune system
- inhibit MHC1 and MHC2
- inhibit NK cell lysis
- interfere with apoptosis
- inhibit cytokines like interferons
produce host mimicking compounds
direct infection of immune cells like HIV
what are the 4 characteristic properties of latent infections?
- infect a non replicating cell or the viral and host DNA is replicated together as not to disrupt the cell
- immune detection of infected cell is reduced/eliminated
- expression of viral genes for making virions is absent
- the viral genome persist and is capable to starting an acute infection later
an example of a latent infection
Herpes simplex 1
primary infection = cold sores, fever
latent infection = asymptomatic with no virus production, viral DNA resides in trigeminal nerve ganglion
reactivation = virus replicated and travels down sensory nerse to infect epithelial cells
what is the main feature of slow viral infections?
many years pass between the initial contact with infectious agent and fatal disease
difficult to study due to long duration
what are some unconventional slow diseases?
prions - transmissable spongiform encephalopathies
an example of a slow infection
measles virus - normally acute but can switch to persistent subacute sclerosing panencephalitis
appears 7-10 years after infection and effects 1 in 1 million cases
causes progressive neurological deterioration and death
defective measles virus can be detected
