Infectious disease and pathogenicity 2- Viruses Flashcards
Structure of a virus
Nucleic acid- can be DNA/RNA single/double stranded Surrounding protein coat- capsid Icosahedral (20 sides) Helical Nucleocapsid Matrix
What is a retrovirus?
Store their genetic info as RNA instead of DNA
So when they enter human RNA must be converted to DNA to replicate
e.g HIV
What’s a nucleocapsid?
Viral capsid protein enclosing a nucleic acid
Found in the cytoplasm
Involved in viral replication
What is gp120?
Docking glycoprotein in membrane of virus
What is gp41
Transmembrane glycoprotein in virus membrane
What are glycoproteins in virus’ membranes role?
Attach virus to Host cell= fusion between membranes
Examples of non-enveloped DNA viruses
Parvovirus
Papovavirus
Adenovirus
What DNA does parvovirus have?
ss DNA
What DNA does papovavirus have?
ds DNA
Examples of enveloped DNA viruses?
Poxvirus
Herpesvirus
What kind of DNA does poxvirus have?
ds DNA
What kind of DNA does herpesvirus have?
ds DNA
Examples of enveloped RNA viruses
Togavirus
Coronavirus
Retrovirus
(all ss RNA)
Examples of non enveloped RNA viruses
Picornavirus (ss RNA)
Reovirus (ds RNA)
What is a bacteriophage?
DNA virus that infects bacteria
Have a role in bacterial virulence- spread pathogenicity to infect next bacterium
What is phage therapy?
When bacteriophages are used to kill bacteria
Used to study viral replications
But means more bacteriophage production= transmit genes to bacteria (e.g resistant)
What is viral pathogenesis?
Process where a viral infection causes disease
Outcome of infection depends on host’s response
Most infections are subclinical- don’t show symptoms
What is an acute infection?
Full recovery of infection but causes long term problems e.g acute viral encephalitis (brain swelling) leading to neurological sequelae
Can lead to chronic infection
What is a chronic infection?
Silent subclinical infection for life
A long silent period before disease appears
Can be reactivation of acute disease
Causes chronic relapse and exacerbations
Examples of viruses that have a long silent period?
HIV
SSPE
Examples of viral infections with relapses and exacerbations
HBV
HCV
What are the factors of viral pathogenesis?
Effects of viral infection on cells (intracellular pathogenesis)
Entry into host
Courses of infection (primary rep, systemic spread, secondary rep)
Cell/tissue tropism
Cell/tissue damage
Host immune response
Virus clearance/persistence
What is cell/tissue tropism?
cells and tissue of host supporting growth of a virus/bacteria
What are the 3 ways that cells can respond to infection?
- No change
- Death
- Transformation
How does virus cause direct cell damage/death?
- Division of cell’s energy= apoptosis
- Inhibiting macromolecular synthesis
- Ribosomes in cell competing for viral mRNA
- Competition for viral promoters and transcriptional enhancers e.g for RNA polymerases
- Inhibit interferon defence mechanisms
How does a virus cause indirect cell damage?
Viral genome is integrated
Mutations in host genome
Inflammation
Host immune response
What routes can virus’ take to enter body?
Skin- cutsabrasions, virus can employ vectors to breach skin barrier Conjunctiva and mucous membranes GI tract Respiratory tract Urogenital tract
Process of viral replication?
- Virus penetrates host cell
- DNA/RNA released from virus (uncoating)
- Viral DNA is integrated by integrase
- RNA converted to DNA (if needed)
- Viral subunits are synthesised- protease acts on polypeptides
- Virus is assembled
- Lysis of cell= virus spreads and infects nearby cells
What is primary replication?
Place where virus replicates after initial entry into host cell
determines if infection will stay localised or spread= systemic infection
What is systemic spread?
Virus can spread via bloodstream/CNS
What is secondary replication?
Result of systemic spread
New area that is infected
Cell tropism- what is the viral affinity for body tissues determined by?
Cell receptors for virus
Cell’s TF’s that recognise viral promoters and enhancer sequences
Cell’s ability to support viral replication
Physical barriers
Temperature, pH, oxygen
Digestive enzymes and bile in GI tract that may kill viruses
What is different about retroviruses?
Tend not to kill cells
released from cell by budding rather than lysis
Cause persistent infections
What does picornavirus cause?
Cause lysis and death of host cell
leading to fever and increased mucus
What has the greatest impact on outcome of infection?
Immune response
Role of cellular and humoral immunity in clearing the virus
Cellular immunity- clears virus
Humoral immunity- protects against reinfection
What is the result when a virus stays and isn’t cleared from the body?
(Chronic) persistent infections
What are the 2 types of persistent infections?
A chronic infection is a type of persistent infection- is eventually cleared, while latent or slow infections last the life of the host
True latency - latent viral infection- When a virus is present in the body but exists in a resting (latent) state without producing more virus. A latent viral infection usually does not cause any noticeable symptoms and can last a long period of time before becoming active and causing symptoms
What is true latency?
Virus remains in cell for a long time
Genome still integrated in host’s genome or exist as episomes (DNA replicates independent of host)
Example of a true latent virus
HSV (herpes simplex virus)
VZV (varicella-zoster virus)
What is persistence?
Virus not completely removed
replicates at a very low level- interferons control low levels
Examples of a virus that persists?
HIV
HBV
Mechanisms of viral persistence?
Antigenic variation- strains of virus change so new antibodies needed
Downregulation of MHC I expression- lack of immune cells recognising virally infected cells
Down-regulation of accessory molecules in immune response e.g LFA and ICAM
Infection of immunoprivileged sites in body e.g HSV in sensory ganglia of CNS
Direct infection of cells in immune system= immunosuppression
What viruses directly infect cells of the immune system?
Herpes virus
HIV
Clinical features of hepatitis B
Long incubation period
Replicates at low levels before clinical problem arrives
Result of damage to liver= jaundice
Spectrum of hepatitis diseases
chronic persistent hepatitis- asymptomatic
chronic active hepatitis- symptomatic exacerbations of hepatitis
Cirrhosis of liver
Hepatocellular carcinoma (liver cancer)
Treatment of hepatitis B
Cure- pegylated interferon with a nucleotide analogue
reduces viral replication- targets viral RNA polymerase
Problem with treatment for hepatitis
Treatment is expensive- lifetime regime
virus can be resistant
What are orthomyxoviruses (influenza)
Enveloped ss RNA (10 genes encoded on 8 separate RNA segments) 3 types of influenza- A,B,C
Which type of influenza causes the most infection?
A
What is the tropism that influenza uses?
Respiratory tract
What is in the lipid bilayer of orthomyxoviruses (influenza)?
Haemagglutinin and neuraminidase glycoproteins
Hemagglutinin spikes on viral membrane attach to respiratory tract= agglutination of RBCs
Orthomyxovirus life cycle
- Virus’ hemagglutinin spikes attach to respiratory epithelial cell and fuses with membrane
- Virus is endocytosed- in a vesicle
- Virus is uncoated= nucleocapsid segments released into cytoplasm
- Nucleocapsid segments transported to nucleus
- sense RNA strand converted to + sense strand
- +sense RNA strand used in transcription and translation to make viral proteins- capsid, glycoprotein spikes in virus membrane
- sense RNA strand makes new - RNA strands- assembled into nucleocapsids and released from nucleus to cell membrane
- Mature virus is released an budded off with an envelope and spikes
What is the latency period?
The time between being infected and becoming infectious
What is the incubation period?
Time from being infected to showing symptoms (infectiousness)
Differences between a cold and flu
Fever: cold= rare, flu= prominent
Headache- cold= rare, flu= prominent
Extreme exhaustion- cold= never, flu= prominent
Sore throat- cold= common, sometimes
What are hemagglutinin glycoprotein spikes found on influenza?
15 different subtypes
most important virulence factor
attaches to host cells
What’s neuraminidase found in membrane of influenza?
9 different subtypes
assists in viral budding and release
What do the glycoproteins- neuraminidase and hemagglutinin frequently undergo?
Genetic changes (mutations) = reduce effectiveness of host immune response
What is antigenic drift?
Constant mutation (year on year) simple point mutation
What is antigenic shift?
1 of genes/RNA strands swapped with gene/strand from another influenza virus from a different animal host
Results in new HA and/or new HA and NA proteins in influenza viruses that infect humans
Characteristics of influenza A
Acute, highly contagious respiratory illness
Respiratory transmission
Binds to ciliated cells of respiratory mucosa
Causes shedding of cells in respiratory epithelium= severe inflammation
Symptoms of being infected by influenza A
Fever headache myalgia pharyngeal pain shortness of breath coughing
What is a secondary infection that can result from influenza A?
Pneumonia
Diagnosis of influenza A?
Rapid immunofluorescence tests- detect antigens from pharyngeal specimen
serological testing- blood test that looks for antibodies in blood
Treatment for influenza A
Oseltamivir
Zanamivir
Amantadine
Rimantadine
Prevention of influenza A
Vaccine
Acyclovir MOA etc
Anti-viral
Interaction: viral DNA polymerase
MOA: Inhibits viral DNA polymerase
- Converted into acyclovir triphosphate- higher affinity for viral DNA polymerase than cellular NDA polymerase
Competing w DNA polymerase so strongly preventing other bases associating with the enzyme
Preventing DNA replication
