L16 - Virus Pathogenesis Flashcards
What are the diff factors of epidemiology?
Mode of transmission, age, gender, ethnic packground, travel history, occupation, season, underlying medical conditions
Describe the 2 different routes of transmission and give examples of each
Horizontal transmission
- direct contact (secretions, blood) - HIV
- respiratory - influenza/SARS CoV2
- contaminated inanimate objects (SARs, EBV)
- faecal/oral (polio)
- insect vector (dengue)
- zoonoses (ebola)
Vertical transmission
- mother to fetus (rubella, HIV)
What are some characteristics of transmission?
- with or without disease symptoms
- during asymptomatic shedding of virus
- during incubation period (before symptoms)
What is primary infection and why is it harder to contain
- when person is first infected it can produce disease or no reaction and asymptomatic. It can get reactivated (secondary disease)
What is an example of secondary disease being reactivated?
VSV causes chicken pox as primary infection and shingles when reactivated
Describe the host organism relationship and what it is influenced by.
Influenced by:
- host’s primary physical barriers
- host’s immunologic ability to control and eliminate and invading organism
- organism’s ability to evade destruction (immune evasion)
- pathogen virulence factors
- ability of organisms to spread in the body
What is the cycle of virus infection?
Entry
Primary site of replication
Spread within host
Secondary site of replication
Shedding
Transmission
What is the patterns of disease and effects on cells
- Pathology/symptoms
- Cytopathic effect (cpe)
How does virus enter the body
Through mucous membranes or skin
- respiratory tract
- oral
- sexual
- ocular
- percutaneous (needles, wounds, bites)
Describe the difference between primary and secondary sites
- primary = virus largely replicates, shedding of virus to infect new host to get transmitted
- spreads systemically (lymph nodes/brain/ access to blood) → replication to secondary site (shedding)
Describe the course of infection of mouse pox
- mousepox infecting mice
- it spreads between mice when they fight through skin injury (skin blisters)
- similar to smallpox but is through respiratory tract instead of skin
- regional lymph node multiplication
- enters bloodstream (primary viremia) → detectable
- enters spleen and liver → further multiplication of virus (necrosis)
- enters blood (Secondary viemia)
- travels to skin (focal infection multiplication)
Course of infection can be split into one of 3 outcomes. What are they?
- acute infection - progress rapidly, peaks and transmission, immune system kicks in and eradicates virus (days or weeks at most)
- chronic infection - aren’t eliminated by immune system (maybe through mutation), persists through the host and continues replicating. replication peaks but continues to get transmitted and stays in the host
- latent infection - primary course of infection → shedding → seems to eliminate but it becomes dormant and stable through the lifetime of the host and is able to come back
Give examples of acute, chronic and latent infections
Acute = influenza
Chronic = hepatitis B
Latent = cold sores
What are viruses effects on cells?
abortive infection : blocks virus replication through restriction factors
cpe - caused by processes that virus initiates in cells. switches off translation of host cell mRNA, host cell protein production is limited such that the cells concentrate on production of virus proteins instead of cellular protein.
apoptosis = cell death, not good for virus so they avoid or actively block these pathways so the host cell doesn’t die
some virus can transform the cell → tumour development
PRRs → recognised by innate immune response and activates interferons and cytokines
What is the Cytopathic effect cpe
Syncytia = cells merge together to become multinucleated holes/plaques
Virus infection often switches off ______ . How is it proven experimentally?
Host cell protein synthesis
- unaffected = lots of protein
- as time proceeds and cells are infected with virus = less cellular proteins but lots of production of virus protein
How is the host protein translation shut off by poliovirus?
- cleavage of cap binding complex (involved in binding the m7G cap structure at th3 5’ end of all eukaryotic mRNAs during initiation of translation)
- 2A (poliovirus) destroys CBC and binds to cap structure of 5’ end of eukaryotic mRNA
- overcomes need to 5’ m7G cap because virus contains IRES (internal ribosome entry site)
- ribosomes will translate virus mRNA until virus> host RNA
How is the host protein translation shut off by influenza virus ?
- steals cap from the end of mRNA and some of the sequence and uses it as a primer for production of its own mRNA
- chimeric viral mRNA → code transcribed
- host RNA destroyed and lots of viral mRNA
What is apoptosis and what is the mechanism?
programmed cell death initiated by complex pathway
- activation of proteins
- leads to breakdown of DNA and cell
- apoptopic bodies taken up by phagocytes and antigens are sampled, any foreign antigens will be presented to initiate immune response
Transforming viruses : cells to tumours
HPV
Retroviruses
Herpesviruses
Hepatitis B/C
HPV - cervical carcinogen, head & neck cancer
Retroviruses - HTLV1, adult T cell leukemia
Herpesviruses - EBV, KSHV
Hepatitis B/C - hepatocellular carcinoma
Describe characteristics of HPVs
- > 160 named types, non-enveloped, DNA genome
- ubiquitous, infections can be asymptomatic/commensal
- but some cause benign skin warts (papillomas)
- other cause cancer of uterine ceervix or epithelial cancers
How does HPV lead to cell cycle disruption -> tumour
E6 and E7 genes of HPVs mediate destruction of tumour-suppressor proteins p53 and pRB respectively. No control of cell cycle progresión so tumour development
What is the HPV vacccine?
- recombinant virus like particles based on HPV capsid protein L1
- elicits HPV neutralisingh antibody responses that protects against primary infection
- quadravalent vaccine protects against HPV 16,18,6,11
- nonvalent vaccine protects against HPV 31/33/45/52/58
How does TLR (PRRs) recognise and respond to viral infections? What about other aspects of the innate immune system?
• PRRs recognize viral proteins or nucleic acids (genome products).
• Cytoplasmic sensors also detect viral components.
• Detection triggers proinflammatory cytokines and interferons, initiating the innate immune response.
What are interferons? What is the one that plays a major role in activating the adaptive immune response?
Small molecules produced in response to virus that plays a major role in inhibiting virus infection in cells. Type 2 plays a major role in activating adaptive immune responses
What is a cytokine storm?
cytokine storm - normal process of pro inflammatory cytokines and interferons ends up in a loop of those cytokines, release of more proteins leading to further activation of these activation.
- overactivation and stimulation which leads to severe effects
What are immune modulation strategies used by viruses?
- secreted modulators (cytokine/chemokine mimics and binders (pox, herpes)
- modulators on infected cell surface (mimics immune signalling)
- stealth/latency (express few/no proteins (herpes)
- antigenic hypervariability (flu, HIV, HCV)
- block adaptive immmune response, inhibit complement, interfere w PRRs, block interferon/proinflammatory cytokines
