Viral Pathogenesis Flashcards by Jason Hsu

3 ways for viruses to be maintained in nature?

shed into environment
vector: insect, needle
congenitally

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a systemic viral infection is worse than a local ? T/F?

False. Not correlated with severity

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Explain tropism

anatomical localization of infection (initially determined by receptor specificity

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What’s parenteral inoculation?

via mosquito or bite

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What determines initial site of virus deposition in the airways? Explain

droplet size.
>10um= nose
5-10um = airways
<5um = alveoli

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What the body temp in nose vs. lung bases?

33 degrees nose

37 degrees lung bases

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Rhinovirus spreads from initial site?

Nope. localised

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3 viruses that spread from infection site?

MMR baby. and varicella

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3 viruses that stay localised?

rhino
influenza
resp syncytial virus (RSV)

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What kind of cytopathic effect could RSV have on lungs?

presence of giant cells

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How does measles infect you?

breath it in
replicate in epithelials of URT
infects Macros, lymphos, DCs into lymphnodes
circulate and amplify and go back to lungs and mouth

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How are HIV and measles similar?

both cause immunosuppression

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What are koplick spots?

measles initial replication causes aggregations of lymphocytes

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T/F? Viruses that infect GI have an envelope for more protection?

FALSE YO! are acid and bile resistant, no envelope

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What does rotavirus cause?

diarrhea

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two viruses that infect GI but spread

Hep A

polio

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HIV and Hep B don’t have receptors for epithelial cells, how would they enter?

abrasions/breach via rectal route

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What’s an M cell?

kinda like a DC cell but in the GI, they’re the sentinels in the GI sampling and presenting to underlying lyphoid tissue

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how many shells does rotavirus have? why?

triple shelled to withstand the GI environment

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What does rotavirus do to you?

infects GI, destroys M cells, epithelial cells, inflammation, gastroenteritis

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Rota virus causes diarrhea, how is it amplified or dangerous to children?

dehydration

NSP4 protein increases fluid secretion

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What’s the difference between primary and secondary viremia?

primary: in circulation amplifying
secondary: reaches target tissues

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Name a systemic virus that infects meninges

enteroviruses

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Name a systemic virus that infects CNS

polio

coxsackie

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Name a systemic virus that infects skin

group A coxsackie (hand/foot/mouth) | echovirus

Name a systemic virus that infects muscle

Group B coxsackieviruses

What virus enters transcutaneously?

papillomavirus | HepB,C,HIV

What viruses from insect/animal bites?

dengue virus - fever, rash, poly arthritis

conjunctiva route is rare, what viruses can enter this way?

adenovirus enterovirus 70 HSV

What's the mechnism of spread of a virus?

``` epithelium lymph capillary vein lymph node circulation ```

in primary viremia, where is the virus

free in plasma

in secondary viremia, it infects vascular endothelium or release in large amount from what two organs?

liver | spleen

How is viremia managed by the immune system? how long?

macrophages to the rescue! take 1-2 weeks

What is cell-associated viremia?

spread via the immune system HIV - CD4 measles/dengue: monocytes

what does smallpox do to a fetus?

it's cytocidal, death and abortion

what do non cytocidal viruses do to foetuses? 2 examples?

developmental abnormalities: rubella, cytomegalovirus

what can infect a baby in the birth canal? 4 things:

herpes simplex, varicella, CMV | coxsackie B from faeces

What does congenital rubella syndrome do?

slows down cell division

4 consequences of congenital rubella syndrome?

1. microcephaly 2. heart defects 3. cataracts 4. deafness

How does polarized release determine tropism of viruses?

those viruses that prefer apical release are less likely to infect deep layers

What virus needs tryptase from Clara cells?

influenza

what is a cytocidal virus? 2 examples

death from direct viral replication 1. rotavirus 2. poliovirus

what can rhinovirus do to lungs in terms of affecting their function?

cilial stasis can predispose to second bacterial infection

What is immunopathology in terms of viruses?

immune system collateral damage

2 kinds of antibody mediated pathology:

1. Ab-dependent enhancement of infection | 2. antigen-Ab complexes

What is Ab-dependent enhancement of infection? example?

Dengue hemorrhagic, infects macrophages

What is antigen-Ab complexes? how is it bad?

big ass complexes deposit in kidney causing glomerulonephritis/vasculitis

what can cause antigen-Ab complexes?

Hep. B

Measles rash is cause by what mediated pathology?

CD4 T-cell-mediated responses

CD4 T-cell-mediated responses for viral immunopathology. What happens?

Cytokines and eosinophils recruitment can cause bronchiolitis in infants with RSV

What is RSV?

respiratory syncytial virus

What virus causes CD8 T-cell mediated responses?

Hep B.

HepB does what in terms of CD8 T-cell mediated response?

hepatocyte lysis

What are signs of liver damage in hep B?

yellow eyes, skin

How does the eyes and skin turn yellow in liver damage with Hep B?

excess bilirubin in tissues as it's not secreted into bile from old heme

Can viruses cause autoimmunity? how?

yes via molecular mimicry

2 examples of a virus mediated autoimmunity?

Guillain-Barre syndrome for nerves | coxsackie B4 for heart muscle

What Interleukin does measles suppress?

IL-12

What does Type 1 IFN a/B mainly target? what does it activate?

target dsRNA viruses | NK cells

What does Type 2 IFN-y come from? what does it do?

made by NK cells enhance MHC class I and II activated Macros

How would a virus evade T or B-cells? examples?

Latency HSV in T-cells EBV in B-cells

How would a virus evade antibodies? examples?

antigenic drift like flu and HIV

How would a virus evade T-cell recognition? 3 things

``` antigenic variation inhibit viral peptide presentation decrease MHC class I (HIV, RSV, adeno) ```

How does viral antigenic drift happen?

spontaneously through RNA errors

How would HIV evade CD8 recognition?

induces endocytosis of MHC class I and mess with the CTL epitope

What viral protein binds to cytosolic side of TAP transporter to evade CD8?

HSV (herpes simplex)

What viral protein binds to luminal side of TAP transporter to evade CD8?

CMV

What is TAP?

transporter of antigen and peptides

What does adenovirus do to MHC peptide complex?

anchors in the ER so it can't do diddly squat

what virus inhibits proteosomes?

EBV

Is NK cell a B-cell? or a T-cell?

Neither, own distinct lineage

NK cells are a major source of what?

IFN-y

What cytokines activated NK cells?

IL-12 | IFNa/b

I'm getting a lot of varicella and CMV infections... what's up doc?

you might have a NK cell deficiency

NK cells are part of innate or adaptive immune system?

innate

Do NK cells need an antigen to activate?

Nope, could be stress protein or heat shock proteins too

How many signals do NK cells need to kill?

Two 1. first is the check 2. 2nd is the inhibitory (without it, it will kill)

NK cell inhibitory receptor binds to what?

MHC class I of target cell

What happens to viruses that cause reduction of MHC class I expression?

evade CD8 but more susceptible to NK killing

What virus encodes an MHC class I-like molecule to avoid NK cell killing?

Human CMV cytomegalovirus

What is PKR? how is it activated?

activated by IFN, helps to inhibit translation of viral proteins

What does PKR need to be activated? 2 things

``` viral dsRNA (long enough) autophosphorylation ```

what is a viral evasion technique to get around IFN and PKR? which viruses?

abundant small bits of RNA that bind to PKR but not lengthy enough to activate PKR EBV/adenovirus

What does vaccinia and reovirus do to avoid PKR activation?

Virus proteins bind to dsRNA to prevent PKR activation

What competes with PKR for eIF2a activation to stop viral translation of proteins?

Vaccinia

If you are resistant to HIV, what could be causing it?

You may be missing the CCR5 secondary binding receptor

What Ig class are viruses susceptible to?

IgA

4 kinds of genetic factors influencing susceptibility to viral infections?

inherited defects (no Ig class) MHC polymorphisms interferon-inducible genes receptor genes

4 kinds of non-genetic factors influencing susceptibility to viral infections?

Age malnutrition preg/hormones/males dul infections

4 outcomes of viral infections

fatal full recovery recovery but permanent damage persistent infection