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IMIN 200 > Final Exam > Flashcards

Final Exam Flashcards

1
Q

T or F. We start life in a sterile womb environment

A

T! All our bacteria come from environment; initial colonization is at birth

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2
Q

Colonization

A
  • establishment of microbial flora starts at birth (flora changes as we age)
  • begins at birth
  • sources: vaginal birth canal
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3
Q

Gut microflora differs depending on country of birth

A
  • Developing world in a rough swath = more E. coli as primary colonizers
  • Developed world = lactobacilli and Lactococcus are primary colonizers
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4
Q

Purposes of normal flora

A
  • protection from pathogens (competitive exclusion)
  • required for developmental processes (involved in development of gut by modulating gene expression)
  • provide vitamins and nutrients (E. coli = vit K and 90% of our serotonin is bacterially produced ; can also digest certain fibers and lactose)
  • aids in digestion (trains immune system (NTBF) to distinguish b/w flora and pathogens and you! (SELF))
  • modulates the immune system
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5
Q

NTBF excluding its cousin, ETBF

A

NTBF produces a perforin-like toxin (T6SS - bacterial warfare) to kill its cousin (ETBF)
- Perforin-like toxin is a TLR2 agonist and it suppresses immune system
=> suppresses immune system against particularly good bacteria and so the agonist is encouraged to say don’t attack me .. Im normal.. Don’t recognise other good bacteria as normal
- ETBF = associated/not causative with increased risk of colitis (disruption in ability to absorb nutrients in large intestine = malnourishment, diarrhea), if see decrease in NTBF then flourishing of ETBF and increase risk of colitis and so they think that ppl prone to colitis will be due to antibiotic use

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6
Q

C. diff

A
  • pseudomembranous colitis
  • most frequent cause of infectious diarrhea in hospitals and LTC facilities in Canada
  • lots of antibiotic resistance now
  • Gram + spore former
  • 3 toxins = TcdA, TcdB, and CDT
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7
Q

C. diff’s Tcd’s toxins

A

Tcd’s are glucosyl transferases = inactivate G protein that signal tissue integrity = loss of junctions b/w epithelial cells = leakage! => Rho and Rak GTPases inactivated through glycosylation activity

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8
Q

C. diff’s CDT toxin

A
  • dimer and is a binary toxin
  • acts as a ribosyl transferase = transferring a ribose
  • modifies microtubule (MT) cytoskeleton to facilitate microvilli extension and pathogen invasion
  • fuzzy villi = unable to absorb nutrients and more area for pathogen adhesion/invasion
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9
Q

T or F. Bacteria in gut produce 90% of feel good neurotransmitter

A

T!

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10
Q

Hygiene hypothesis

A

Exposure to normal flora keep immune system on idle; excessive hygiene can lead to not training your immune system to not be able to distinguish between what’s bad/good => hyperactive immune system => autoimmune disease

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11
Q

Fibre

A

Fibre feeds good microbes (fibre fermented by microbes in gut to butyrate - regulates reg T cells which prevents autoimmune rxns)

  • sugar feeds bad microbe
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12
Q

MS

A
  • Multiple sclerosis - common in AB; attack on myelin sheath
  • rare disease in areas with a high helminth burden
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13
Q

Helminths for MS?

A

If expose patients w MS to helminths => symptoms improve .. Now have helminth infection but better than MS?

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14
Q

Probiotics

A

live bacteria that are consumed ; yogurts, kimchi, sauerkraut

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15
Q

Do probiotics work?

A

Probably not that well! Depends on who you are ..

Won’ t hurt if you just were on antibiotics, diarrhea, etc.

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16
Q

Prebiotics

A

food for bacteria; they work!!!

- any fiber = but esp inulin fiber - onions, leeks, garlic, seaweed, cabbage, kimchi

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17
Q

Pandemic

A

worldwide epidemic

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18
Q

Biggest virus

A
  • Pox virus
  • 1/3 size of bacterium
  • one of the first tests = filter; if can pass through 0.45 micrometers - unlikely to be bacteria
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19
Q

T or F. DNA viruses have a lower mutation rate than RNA viruses

A

T

- RNA virus (coronavirus) can mutate and the smaller the virus, the less likely it has the ability to correct mutations

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20
Q

The _______ the virus the less likely that it uses its ______ to encode things that can correct mistakes

A

smaller; genome

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21
Q

What does a virus need?

A
  • to be able to enter a host cell
  • have the host cell replicate the viral genetic material
  • have the host cell transcribe and translate the viral genes

-> once all the virus components are made, the infectious viral particle (VIRION) can be assembled

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22
Q

Case fatality rate of yellow fever

A

~20%

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23
Q

River’s Postulates

A
  • modified Koch’s postulates
    1. isolation of virus from diseased hosts
    2. cultivation of virus in host cells
    3. proof of filterability (confirms small size)
    4. production of a comparable disease when used to infect experimental animals (host animal or related)
    5. re-isolation of the same virus from the infected host
    6. detection of a specific immune response to the virus
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24
Q

All viruses follow a general strategy: (3)

A
  • package their genomes inside a particle that mediates transmission from host to host
  • virus genome contains the info for an infectious cycle within a susceptible permissive cell (for some viruses = only nucleic acid is necessary)
  • all viruses are able to establish themselves in a host population so that their survival is ensured
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25
Q

Glycoproteins of viruses

A

necessary for viral entry

- corona surrounded by crown of these (stuck in membrane of virus)

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26
Q

All enveloped viruses have to remain ___ to be viable

A

wet!

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27
Q

Viral capsid

A
  • protects genetic material
  • resistant to proteases, heat, or temperature extremes
  • ## uses as few proteins as possible
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28
Q

T or F. Enveloped viruses are much more susceptible to the environment

A

T
Viruses that don’t have a membrane like norovirus = just has protein coat = incredibly difficult to remove from an environment bc they are so resistant and remain infectious even when they dry out

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29
Q

Arrangement of nucleic acid and protein coat in tobacco mosaic virus

A
  • the RNA assumes a helical configuration surrounded by the protein capsid
  • the information for assembly is contained within the protein structure itself
  • process called self-assembly

**how does the virus know how to assemble? = structure of protein defines RNA binding

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30
Q

Simplest/smallest virus

A
  • has protein coat
  • proteins assume shape as soon as they’re made
  • 60 copies of each of 4 proteins (VP1-4)
  • assembly uses as few proteins as possible = easier synthesis
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31
Q

Simplified viral life cycle

A
  • Attachment: viruses use a variety of receptors
  • Penetration: crossing the membrane
  • Utilization: host cell proteins/enzymes needed for replication, transcription and translation
  • Biosynthesis: synthesis of proteins
  • Assembly: progeny particles are produced
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32
Q

‘Life’ cycle of an enveloped RNA virus (measles or CoV)

A
  • the viral envelope membrane fuses with the host cell membrane to allow entry
  • RNA is transcribed and replicated using viral enzymes
  • virus can leave cell by budding off, taking some host cell membrane with it
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33
Q

Viruses replicate _____________

A

exponentially
- take over host cells and in 24 h make 50 000 copies of itself and release viral particles by rupturing cell; de novo synthesis of viruses = massive!!!

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34
Q

Viremia

A

active replication of virus in some cells = HIV = will have infection for a long time

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35
Q

How is the viral titre determined?

A
  • a dilution is mixed with bacteria and melted agar
  • poured onto agar plate
  • phage plaques make ‘holes in lawn’

**hard to talk about cocntn of virus bc can’t count by seeing them so use plaque assay using bacteriophage – series of dilution of phage, molten assay and melted agar …
**top agar = phage (temp, that doesn’t kill either bacteria and phage) ; phage infects bacteria but semi-solid so can’t release contents in environment; can only infect neighbouring cells
=> holes in bacterial wall

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36
Q

Viral classification is based on

A

the nature of the genetic material (ss/ds DNA/RNA?), symmetry of capsid, presence of an envelope, dimensions

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37
Q

RNA viruses

A 
polio
HIV
CoV
influenza
measles
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38
Q

DNA viruses

A

Herpes, pox virus

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39
Q

Initiating a viral infection:

A
  1. sufficient virus at site of entry
  2. host cells must be susceptible
    - susceptible cells have receptors required for viral entry
    - host cells are permissive (factors needed for replication and dissemination)
  3. local antiviral defense must be breached
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40
Q

The 1918 pandemic killed 40 million people worldwide

A

influenza

  • acute infection; aerosolized sneeze = lots of virus in those droplets! Same for cough!!! will remain in air for a long time esp longer if smaller
  • killed 1/5 of world’s population
  • most deadly to young people - very good immune responses
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41
Q

Course of an acute infection

A

rapid and self-limiting

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42
Q

Acute viral infecitons

A
  • rhinovirus
  • rotavirus
  • influenza virus
  • coronavirus
  • poliovirus
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43
Q

Dyspnea

A

difficulty breathing

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44
Q

T or F. Old SARS more likely to remain in aerosols than new SARS

A

T; new SARS still will but shorter time

- very little evidence found that ppl have been infected through touching surfaces

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45
Q

Acute HBV

A

fever, loss of appetite, nausea, vomiting, abdominal pain, yellow colouring of the eyes, dark urine, and clay coloured or light stools

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46
Q

Chronic HBV

A

symptomatic or not, approximately 5-10% of adults and 95% of perinatally-infected infants are unable to clear the virus, thus becoming chronic carriers
- can develop (small %) chronic hepatitis, permanent liver damage or liver cancer

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47
Q

Acute vs Chronic HBV

A

depends when u get the infection!
90% of adults will clear infection (acute)
perinatal = chronic

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48
Q

If Hepatitis B is in the acute phase of an infection (rapidly replicating in liver and causing mld symptoms) what are the symptoms and how to test?

A
  • fever and loss of appetite + yellow eyes

- PCR (days for result)

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49
Q

If a person has cleared Hepatitis B and want to know if they ever had the infection, what test is used?

A

Antibodies test

*chronic = virus always present in blood

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50
Q

Herpes simplex I

A
  • can remain latent for years
  • 20% of population have recurrent symptoms
  • hides in trigeminal ganglia; reactivated when stressed
  • nerves typically protected from immune responses so virus likes to hang out there
  • when latent = not really making more copies of virus … just hanging out – when reactivated, make tons of virus then creates lesions = virus-rupturing cell and our immune response rupturing virus = cold sore
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51
Q

An extreme persistent infection

A

latent infection

  • symptoms may not always be present while virus is infection
  • virus hides from immune system
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52
Q

Chronic vs Latent

A

HPV where virus is present all the time ; not hiding! ; tons of it in the blood of chronic infected person
Where latent = virus is in hiding ; could take years between episodes before virus is reactivated; and cause lesions

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53
Q

This causes an acute infection and a rare latent disease

A

measles

  • measles outbreak in 1781 (Faroe Islands) nd again in 1846; old people were immune
  • acute typically and only once in a lifetime
  • infects humans only and we have good vaccine for it! ; could potentially eradicate!
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54
Q

Most contagious virus

A

Measles
- contagious maybe due to way it makes u cough - back of ur throat an tongue becomes a spring board that launches aerosolized particles in air

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55
Q

These viruses have a long latency period followed by an acute infection

A

slow viruses

  • may be present at tmie during latency (HIV)
  • OR undetectable for years (measles SSPE)
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56
Q

SSPE

A

measles subacute sclerosing panencephalitis
- most ppl that get measles will clear the virus, but 1 in 1000 ppl will get very rare form of measles called SSPE = measles virus remains latent ; could remain latent for 60 yrs

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57
Q

Slow virus infections

A

measles SSPE, HIV

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58
Q

Poliovirus

A
  • one of the smallest viruses
  • RNA virus
  • fecal-oral transmission (water)
  • early 1900s = caused increased outbreak ironically due to better sanitation
  • mutations to enter neurons = may replicate and lyse cells = paralysis (one or multiple or even unable to breathe) - 1%
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59
Q

Loss of contact inhibition

A

cells normally do not pile up on each other

- but cancer-transformed cells do pile up on top of one another = replicate like crazy

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60
Q

Anchorage independence

A

cancer cells lose their attachments and become mobile

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61
Q

Avian transducing retroviruses

A
  • retroviruses can take up cellular DNA; they integrate a provirus form into the genome
  • Rous sarcoma virus has taken up a src gene, called v-src to distinguish it from cellular src
  • Src is a cell signalling molecule that phosphorylates proteins involved in signal transduction
  • unregulated cell signalling from v-src causes cancer
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62
Q

T or F. The entry passage of virus cannot facilitate uncoating

A

F, they can! Virus entry is not passive!

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63
Q

T or F. Viruses can pass freely through membrane

A

F! They can’t in either direction

- many proteins on outside of cell are glycoproteins and many virus receptors are often glycoproteins

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64
Q

Uptake of viruses into cell by

A

receptor-mediated endocytosis

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65
Q

Receptor-mediated endocytosis

A
  1. ligand binds a cell surface receptor; diffuses into an invagination coated with clathrin
  2. clathrin pit pinches off forming a ‘coated vesicle’ (involves E!)
  3. clathrin uncoats vesicle
  4. the vesicle fuses with early endosome (receptor is on inside; virus gets out BEFORE fusion with lysosome)); early endosome is ACIDIC
  5. acidification releases the ligand from the receptor, and the receptor is returned to cell surface
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66
Q

These are related picornaviruses

A

rhinovirus and poliovirus

  • both use proteins on the host cell as receptors
  • receptor proteins look structurally similar (Pvr = 3; Icam-1 = 5)
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67
Q

Poliovirus receptor

A

Pvr

- involved in DC-NK interactions

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68
Q

Rhinovirus receptor

A

Icam-1 (intercellular adhesion molecule-1)

  • causes common cold; more than 90 related serotypes
  • Icam-1 involved in macrophage and T-cell interactions
  • lines respiratory tract and rhinovirus uses it for entry into cells
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69
Q

Human rhinovirus entry and uncoating

A
  • virus attaches to Icam-1 and enters by endocytosis
  • acidic environment of the endosome causes the uncoating of the particle
  • RNA is released into the cytoplasm
  • Icam-1 deep in canyon facilitates destabilization of capsid; direct interaction b/w receptor and capsid
  • rhinovirus is not resistant to acid unlike poliovirus
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70
Q

Receptor interaction site of rhinovirus is inaccessible to Abs

A

Abs bind deep into that canyon as well and blocks binding of Icam-1 = very very effective neutralization strategy = Abs excellent at preventing binding of virus to receptor and entering cell

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71
Q

Where on Icam-1 does rhinovirus bind?

A

N-terminus; D1??

- binding sites for LFA-1 (natural ligand) and human rhinovirus overlap

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72
Q

Interaction with Pv causes a major structural change

A

Formation of a pore in the membrane! This is how RNa can escape the capsid

  • N termini of the VP1 protein extends into the membrane
  • may form a pore in which the RNA can enter
  • Fc-receptor mediated internalization of poliovirus (by macrophage for ex) does not allow uncoating)
    • so when in macrophage, it can never get out of capsid bc needs interaction with Pvr to destabilize capsid) **
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73
Q

Entry of an enveloped virus

A

Enveloped viruses all have to encode their own fusogens = involved in fusing to membranes - in order for virus to get out from inside its membrane, it has to fuse with host membranes = two membranes become one part and everything inside is uncoated and becomes available for uncoating at that step

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74
Q

Cellular receptor for influenza virus attachment

A

Sialic acid (doesn’t matter which protein; carbs usually have sialic acid as terminal chain)

  • integral membrane glycoproteins are the receptors of influenza binding
  • influenza virus hemagglutinin (HA) binds to terminal sialic acid
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75
Q

T or F. Influenza is an enveloped virus

A

T!

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76
Q

Influenza virus entry using hemagglutinin fusogen

A

** virus RNA is inside two membranes; to get it out, it uses its fusogen **

  • globular head of HA bind to sialic acid on surface of cell; then particle is internalize into an endosome
  • fusogenic peptide is exposed by an acid catalyzed structural change
  • acidic environment of the endosome causes conformational change in HA ; acidification also causes the two membrane to get pulled together to become one
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77
Q

Fusogen

A

inserts deeply into membrane of host cell bc it is highly hydrophobic and can enter lipid bilayer and now held together by tail of spike proteins as well as fusogens deep into the membrane
- used by enveloped viruses so that RNA can get out

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78
Q

Hemagglutinin (HA) ias activated when cleaved into …

A 
HA1 = receptor binding domain bc its part that actually binding sialic acid; no role in membrane fusion part
HA2 = conformational changes in this expose fusogenic peptide and further structural changes in HA induce membrane fusion
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79
Q

SARS-CoV2 uses this receptor for entry

A
  • ACE2 (angiotensin converting enzyme 2)
  • essential regulator of heart function expressed in the heart, lung, kidney, and gastrointestinal tract
  • functional receptor that acts as an entry point into human lung cells for coronaviruses such as SARS and novel coronavirus
  • plays a role in human to human transmission and cross-species transmission
  • interacts with spike protein(s)
  • the coronavirus spike protein receptor-binding domain structure is similar to the SARS spike protein suggesting similar function
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80
Q

Debunking myth that the coronavirus is lab-made

A

Lots of scientists looked very carefully at the key residues that are involved in binding to the human ACE receptors

If someone were to engineer these they had to use known proteins that bind to ACE receptors
but unlike we’ve ever seen … but similar to other bat coronaviruses than anything else

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81
Q

RBD of coronavirus

A
  • receptor binding domain = RBD is lying on surface not on an active conformation
  • has to be bound/pre-activated by furin (from host; compensation for hidden RBD so affinity is still high for ACE2) to easily adopt the conformation it needs to bind human ACE2
  • lying down allows it to hide its important parts from immune response = IMMUNE EVASION
  • activated by proteases = standing up form is what engages the ACE2 receptor
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82
Q

Vast majority of transmission for HIV occurs in

A

heterosexuals (WORLD)

US - homosexual, then intravenous drug users

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83
Q

T or F. Transmission through saliva is a concern for HIV

A

F! Blood-borne virus ; stays in blood; intravenous drug injection and sharing needles = common way it gets passed and reason why w should support thing such as free needles for intravenous drug users and prison = share anything they can use to inject drugs; also through sexual contact (secretions, etc.)

**CSF heavily infected so in the late stage = neurological damage in infected individuals, but not really transmitted through CSF)

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84
Q

Seroconversion

A

Takes 2-6 weeks
The transition from infection with HIV to the detectable presence of HIV antibodies in the blood.
Most HIV tests check for the presence of HIV antibodies. So, if a person who has contracted the virus takes a test before seroconversion begins, the result will usually be negative
- sometimes there are flu-like symptoms during this stage but not all ppl with HIV ever get symptoms; some won’t know they’re infected unless they get testes

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85
Q

2-10 years of CDF T cells depletion due to HIV infection

A

2-10 yrs in an untreated indiv = continue to have viremia that they’re able to control it and they would seem fine, can’t outwardly tell they’re infected ; only when T cell count drops below 500 microL = that see symptoms = opportunistic infection that also accompany depletion of immune response like pneumocystis pneumonia

  • opportunistic infections => death bc such weak immunity
86
Q

The virion of immunodeficiency virus

A
  • the surface of HIV carries envelope glycoproteins

- each capsid carries two RNAs and reverse transcriptase (enzyme that copies RNA to DNA)

87
Q

Surface proteins of HIV are made by

A

enveloped genes: gp120 (outside) and gp41 (crosses membrane)

88
Q

Inside HIV capsid

A

two RNAs
reverse transcriptase
integrase protein
protease

** puts in capsid bc very first thing it does when enters cell is it makes its RNA into DNA and then integrates DNA right in our genome; does this before it synthesizes proteins, starts infection, etc. So can’t tell that cell is infected as this process is happening; once genome integrated into genome of host cell = can’t get it out so EXCEEDINGLY difficult to treat HIV **

89
Q

T or F. Only one HIV retrovirus can infect a cell

A

T! interference

90
Q

Process of HIV fusing with cell membrane

A
  • (conserved part of) virus particles binds to CD4 and co-receptor on T cell
  • viral envelope fuses with cell membrane allowing viral genome to enter cell

** variable loops extend over conserve regions; outward part of proteins = irrelevant to invasion strategy **

91
Q

This hides the fusogen in HIV

A

gp120; hidden until needed

92
Q

HIV uses these for entry

A

HIV infects cells that have CD4 (macrophages, DC, and Th cells) and a chemokine co-receptor

93
Q

People with this mutation are resistant to HIV infection

A

CCR5; but not completely bc a different chemokine receptor can be used

94
Q

CCR5 mutations

A

fairly common (10% caucasians in Europe - so not in Africa unfortunately)

95
Q

HIV fusion at the PM

A
  • HIV gp120 binds CD4 = conformational change that exposes the CCR5 receptor binding site
  • binding to the co-receptor induces a second conformational change (gp41 this time) that exposes the fusion peptide
    • > really hydrophobic part of the gp41 at end ends up inserting into membrane and now the virus and surface membrane are held together by protein and held closer and closer together until they fuse then dumping insides of virus into host cell membrane

** conformational change keep important parts hidden until milisec when it needs to insert fusion peptide into cell **

96
Q

Reverse transcriptase an Integrase of HIV

A
  • RT copies the ssrNA into dsDNA
  • I inserts DNA into genome

RNA that gets dumped into cell (two copies of it) gets copied into complementary DNA via reverse transcriptase; puts provirus right into chromosomal DNA of host; retroviruses can do this via reverse transcriptase to go from RNA to DNA

97
Q

Reverse transcriptase activity

A
  • tRNA serves as a primer for the first strand
  • RNase H is a host enzyme but reverse transcriptase uses this to cleave RNA strand and when making DNA strand, sits alongside RNA strand and cleaves it into fragments; can serve as primers for synthesis of new DNA that will happen as second part of replication process; taking two strands of RNA but making a double stranded DNA molecule out of it so can insert another genome
98
Q

T or F. Reverse transcriptase is error prone

A

T! We have exonuclease activity that will cleave mistakes before continue polymerization but RNA transcriptase continues on and ignores these mistakes; no error-proofreading activity!!!

So makes mistakes a lot ; one mistake every thousand base pairs on average

Infected w quasi species of viral particles; not just one sequence; lots of diff sequences! Every time it replicates, it makes a mistake

99
Q

Why does reverse transcriptase occur in the capsid?

A

To evade the immune system

100
Q

Cells infected with HIV must be ________ for the virus to replicate

A

activated
- transcription factor NFkB is turned on by the activation of infected T cells or macrophages
=> T cell activation induces low-level transcription of provirus
- RNA transcripts are multiply spliced, allowing translation of early genes tat and rev

** activation of T cell and macs = initiates viral synthesis ; only turned on in 1 in every 300 cells in an infected person **

101
Q

Assembly of new viral genomes (HIV)

A
  • Tat amplifies transcription of viral RNA; Rev increases transport or unspliced viral RNA to cytoplasm
  • the late proteins Gag, Pol, and Env are translated and assembled into virus particles which bud from the cell
102
Q

Gag gene (HIV)

A
  • group-specific antigen

- core proteins and matrix proteins

103
Q

Pol gene (HIV)

A
  • polymerase

- reverse transcriptase, protease, and integrase enzymes

104
Q

Env gene (HIV)

A
  • envelope
  • transmembrane glycoproteins
  • gp120 binds CD4 and CCR5; gp41 is required for virus fusion and internalization
105
Q

Tat gene (HIV)

A
  • transactivator

- positive regulator of transcription

106
Q

Rev gene (HIV)

A
  • regulator of viral expression

- allows export of unspliced and partially spliced transcripts from nucleus

107
Q

Baltimore classification

A

based on how many steps to mRNA

108
Q

+ strand viruses

A

can synthesize their own polymerases and don’t need to package it with the RNA
- flavi- and picornaviruses

109
Q

Why does a positive strand virus make negative strands?

A

negative strand is a template for more + strands

110
Q

+ vs - strand

A

Positive-sense viral RNA is similar to mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation

111
Q

Icosahedral structure, made up of four proteins (60 copies), encased only in capsid

A

Poliovirus

112
Q

This hides behind and stabilizes poliovirus capsid from inside

A

VP4

113
Q

Protease 2A in Polio (weird)

A

can make cleavage before release from polyprotein = folds on itself and cleaves itself out; not as efficient as it would be once its fully cleaved out but can do that initial cleavage

weird bc there’s already a protease that cleaves before putting in capsid

114
Q

Structure of polioviral 3Dpol polymerase

A
  • an RNA-dependent RNA polymerase
  • uses RNA template to base pair and copy the opposite/complementary strand (make RNA ; like how DNA is made)
  • unique to virus
  • specific for RNA template
  • copies viral RNA not host RNA
  • no proofreading activity so errors every 1/1000 base pairs; more potential for mutations and variants; most of the time replicates in intestines and shed back out
  • error rate limits size of virus
115
Q

RNA secondary structure is determined by the …

A

sequence

  • RNA secondary structure tells virus which RNA is its own
  • will hairpin back on itself
  • complementary base pairing along stems and leave loops ; RNA has very specific little stem loop structures at beginning that tells 3D polymerase which is viral and not host RNA
116
Q

Polioviral replication uses this as a primer

A

protein

- Tyrosine on 3AB protein serves as primer for initiation of new viral strand

117
Q

First step of translation in Poliovirus is

A

removal of VPg protein

118
Q

T or F. Genomic RNAs can serve as mRNAs for synthesis of new proteins

A

T!

119
Q

T or F. Polio is a human-only virus

A

T!

120
Q

Polio vaccines

A
  • inactivated vaccines (Salk) induce antibody response, rarely induce cellular immunity; ofte need a booster to induce a memory response
  • oral vaccine is live-attenuated (Sabin); it is synthesizing new virions and viral proteins that are targets of both humoral and cellular immune responses
121
Q

How is an attenuated virus made?

A
  • virus for humans may be attenuated by passage in non-human cell lines
  • pathogenic virus is isolated from a patient and grown in human cultured cells
  • the cultured virus is used to infect monkey cells
  • the virus acquires many mutations that allow it to grow well in monkey cells
  • the virus no longer grows well in human cells and may be a candidate for a vaccine
122
Q

Reversions of polio vaccine

A
  • P3 Sabin vaccine (oral) made an infectious virus that caused polio
  • although the AA changes did not remake the original virus, the new proteins could assemble a functional capsid and be infectious
  • continues to be a problem with this vaccine
123
Q

Poliovirus assembly

A

Proteins synthesize immediately come off into its structure (fold on themselves) = form higher order structures ; pathways happen very rapidly!! From little parts to making pentamers = makes sides of capsids ; pentamers assembles on themselves into shape of capsids = but unstable … create capsid and fall apart , etc.. In order to stabilize capsid is to get Rna inside capsid and once inside = RNA performs the last step of protein cleavage to clip capsid into a strong stable structure and the Rna itself is forming catalytic activity to cleave vp4 proteins that sit inside capsid and stabilizes capsid structure = how virus makes sure every capsid gets an RNA inside = falling apart is signal that not stable .. So must get RNA inside to stabilize

124
Q

How does poliovirus make sure that an RNA genome gets in every virion?

A

VP4 = inside = can’t see from outside; final cleavage done by catalytic RNA to cleave VP4 to make sure it gets genome into every single capsid that gets released; without genome - capsid is really unstable

125
Q

Synthetic polio vaccine

A
  • engineered for virus to create stable capsid w/out RNA inside
  • use capsid for vaccine without any danger of the vaccine-derived poliovirus outbreaks with live-attenuated virus = underway!
  • tricked protein to stabilize without RNA inside = much safer vaccine!
126
Q

Why is the integrase and reverse transcriptase packaged in the virion of HIV?

A

those are the first enzymes needed as soon as it enters cell bc takes its RNA strand (reverse transcriptase) to make ds DNA and uses integrase to put ds DNA in our genome
- once in our genome = uses our replication mechanisms, alt splicing mechanisms to make protein for itself (HIV genes from alt splicing used to make other proteins)

127
Q

This is a natural antiviral effector

A

TRIM22 (tripartite motif protein)

  • type 1 interferons restrict HIV replication; TRIM22 over-expression inhibited HIV replication
  • inhibited budding of virus-like particles containing Gag only, indicating that Gag was the target
  • catalytic AAs Cys15 and Cys18 of the RING domain are required for TRIM22 antiviral activity
128
Q

Simple single DNA virus ; uses host dep DNA polymerase to make second strand of DNA and uses host enzyme to make mRNa as well

A

Parvovirus

- infects dogs and cats

129
Q

T or F. Large DNA viruses encode their own enzymes

A

T!
DNA viruses = depends on size of virus whether it encodes enzymes, brings it in or uses host
- pox makes its own ; very large!

130
Q

Encodes own DNA pol but uses our RNA polymerase to make transcripts

A

Herpes virus

131
Q

Common mechanisms in exponential viral DNA replication

A
  1. template-directed
  2. each strand is copied beginning at the origins
  3. uses a DNA-dependent DNA polymerase

1-50 000 copies per cell; new DNAs serve as templates

132
Q

Generation of _____ for DNA synthesis is only present in the S phase

A

dNTP

  • entire DNA genome must be replicated to the ends
  • DNA dep DNA polymerase that we make is not present in the cell when they are in any other phase other than S phase, so virus has to trick cell to enter S phase
  • dNTPs aren’t present and hanging around; only present in S phase so again virus has to trick cell to go into S phase so polymerase are available AND NTPs in order to start DNA synthesis
133
Q

“End problem”

A
  • both viruses and humans have this problem
  • has to overcome this = each strand needs to be copied beginning of the origin – one side to the other otherwise it gets shorter every time
  • uses one strand to synthesize complementary strand = template directed
134
Q

Most common pattern of replication of DNA of host and viral genomes

A

(Semi-discontinuous) Bidirectional replication from an origin
- replication bubble gets bigger as they proceed

135
Q

RNA synthesis is initiated on the strand by a specialized called

A

Primase

136
Q

Describe the “End problem”

A
  • synthesis of leading strand starts from replication origin on RNA primer
  • lagging strand proceeds in short pieces as template becomes open (Okazaki fragments)
  • removal of the primer from the 5’ end creates a gap that cannot be filled
  • successive rounds of replication results in the loss of genetic material, unless specialized mechanisms are in place to deal with it
  • at end of our chromosomes = repetitive DNA or junk DNA that make up telomeres - do get shorter every time cell replicates but we have lots of it so not really an issue at that stage but determines the finite lifespan of cell
137
Q

How do viruses solve the end problem?

A

Viruses often circularize back on itself in order to solve this end problem
- enzyme will nick one strand and leave 3’ OH where new DNA strands can start = acts as primer to start next strand

138
Q

This helps package one genome

A

direct repeats at ends

  • proteins bind to specific sequences at ends
  • empty capsid binds to these proteins
  • DNA is stuffed in
  • a headful of DNA is stuffed in until proteins on other end are reached
  • cleavage of DNA
139
Q

T or F. Viruses have proofreading activity

A

F! They may or may not!

140
Q

Acyclovir

A

completely inhibits HSV-1

  • inhibits HSV DNA polymerase
  • looks like guanine but lacking base so halts replication
  • thymidine kinase adds phosphate to acyclovir make it active so it can be added as a terminal substrate
141
Q

Reproductive cycle of herpes simplex type 1

A
  • first proteins synthesized are transcriptional activators of genes
  • these transcripts make proteins needed later in synthesis
  • late proteins are required for capsid assembly and membrane proteins

** DNA is circularized in nucleus - transcripts are made and early transcripts made right away mostly make transcription factors **

142
Q

Herpes simplex virus latent infection

A
  • latent infection occurs primarily in neurons
  • transcripts produced from parts of the genome to produce proteins required to maintain latency

** latency inducing transcripts are translated as well to keep virus latent in those cells until they are activated by stress and initiation of other transcripts of virus **

143
Q

These defenses are most important in an acute infection

A

Innate

- life or death depends on innate

144
Q

Viral PRRs

A 
TLRs most important; intracellular PRRs
RIG I and MDA5 in cytoplasm of cells
- TLR3 = viral dsRNA
- TLR7/8 = viral ssRNA
- TLR9 = viral DNA
145
Q

Viruses that lyse the cell, or cause major disruptions to the morphology of the cell cause damage by direct cytopathic effect

A
  • Hepatitis B virus
  • Poliovirus
  • Measles virus
  • Influenza virus
  • Herpes simplex virus
146
Q

Viruses that can cause tissue damage by inducing cell-mediated immunity

A

Herpes simplex virus

147
Q

Neutrophils

A
  • phagocytic and first to arrive at sites of infection; causes pus
  • 70% of circulating cells
  • granules contain antimicrobial peptides including defensins
  • secretes alpha defensins
148
Q

Alpha defensins

A

potent antiviral secreted by defensins (neutrophils)

  • some are directly lytic to virus-infected cells
  • others bind to viral capsid and inhibit disassembly (prevent capsid from opening)
149
Q

How do macrophages recognize patterns on viral antigens?

A

by presence of sugars on glycoproteins and surface TLR receptors recognize viral capsid or membrane proteins

150
Q

T or F. All leukocytes have PRRs on their surface

A

T!

Macrophages have lots of PRR on surface and same with neutrophils but especially dendritic cells!!

151
Q

First step in Immune response

A

Detection by PRR on a dendritic cell

- activates DC to go to lymph node to start immune response

152
Q

What happens when TLRs recognize virus?

A

turns on interferons! key to turning on hundreds of antiviral genes
- instructing immune response what type of response to make by turning on interferons and cytokine genes

153
Q

Systemic effects of proinflammatory cytokines

A
  • act on hypothalamus
  • causes fever (most viruses) or increased body temp
  • fatigue, sleep
  • colony stimulating factors act on bone marrow to increase WBC output
  • acute phase proteins are made by the liver 100-1000-fold upregulation (some acute phase proteins have antiviral effects)
154
Q

Acute phase reactants

A

Proinflammatory cytokines induce liver to produce these

  • they are effector proteins made in response to an infection; often bind directly to virus
  • serum amyloid protein, C-reactive protein, fibrinogen, mannan-binding lectin
  • act as opsonins facilitating phagocytosis
155
Q

Mannan-binding lectin

A

MBL

  • binds to mannose on viral glycoproteins and acts as an opsonin
  • can also activate complement via the lectin pathway
156
Q

Main line of complement defense against animal viruses is due to antibodies against this

A

alpha Gal

  • why we don’t get viruses from our cats/dogs - due to Abs to this sugar that is often terminal sugar on glycoproteins produced in most animals other than primates
  • 2% of our Abs are directed against alpha gal = Abs already present in us when a virus causes from a non-primate animal and initiates complement pathway against those viruses = preventing infection and making it difficult for virus to jump from non-primate to human
  • but can cross over if overcome this defense
157
Q

Interferon alpha

A
  • produced by leukocytes
  • induced by virus infections, dsRNA
  • type I interferon
158
Q

Interferon beta

A
  • produced by fibroblasts, epithelial cells
  • induced by virus infections, dsRNA
  • type I interferon
  • “turn on a lot of antiviral genes; 300+ interferon stimulated genes (some we know some we don’t)”
159
Q

Interferon gamma

A
  • produced by T cells, NK cells
  • induced by antigens, mitogens, IL-2, IL-12
  • type II interferon
  • “antiviral but In a diff way”
160
Q

Mitogens

A

non-specific stimulators of lymphocytes

161
Q

TNF-alpha

A

activated macrophages make this -> NK cells

162
Q

IFN-y

A

made by activated NK or T cells -> macrophages

163
Q

“Warning proteins” made by leukocytes

A
  • interferons
  • made especially by DC if they detect virus
  • interferon alpha and beta are made by cells after recognition of ssRNA or dsRNA or viral capsid proteins or viral capsid proteins
  • it binds to receptors on other cells and turns on the antiviral program
164
Q

Professional interferon producing cells

A

DCs

165
Q

Type I interferons

A
  • have local effects on other immune cells
  • ‘antiviral state’ induced in neighbouring cells (ex: TRIM22 inhibits trafficking of HIG gag proteins)
  • interferon makes u feel like crap when sick
  • great drug bc virus induce cells to make this – turns on lots of protective things ; but not for a long time due to whole body malaise
166
Q

Antiviral program in neighbouring cells by Type I IFN

A

over 100 proteins induced

  • 2’ -5’ synthetase is activated to make oligoadenylate (Ax7) which in turn activates RNase L (adenine nucleotide from DNA - takes and strings them all together)
  • RNase L degrades cellular and viral mRNA
  • dsRNA activated protein kinase (Pkr) stops new protein synthesis
167
Q

Aberrant innate immune response to 1918 influenza caused severe lung damage

A
  • recruited so much leukocytes to lungs – filled lungs with cells = breathing made impossible; no airways left in tissue
  • recruitment of leukocytes is so extreme = release cytokines and recruits more leukocytes = cytokine storm!
  • recruiting way too much of WBCs on the scene of infection; stopped experiment early bc animals were too sick
  • too much inflammation = pathology
168
Q

Pandemic strain of flu vs. Seasonal flu

A

pandemic strain of flu = VERY overactive immune response = persistent activation of cytokines = also shut down the production of interferon early in the immune response ; without interferon, the antiviral effect in tissues was much less ; overactivation of proinflammatory cytokines recruiting so many leukocytes that it resulted in severe tissue damage

169
Q

On average, how many peptides from a virus will fit into any MHC class I?

A

one or two

  • peptides bound by MHC I allele share the ‘contact’ AAs
  • MHC genotype will make some people more resistant to certain viruses
170
Q

These are potent activators of naive cytotoxic T cells

A

DC

- measles, HIV, and influenza infect DCs

171
Q

CTL made without this from TH cells do not become memory CTL

A

IL-2

172
Q

Immunosenescence

A

refers to the gradual deterioration of our immune system as we get older.
- it involves our capacity to respond to infections and maintain our long-term immune memory that was acquired (usually in our early life) either by infection or vaccination

173
Q

Engagement of MHC I by this inhibits killing

A

NK inhibitory receptor

  • down-regulation of MHC I results in activation of NC killing
  • viruses love to downregulate or shut down the MHC class I so doesn’t get inhibitory signal and NK will kill virus
174
Q

Which vaccine elicits a better immune response?

A

live-attenuated

  • taken up by dendritic cells and in the DC, the live attenuated virus which can synthesize new proteins = get expressed on MHC I and recruit naïve CD8 T cells
  • live attenuated viruses covered in all kinds of PAMPs = activated PRRs which activate dendritic cells to make costim molecules = upregulated in order for DC to be activated and give signal to CTL
175
Q

Polysaccharide vaccines

A

or carbs

  • induce a T-cell independent antibody response
  • low affinity antibodies and no memory
176
Q

Live attenuated, viral vectors, and nucleic acid vaccines

A
  • induce both MHC I and MHC II antigen presentation and PRRs expressed by DCs through several PAMPS including peptidoglycan, lipopolysaccharide and bacterial/viral RNA and DNA
  • generally induce robust CD8 and CD4 T-cell responses, high antibody titers, and good memory
177
Q

Killed whole-organism vaccines

A

humoral; activate DCs through the same PAMPs and induce good CD4 and B-cell responses

178
Q

Protein vaccines, viral-like particles, and glycoconjugate vaccines

A
  • may need an adjuvant for optimal DC activation and CD4 T-cell priming
  • some adjuvants such as polyinosinic:polycytidylic acid or saponins can also induce CD8 T-cell responses to submit vaccines through cross-presentation mechanisms
179
Q

RNA vaccine

A
  • typically modified in a way that its put into nanoparticles that allows it to get into APCs; can be ssRNA or dsRNA
  • RNA gets taken up by APC that RNA can be used to synthesize protein = some get chopped up and put on newly synthesized MHC I molecules to recruit CD8 T cells
  • NOT live attenuated vaccine bc no viral replication (no live virus); RNA is delivered to cell and cell uses our transcriptional machinery to synthesize protein
  • but it behaves like a living thing in the same way that live att does bc protein gets presented on MHC I and recruits CD8 T cells; only happens when proteins are synthesized!! happens w RNA bc given template
180
Q

T or F. CTL IL-2 is sufficient to make memory cells

A

F! In order for CTLs to become memory cells they have to get IL-2 from TH cells; if they get IL-2 from their own synthesis that makes effector cells that will live for a week but they never become memory cells

181
Q

Monoclonal vs Polyclonal antibodies

A
  • Monoclonal Abs are made in the lab; Sera is polyclonal

- monoclonal recognizes one epitope (one specificity); poly- recognizes many

182
Q

3D structure recognized by antibody

A

epitope

- unique specificity; can be carb or protein

183
Q

An in vitro test in which antibodies bind to virus and prevent the infectious cycle

A

Neutralization assay
- done with a monoclonal antibody or polyclonal antisera from a vaccinated person, or someone who has survived an infection (expected to have made neutralizing antibodies)

184
Q

Virus neutralization

A

free virus particles are susceptible to neutralizing antibodies

185
Q

Possible mechanisms of neutralizing antibodies:

A
  1. steric interference with receptor
  2. fix capsid so pH dependent uncoating is blocked
  3. structural changes so that uncoating is blocked
186
Q

Best neutralizing Abs

A

those that inhibit docking of receptor presenting entry at v early stages; steric interference with binding to receptor for attachment = block this step!!

187
Q

Presence of antibodies against HIV is used as a diagnostic HIV test

A
  • Western blot to detect anti-HIV antibodies in patient serum
  • viral proteins are separated on a polyacylamide gel
  • proteins are transferred to a membrane
  • primary antibody is patient serum containing anti-HIV antibodies
  • secondary antibody recognizing human IgG is labelled
  • visualization on X-ray film
  • viral proteins are bound by the human Ab, and detected with the labelled anti-human IgG antibody
188
Q

If HIV positive individuals make a lot of antibodies, are any of them effective?

A

Yes, sometimes!

  • HIV but no symptoms for 6 years for one male
  • B cells expressing Abs were isolated from this patient
  • monoclonal antibody B12 from this patient is a broadly neutralizing antibody (neutralized many strains of HIV)
  • isolated B12 antibody prevented infection in macaques
189
Q

HIV neutralizing antibody: B12

A

has a projection on its variable region that allows it to bind snugly to HIV’s gp120 protein

  • B12 prevents gp120 from docking to receptors CD4 and CCR5
  • rare!
190
Q

Why do most HIV antibodies fail?

A
  • the structure of HIV-1 envelope glycoprotein contributes to evasion from the immune system
  • variable regions cover the conserved regions; extensive glycosylation
  • important epitopes are hidden within the molecule, such as the fusion peptide
191
Q

The antibodies we make to the extensive glycosylation of HIV is not as effective. Why?

A

extensive glycosylation/lollipop structure = blocking access of Abs to this molecule; we can make Abs to carbohydrates but those are in the absence of T cell help bc need protein to be chopped up to be presented to T cell to make IL-2 in order to make good Abs
- so these Abs we make to these are T-independent and not as effective

192
Q

The two receptor mechanism of entry is an evasion strategy for HIV

A
  • important epitopes of gp120 are completely hidden until fusion
  • only exposed for a moment during the fusion process (bind to CD4 and CCR5 - conformation change - fusion peptide binds to host)
  • chemokine receptor was probably the OG receptor and the interaction with CD4 evolved later
  • very effective strategy!
193
Q

Viral (HIV) escape from neutralizing antibodies

A

in vitro experiments:

  • monoclonal Ab to V2 domain of gp120 resulted in V2 mutants (region can totally change!)
  • polyclonal antisera to Env - resulted in gp41 mutation causing large conformational change in gp120
194
Q

HIV neutralizing antibodies made in vivo:

A
  • 95% of the changes in the nucleotide sequence made changes in the AA sequence of the env glycoprotein (replacement mutations); only 5% were in third nucleotide of codon (silent) – evidence of selection!
    taking sequential serum samples - serum could neutralize virus in vitro from the starting inoculum but not the variants that arose later in the infection
  • virus in which the variable regions were removed were neutralized rapidly
195
Q

HIV - evolving glycan shield

A

virus mutated locations of the glycosylation sites

196
Q

The structure of peptide antigens bound by an MHC I allele

A
  • an epitope bound by class I is a linear 9 amino acid sequence from within the protein
  • viral proteins can be presented if they fit
  • each peptide varies except at anchor residues
  • peptides bound by one allele
197
Q

HIV is evolving to eliminate CTL epitopes (especially for common HLA alleles)

A
  • common alleles like HLA2 = no peptides that can be presented by that peptide binding cleft for HIV - has evolved away from it completely
  • effective CTL exert strong selective pressure on the virus; viral variant epitopes that escape these CTLs by failing to bind to HLA or to interact with TCR have an advantage in vivo
  • other responses are less effective and are not associated with escape, so no selective pressure on virus to mutate
  • if an effective CTL response is directed against an epitope region that constrained functionally or structurally, there may be no selection or slow selection bc a mosaic of mutations is require for escape to occur
198
Q

Immunodominant epitopes

A

CTL immune response tends to focus on a few epitopes originally seen
- sometimes called ‘original antigenic sin’ (CTL tends to focus on best epitopes first)

199
Q

How did the ‘Berlin patient’ rid himself of HIV?

A
  • irradiation to destroy immune system before transplant
  • bone marrow transplanted with cells homozygous for CCR5 mutation
  • graft-vs-host disease may have killed last of his infected T cells
  • MHC is HLA-B57
200
Q

Points of action of antiretroviral drugs

A
  • drugs that inhibit entry, reverse transcriptase inhibitors, protease inhibitors, etc.
  • much slower for virus to escape if giving drugs in combination of two or three different drugs depending on individual (which ones they tolerate the best)
201
Q

HAART

A
  • highly active antiretroviral therapy
  • combo of 3+ antiviral drugs
  • 2 different kinds of nucleoside reverse transcriptase inhibitors
    > AZT (3’-Azidothymidine)
    > 3-TC (2’3’-Dideozy-3’-thiacytidine
  • protease inhibitor
    > Darunavir: binds and blocks active site of the HIV protease
202
Q

Pros and cons of HAART

A

Pros:

  • greater than 90% viral suppression
  • viral suppression is prolonged (~2 yrs) compared to using only a single antiviral drug (3-6 months)
  • increased lifespan from 8-10 yrs to 17-20 yrs

Cons:

  • does not work for everyone
  • serious side effects (headaches, peripheral neuropathy) so ~15% of people cannot take these antivirals due to side effects
  • expensive (now fewer pills needed at least)
203
Q

Vorinostat

A

deacetylase inhibitor; opens chromatin; gets HIV out of that reservoir = biggest challenge!

204
Q

Shock and kill method for HIV

A
  • aimed to reawaken latent reservoir with drugs called LRAs to expose the infected cells to the killing power of the immune system (but CD8 T cells prefer to kill cells infected with defective virus and have little effect on the reservoir cells)
  • involves activating viral replication (vorinostat - leads to activation of HIV genes = increase in synthesis of viral RNA)
    then HAART to protect uninfected cells from becoming infected
  • maybe one day used to “awaken” dormant HIV
  • infected cells would then be killed by either virus itself or by patient’s immune system
  • hasn’t worked the best so far…
205
Q

PRIME, shock, and kill

A
  • drug given to patient to prime or prepare the reservoir to submit to being killed by CD8 T cells
  • then as usual, LRAs (latency-reversing agents) are added to awaken the reservoir and mark those cells for killing by immune system
206
Q

T or F. HIV-2 more prevalent than HIV-1

A

F! HIV-2 also causes AIDs but not as prevalent as HIV-1 which causes most disease and resembles the chimpanzee virus
- HIV-2 did not acquire the same ease of transmission that HIV 1 has; HIV-1 = worldwide HIV pandemic

207
Q

Zoonosis

A

transfer of a pathogen from non-human animals to humans and subsequent spread of the pathogen between humans

208
Q

T or F. Negative strand viruses always package RNA-dependent RNA polymerase in infectious particles

A

T! Measles, Ebola, Influenza
- non-infectious if no RNA dep RNA pol in the virion
bc can’t initiate a round rep or translation of that RNA

209
Q

Virus spillover from wildlife

A

pathogen spillover to humans is typically associated with the use of bushmeat and direct contact with tissues and/or bodily fluids through handling and eating of infected animals (ex: duiker, primates, or fruit bat)

  • human-to-human transmission has been associated with traditional burials
  • bats have Abs to ebola; so have been infected in the past
  • fruit-eating bats, eat fruit but can’t ingest it all, chew and spit out pulp and that pulp gets eaten by other animals under tree like primates and duiker and ppl eat bush meat such as primates and duikers = primary way getting ebola possibly
  • and humans could possibly get it from bats too but a lot harder to get from bats directly vs primates bc bats have the alpha gal surrounding glycoproteins whereas primates don’t
  • and we make antibodies against alpha gal and initiates complement-mediated killing of virus and infected cell
  • healthcare professionals were most at risk bc of lack of PPE, etc.
210
Q

What makes Ebola so pathogenic?

A
  • macs and Dcs are infected
  • high proinflammatory cytokines from macs recruit more macs and DCs
  • vascular endothelium gets infected and becomes leaky
  • lymphocytes are killed in spleen and lymph nodes
  • hepatocytes are killed and clotting factors depleted = more bleeding!
211
Q

Merck’s vaccine

A
  • VSV-ZEBOV
    consists of a virus that mainly infects animals called the vesicular stomatitis virus (VSV)
  • in the vaccine, one gene of VSV has been replaced with the gene that codes for the outer protein of the Zaire Ebola Virus
  • uses a viral vector and engineer it to have spike protein from Ebola (outer protein that’s involved in receptor attachment)
  • time lag avoids the need to use a placebo
  • doctors used same vaccinating strategy to eradicate smallpox
212
Q

ZMapp (against Ebola) mechanism

A
  • three monoclonal Abs that were directed at spiked proteins
  • neutralizing Abs that bind to spiked proteins upon mediated cell entry
  • trigger complement-mediated killing of infected cells
  • expensive to make so not deployed in Africa

IMIN 200 (3 decks)

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