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Flashcards in Viruses and their treatment Deck (119):
1

after the initial acute infection, the course of an infection is determined largely by

the immune response of the host --> clearance of persistence

1

what is antigenic variation

viruses can vary their surface antigens - allows the virus to escape neutralization by pre-existing antibody

2

what is the receptor for influenza viruses

carbohydrate - sialic acid

2

which virus causes croup

parainfluenza

3

what does post-translational cleavage of viral proteins involve

usually needs virus-coded proteases

4

how does HCV inhibit T cell priming by DC

blocks cytokine induced maturation of DC

5

how do viruses attach to cells

viral attachment protein binds specifically to a receptor (protein or carbohydrate) on the plasma membrane

5

which viruses infect the pharnx

adenovirus

6

why is tryptase Clara so important in influenza

HA must be cut for the influenza virus to be infectious - this enzyme is only in our RT --> stops it from infecting systemically

7

what is antigenic shift?

sudden appearance of an influenza A virus of a new HA (and sometimes a new NA) within the human population

8

how does budding of virons happen

patches of viral envelope glycoproteins accumulate in the plasma membrane. Capsid proteins and nucleic acid condense direcly adjacent to the cell membrane - the bulges out

8

barriers to infection in via the alimentary tract

- sequestration in intestinal contents

- mucus

- acidity

- intestinal alkalinity

- proteolytic enzymes secreted by pancreas

- lipolytic activity of bile

- IgA

- scavenging macrophages

8

what are the three outcomes when viruses infect a foetus

- death and abortion by cytocidal viruses

- developmental abnormalities by non-cytocidal viruses

- immunological tolerance - but a carrier

9

2 ways viruses can penetrate cells

- lipid viruses - can fuse with the host cell membrane and release virus nucleocapsid directly into the cytoplasm - entry via endocytosis

9

mechanisms of viral spread throughout the body

- local spread on epithelial surfaces - subepithelial invasion and lymphatic spread - spread via bloodstream - viremia - neural spread

10

action of rotovirus

infect and destroy epithelial cells of the intestinal villi and M cells causing inflammation and diarrhoea. Also secretes NSP4 protein that increases fluid secretion even more

11

types of virus-induced changes in cells

- transformation to tumour cells - lytic infection - chronic infection - latent infection

12

how does virus enter the cytoplasm once inside endosomes

- triggered by low pH of these vesicles --> induces conformational change in the viral proteins that exposes a fusion region - cause lysis of the endosome

12

which viruses infect the URT

rhinovirus coronavirus adenovirus measles

13

assembly of non-enveloped animal viruses - 2 strategies

- spontaneous assembly of capsid proteins around the nucleic acid genome - may require proteolytic cleavage to induce the final conformation in the capsid proteins of the viron

13

what are the mechanisms of viral-induced damage to tissues and organs

- death of cells resulting directs from viral replication (cyotcidal virus) - death resulting from toxicity of viral products - initiation of apoptosis - loss of function

13

How does vaccinia virus inhibit T cell priming by DC

- it encodes a homolog for the cytoplasmic tail of TLR4 that inhibits signal transduction to initiate maturation of the DC - blocks cytokine induced maturation of DC

15

where do DNA and RNA viruses usually replicate in the cell - what are the exception?

DNA - in the nucleus - exception poxvirus RNA - in the cytoplasm - exception influenza virus

16

where is translation of viral proteins done

by the ribosomes of host cell

17

what produces type 2 interferons

NK cells and T cells

18

What is a quasispecies

As a result of mutation, each virus that comes out of a person is slightly different to another infected person

19

what are viruses that infect the respiratory tract which spread systemically

- mumps - measles - rubella virus - varicella-zoster

20

what produces type 1 interferons when infected by virus?

- macrophages - DC cells - tissue cells

20

adaptive immune response to influenza virus

- CD8+ cytotoxic T cells--> kill virus-infected cells - antibody - to HA and NA

21

what do interferons do to viruses?

inhibits translation of viral proteins by activating PKR - activated by dsRNA

21

how does the influenza virus give us immunity

induces antibodies (not cytotoxic T cells)

22

which viruses can be caught when coming through the birth canal

HSV varicella CMV coxsackie

23

how does RSV evade CD8 T cell recognition

decreases the Class 1 MHC gene transcription

24

which viruses evade the immune system by evading CD8 T cell recognition

HIV, HSV, CMV, adenovirus, RSV, EBV

25

release of non-enveloped animal viruses

only released when virions accumulated in such a number that the cell lyses

25

how does influenza bind to cells

HA binds to sialic acid-containing receptors on non-ciliated respiratory epithelium (alpha-2-6 linkage to galactose)

25

Example of viruses that bud out of the cell membrane and are secreted out of the cell membrane

Influenza - Budds out Coronavirus - secreted out

26

types of immunopathology caused by viral infection

- antibody mediated pathology - T cell mediated pathology

27

typical influenza symptoms

fever/chills cough headache muscle aches fatigue loss of appetite

28

which viruses if infected during foetal life causes developmental abnormalities

rubella CMV

29

what is the difference between early and late proteins made by viruses

early proteins are usually non-structural late proteins are usually structural

29

what are the 2 main mechanisms for viruses evading the immune system?

- not being recognised - interfering with the functioning of particular immune mechanisms

30

which viruses evade the immune system by inhibiting T cell priming by DC

vaccinia, HCV, HSV, measles, CMV

30

what is antigenic drift in influenza virus

mutations and selection of the HA and NA proteins --> pre formed antibodies dont recognise these

31

baltimore classes

1. ds DNA 2. - or + ssDNA 3. ds RNA 4. + mRNA 5. - RNA 6. + RNA

31

what are the targets (and example of the virus) of inhibiting T cell priming by DC

- block cytokine induced maturation of DC (vaccinia and HCV) - interfere with proteins on MHC and costimulatory molecules needed for T cell priming (measles and CMV) - blocks signal transduction from Toll-like Rs (HSV) on DCs - encode a homolog of the cytoplasmic tail of TLRs on DCs

32

what is the latent and eclipse periods of viral replication due to

when virus broken down into its particles and then amplication before genome assembled for release and spread

33

how does CMV protein evade CD8 T cell recognition

CMV protein binds to TAP transporter on luminal side and prevents peptide translocation to ER

33

why are influenza pandemics rare?

because the virus has to come from birds - where the receptor is alpha-2-3 Gal. Therefore they receptor specificity of the virus has to change before it can affect us

34

why doesnt rhinovirus spread throughout the RT

because it is unstable at higher temps of the LRT

35

what type of viruses tend to survive in the alimentary tract

viruses with multiple capsids that are acid and bile resistant with no envelope

37

what are cytopathic effects

morphological changes occurring in cells as a result of infection seen by light microscopy

38

structure of influenza virus

- enveloped virus (HA and NA) - has 8 segments of -ve sense ss RNA - Has M1 matrix protein - Has M2 ion channel

40

routes of entry of viruses

- conjunctiva - respiratory tract - alimentary tract - urogenital tract - parenteral inoculation - skin (via wound)

42

what clinical sign is diagnostic of measles

Koplick spots - where the virus is initially replicating - where the lymphocytes are coming in to fight the infection (the spots are the lymphocytes)

44

determinants of viral tropism

- availability of receptors - optimal temperature for replication - stability in extremes of pH - ability to replicate in macrophages and lymphocytes - polarized release - presence of activating enzymes

45

if tryptase Clara does not work on influenza, what happens

virus cannot escape the endosome

46

flu spread by

droplet inhalation

48

what is an example of cytopathic effects

inclusion bodies

48

which viruses infect the alveoli

RSV parainfluenza 3 adenovirus

49

currently, what does our influenza vaccine contain

H1N1, H3N2 and influenza B

50

what is the receptor for rhinoviruses

protein - ICAM-1

51

outcomes of viral infection

- fatal - full recovery - recovery but permanent damage - persistent infection

52

incubation and infectious periods of flu

incubation = 1-5 days infectious = 5-6 days

53

what cells does the measles virus infect and what is its route through the body

local macrophages, lymphocytes and DC --> then draining lymph nodes --> then enter circulation and amplify in lymphoid tissue --> then returns to epithelial cells in lung and mouth

55

first thing that virus has to do for replication

translation of nonstructural proteins ( including RNA-dependent, DNA polymerase) --> forms a polyprotein which autocleaves itself

55

how can the flu lead to getting a secondary bacterial infection

viral replication can then go onto to replicate inside ciliated epithelium --> no elevator to stop normal commensals of the URT to move down into the LRT and colonise

56

targets of vaccine-induced immunity to the influenza virus

- antibody binds to HA - blocking attachment - antibody to NA - blocks efficient release

57

what is the ancestral hosts of influenza type A

aquatic birds

59

order of genome replication and protein synthesis in viral replication

1. translation of nonstructural proteins 2. autocleavage and further cleavage of polyprotein 3. synthesis of minus strand 4. synthesis of new plus strands

60

where does influenza multiply

in the epithelial cells of the upper and lower respiratory tract, but particularly large airways

61

attachment of HIV virus

2 receptors - initial and then closer attachment - initial attachment via gp120 to CD4 protein on T cells --> conformational change in the glycoprotein - exposing the hydrophobic portion of GP41 protein and recruits chemokine receptors - binding of chemokine receptor to GP41

61

Why are pigs so scary for influenza?

has mixed alpha-2-6 and alpha 2-3 linked SA receptors --> therefore can get coinfection with 2 viruses --> swapping of genes (reassortment) --> infectious to humans

62

which viruses infect the bronchioles

RSV, parainfluenza 3

63

How does fusion of the endosome with the influenza viral envelope occur

as the endosome becomes more acid - the HA changes conformation leading to fusion --> escape of the 8 viral RNPs

64

Example of viruses that cause lysis of the cell

Enterovirus, reovirus

66

the infectious process can be halted by:

- antibody - blocks uptake and/or neutralises progeny virus - killing the infected cell by cytotoxic T cells, NK cells or Ab-mediated mechanisms - IFN - blocking the replication cycle by specific antiviral drugs

67

current influenza viruses infecting humans

H1N1 H3N2

69

which cells do viruses infect in the alimentary canal

- enterocytes - M cells

70

function of NK cells

spontaneous cytotoxicity towards a variety of tumour cells and virus-infected cells - major source of IFN-gamma

71

action of HA and NA

HA - has 3 R binding pockets that bind and engage with sialic acid and gets into the cell NA - has 4 subunits that cuts off the sialic acid receptors from the cell surface

72

viral genomes are continually changing as a result of

- mutation - recombination - reassortment

73

where does glycosylation of envelope glycoproteins occur

in the RER and Golgi vesicles --> results in their deposition in the cell plasma membrane

75

how does HSV inhibit T cell priming by DC

it blocks signal transduction from TLR on DC

76

6 steps of viral replication

1. assembly 2. penetration 3. uncoating 4. amplification - genome replication, RNA synthesis and protein synthesis 5. assembly 6. release

78

what is receptors of measles virus

CD150 and CD46

80

what makes an avian influenza virus highly pathogenic

have different cleavage sites that can be cut by an enzyme found in all cells --> systemic spread

82

How does HIV evade CD8 T cell recognition

- by making Nef protein - inducing the endocytosis of Class 1 MHC molecules to remove presentation of antigen - antigenic variation of epitope presented by MHC - class 1 MHC gene transcription decreased

84

how does antigenic variation arise

arise spontaneously through errors in RNA replication giving rise to point mutations in the genes

86

what are viruses that infect the respiratory tract that stay localised

- rhinovirus - Respiratory syncytial virus - influenza virus

87

drug names of virals that act by blocking the action of NA of influenza

Relenza and Tamiflu

89

what does the stage of uncoating entail

the release of the viral genome from its protective capsid to enable the nucleic acid to be transported within the cell and transcribed to form new progeny virus

90

how do you get the symptoms of flu?

IL-1 --> fever IFN--> malaise, headache and muscle aches

91

drug names of antivirals that act on the ion channel of influenza virus

amantadine and rimantadine

93

3 ways viruses can escape the actions of interferons

- produces small stretches of RNA that bind to PKR preventing interaction with dsRNA - virus-encoding protein binds to dsRNA preventing PKR activation - virus encoded homologue of eIF2 (translation factor) which competes for PKR inhibiting phsophorylation

94

What is antibody mediated pathology of viral infections

- Ab-dependent enhancement of infection - Antigen-Ab complexes - deposition causes damage

95

who is particularly susceptible to H1N1 flu

pregnant women obese indigenous populations

96

How does adenovirus evade CD8 T cell recognition

- adenovirus protein binds MHC peptide complex and retains it in the ER - class 1 MHC gene transcription decreased

98

how does HSV evade CD8 T cell recognition

HSV protein binds to cytosolic side of TAP transporter and prevents peptide translocation to ER

99

how are there different subtypes of Type A influenza

- differ in the form of HA and NA they encode (have similar internal proteins)

100

functions of type 1 and 2 interferons against viruses

- inhibits viral replication - activates NK cells (1) Activates macrophages (2) - enhances MHC class 1 expression targets

101

how can viruses cause host damage

- viral induced damage - consequence of the immune response: --> immnopathology, immunosuppression, autoimmunity

102

how are enveloped viruses assembled and released - 2 strategies

1. budding 2. utilise the secretory pathway

103

targets of influenza antiviral drugs

1. ion channel blockers - inhibits the function of the M2 ion channel, preventing endosome escape of RNPs 2. NA inhibitors

104

which virus evade the immune system by affecting NK cell activity and how

human CMV - encodes an MHC class-1 like molecule that is expressed on surface of infected cell and delivers a negative signal to NK cell but cannot itself present peptides to CD8 T cells

105

viruses that infect the GI system but then spread systemically

hep A poliovirus

106

how does HIV penetrate the cell

the hydrophobic region of gp41, once exposed, can initiate fusion of the two membranes

107

primary and secondary phases of viremia

- primary - when virus first enters the blood (only a small amount of virus) - secondary - when it gets to target organ, the virus amplifies and then released into bloodstream again in large loads

108

what is special about type A influenza

it also infects other species (type B and C don't)

110

barriers to infection in the respiratory tract

mucus, cilia, alveolar macrophages, temperature gradients, IgA

111

How does antigenic shift cause pandemics?

complete lack of protective immunity --> rapid global spread

112

definition of tropism

anatomical localization of infection

113

humans with NK cell deficiency are highly susceptible to which viruses

varicella and CMV (herpes virus family)

114

What are inclusion bodies

Represent accumulated viral proteins at he site of viral assembly

115

how does EBV evade CD8 T cell recognition

it inhibits the proteosome

116

activation mechanism of NK cells

- activation receptor recognizes molecules on the cell surface that are there as a result of virus infection and will send a killing signal - the inhibitory receptor binds to MHC class 1 molecule on the tarted cell - if engaged will override the killing signal

117

how does the measles and CMV inhibit T cell priming by DC

blocks T cell stimulation - by interfering with the proteins on MHC and costimulatory molecules needed for T cell priming

118

how long does the flu normally last

~7 days - longer in those who have poor IS

119

how are NK cells activated

in response to IL-12 or IFN-alpha/betta