Viruses and their treatment Flashcards
1
Q
after the initial acute infection, the course of an infection is determined largely by
A
the immune response of the host –> clearance of persistence
1
Q
what is antigenic variation
A
viruses can vary their surface antigens - allows the virus to escape neutralization by pre-existing antibody
2
Q
what is the receptor for influenza viruses
A
carbohydrate - sialic acid
2
Q
which virus causes croup
A
parainfluenza
3
Q
what does post-translational cleavage of viral proteins involve
A
usually needs virus-coded proteases
4
Q
how does HCV inhibit T cell priming by DC
A
blocks cytokine induced maturation of DC
5
Q
how do viruses attach to cells
A
viral attachment protein binds specifically to a receptor (protein or carbohydrate) on the plasma membrane
5
Q
which viruses infect the pharnx
A
adenovirus
6
Q
why is tryptase Clara so important in influenza
A
HA must be cut for the influenza virus to be infectious - this enzyme is only in our RT –> stops it from infecting systemically
7
Q
what is antigenic shift?
A
sudden appearance of an influenza A virus of a new HA (and sometimes a new NA) within the human population
8
Q
how does budding of virons happen
A
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
Q
barriers to infection in via the alimentary tract
A
- sequestration in intestinal contents
- mucus
- acidity
- intestinal alkalinity
- proteolytic enzymes secreted by pancreas
- lipolytic activity of bile
- IgA
- scavenging macrophages
8
Q
what are the three outcomes when viruses infect a foetus
A
- death and abortion by cytocidal viruses
- developmental abnormalities by non-cytocidal viruses
- immunological tolerance - but a carrier
9
Q
2 ways viruses can penetrate cells
A
- lipid viruses - can fuse with the host cell membrane and release virus nucleocapsid directly into the cytoplasm - entry via endocytosis
9
Q
mechanisms of viral spread throughout the body
A
- local spread on epithelial surfaces - subepithelial invasion and lymphatic spread - spread via bloodstream - viremia - neural spread
10
Q
action of rotovirus
A
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
Q
types of virus-induced changes in cells
A
- transformation to tumour cells - lytic infection - chronic infection - latent infection
12
Q
how does virus enter the cytoplasm once inside endosomes
A
- 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
Q
which viruses infect the URT
A
rhinovirus coronavirus adenovirus measles
13
Q
assembly of non-enveloped animal viruses - 2 strategies
A
- 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
Q
what are the mechanisms of viral-induced damage to tissues and organs
A
- death of cells resulting directs from viral replication (cyotcidal virus) - death resulting from toxicity of viral products - initiation of apoptosis - loss of function
13
Q
How does vaccinia virus inhibit T cell priming by DC
A
- 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
Q
where do DNA and RNA viruses usually replicate in the cell - what are the exception?
A
DNA - in the nucleus - exception poxvirus RNA - in the cytoplasm - exception influenza virus
16
Q
where is translation of viral proteins done
A
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
