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Virology > Q4 > Flashcards

Q4 Flashcards

1
Q

How to study virus infection and disease in mouse?

A
  1. Mice with new receptors
  2. Mice with complete viral genome
  3. Mice that express individual viral genes
  4. Clonal T cell receptor
  5. Immune mediator deletion
  6. Overproduction of immune mediator
  7. Deletion of immune cell
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2
Q

What are the two general ways of studying host response to infection?

A
  1. Human viruses in animals
  2. Animal viruses that resemble human infections
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3
Q

What is viral virulence?

A

The capacity of a virus to cause disease in a host

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4
Q

What are the different ways that virulence can be quantitated?

A
  1. Mean time to death
  2. Mean time to appearance of symptoms
  3. Measurement of fever, weight loss
  4. Measurement of pathological lesions (poliovirus), blood CD4+ lymphocyte reduction (HIV-1)
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5
Q

For what virus infection are pathological lesions quantified?

A

Poliovirus

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6
Q

For what virus infection, there is a reduction in blood CD4+ lymphocyte?

A

HIV-1

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7
Q

Which of Poliovirus type I and type II is more virulent, and why?

A

Type II is more virulent, when mice is inoculated intracerebrally (5 per virus), 7 days post-infection mice start dying, and within 15 days, all the mice are dead, all type I infected mice are alive

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8
Q

Two general methods for measuring viral virulence

A
  1. Measurement of survival
  2. Measurement of pathological lesions
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9
Q

Which among the five viruses seen for pathological lesions had relatively the highest neurovirulence score? Which CNS parts had the highest?

A

Japanese encephalitis virus
Cerebrum, brain stem; followed by spinal cord

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10
Q

Which among the five viruses seen for pathological lesions had relatively the lowest neurovirulence score?

A

Dengue

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11
Q

Why can viral virulence be compared only between similar types of viruses?

A

It is a relative property

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11
Q

What are the properties of viral virulence?

A
  1. Cannot compare virulence of different viruses
  2. For similar viruses, assays has to be same
  3. Influenced by dose, route of infection, gender, species, susceptibility of host, age
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12
Q

Example of a virus that is virulent when intracerebrally inoculated but not when subcutaneously inoculated (because it cannot reach the brain)

A

Tahyna virus

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13
Q

How many wild-type la crosse virus is needed to kill 50% of suckling mice when inoculated intracerebrally?

A

~1

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14
Q

How many wild-type la crosse virus is needed to kill 50% of suckling mice when inoculated subcutaneously?

A

~1

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15
Q

How many wild-type la crosse virus is needed to kill 50% of adult mice when inoculated intracerebrally?

A

~1

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16
Q

How many wild-type la crosse virus is needed to kill 50% of adult mice when inoculated subcutaneously?

A

~10

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17
Q

How many attenuated la crosse virus mutant is needed to kill 50% of suckling mice when inoculated subcutaneously?

A

> 10^5

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18
Q

How many attenuated la crosse virus mutant is needed to kill 50% of suckling mice when inoculated intracerebrally?

A

~1

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19
Q

How many attenuated la crosse virus mutant is needed to kill 50% of adult mice when inoculated intracerebrally?

A

> 10^6

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20
Q

How many attenuated la crosse virus mutant is needed to kill 50% of adult mice when inoculated subcutaneously?

A

> 10^7

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21
Q

What is the major goal of virology?

A

To determine viral and host genes that determine virulence

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22
Q

How are virulence genes usually identified?

A

They are identified by mutation, a virus that causes reduced or no disease in a specified system

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23
Q

What are the effects of viral virulence genes?

A

Viral replication
Invasiveness
Tropism
Modify the host defense systems
Enable the virus to spread in the host
Intrinsic cell killing effects

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24
Q

How does a virus with a mutation in gene required for virulence reproduce in a cell culture?

A

They reproduce well

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25
Q

How does a virus with a mutation in gene required for virulence reproduce in mouse brain?

A

Poor replication

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26
Q

Examples of virulence determinants that do not encode proteins

A
  1. Poliovirus - Attenuated sabin vaccine strains - Mutation in the 5’ NC region - Reducing neurovirulence
  2. Mengovirus - Deletion in the long poly(C) tract in the 5’ NC region - Reducing virulence
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27
Q

What are the different virus gene products that modify the host immune system?

A
  1. Autophagy and apoptosis
  2. Virokines and viroreceptors
  3. Modifiers of MHC-I and MHC-II pathways
  4. Complement binding proteins
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28
Q

What is the mechanism of rotavirus induced diarrhea?

A

During rotavirus reproduction in intestinal epithelial cells, it produces nsP4, which serves as nonstructural glycoprotein and viral enterotoxin, which inhibits the sodium-glucose luminal cotransporter, required for water reabsorption in the intestine. It also induces a PLC dependent calcium signaling pathway; increased intracellular calcium induce calcium dependent chloride secretion

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29
Q

Example of a cellular virulence factor

A

Trim5alpha

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30
Q

What does trim5alpha do?

A

Work on the viral capsid, prevents HIV-1 in old world monkeys, virions can enter but encounter block before reverse transcription

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31
Q

What is the name of anti-mir-122?

A

Miravirsen

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32
Q

What does miravirsen do in chimpanzees?

A

Reduce the yield of HCV

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33
Q

What is mir-122?

A

A liver specific miRNA necessary for HCV replication, which binds to its 5’-UTR

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34
Q

What are the mechanisms of cell injury by viruses

A

Cytolytic viruses: Cytopathic effects
Formation of syncytium: Enveloped viruses (Parainfluenza, HIV)
Apoptosis, necrosis, pyroptosis (a type of cell death primarily seen in inflammatory cells such as macrophages)
Viral inhibition of host protein and RNA synthesis; loss of membrane integrity, leakage of enzymes from lysosomes, cytoplasmic degradation

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35
Q

What is pyroptosis

A

Type of cell death primarily seen in inflammatory cells such as macrophages

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36
Q

Which viruses form syncytium

A

Enveloped viruses (HIV, influenza)

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37
Q

Mechanisms of global immune response suppression

A
  1. Replication in one or more cells of immune system
  2. Perturbation of cytokine homeostasis and intracellular signaling
  3. Viral proteins acting as virokines and viroreceptors (immune modulators)
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38
Q

What cells are infected in measles infection?

A

DC, monocytes, thymic epithelial cells

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39
Q

How does measles manifest itself?

A

Reduced delayed type hypersensitivity, enhanced infection

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40
Q

What cells are infected in rubella?

A

Lymphoid cells

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41
Q

How does rubella manifest itself?

A

Persistent rubella infection

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42
Q

What cells are infected in AIDS?

A

CD4+ T cells, monocytes

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43
Q

How does HIV manifest itself?

A

Neoplasia, opportunistic infection

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44
Q

Example of a host gene that controls host susceptibility to virus

A

flv

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45
Q

What does the flv gene encode?

A

2’-5’-oligo(A) synthetase

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46
Q

Which virus does flv gene determine susceptibility to?

A

flavivirus

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47
Q

What is the flavivirus susceptible mice strain named, and why is it susceptible?

A

C3H/He; has a mutated flv gene, 100% dead

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48
Q

What is the flavivirus resistant mice strain named? Survival percentage?

A

C3H/RV, 50% dead and 50% alive

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49
Q

What mutation protects from HIV-1 infection?

A

Ccr-5 delta32 mutation

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50
Q

In what percentage of people of European descent is Ccr-5 delta32 mutation present?

A

4-16%

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51
Q

How was a German AIDS patient cured?

A

With stem cell therapy with Ccr5 delta32 mutation

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52
Q

Full form of GWAS

A

Genome wide association studies

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53
Q

What are some SNPS that predispose human carriers to HSV encephalitis?

A

UNC-93B, TLR3, TRIF, TRAF3

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54
Q

Abbreviation: TRIF

A

TIR-domain-containing-adapter-inducing Interferon beta

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55
Q

Abbreviation: TRAF3

A

TNF receptor associated factor 3

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56
Q

What viruses does IFITM inhibit

A

Influenza, HCV, ebola, dengue

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57
Q

Abbreviation: IFITM

A

Interferon induced transmembrane protein

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58
Q

Which IFITM protein controls influenza morbidity and mortality in mice?

A

IFITM3

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59
Q

What mutation does humans hospitalized with severe influenza have?

A

Enriched in IFITM3 gene mutations

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60
Q

Which mouse MHC allele has more % splenomegaly?

A

H-2a/a

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61
Q

Which mouse MHC allele has less % splenomegaly?

A

H-2a/b

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62
Q

What are elite controllers also known as?

A

Long-term non-progressors

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63
Q

What is understood by long term non-progressors?

A

Low HIV loads without anti retro-viral therapy

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64
Q

What is the reason for elite controllers?

A

Multiple traits responsible

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65
Q

Which MHC allele is associated with elite controllers?

A

Specific MHC-I allele (HLA-B57)

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66
Q

Examples of two viruses that co-infect?

A

HIV-1 and HSV-2

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67
Q

What does HSV-2 stimulate production of?

A

Antimicrobial peptides

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68
Q

What antimicrobial peptide enhances HIV infection of Langerhans cells?

A

LL-37 by epithelial cells

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69
Q

Mechanism of action of LL-37 to enhance HIV infection?

A

Upregulates the HIV-1 receptors CD4 and CCR5

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70
Q

What happens when LCM (lymphocytic choriomeningitis) is injected intracerebrally of adult mice?

A

It is lethal

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71
Q

What happens when LCM (lymphocytic choriomeningitis) is injected intracerebrally of infant mice?

A

It survives (T cell response)

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72
Q

Why are old people more susceptible to infections?

A

Less elastic alveoli
Weaker respiratory muscles
Diminished cough reflex

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73
Q

Why are young people more susceptible to infections?

A

Immaturity of immune response

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74
Q

What does immaturity of immune response also lead to

A

Greater freedom from immunopathology

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75
Q

Which viruses are milder at young age?

A

Poliovirus, measles virus, mumps virus

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76
Q

Why are some some viruses milder at young age?

A

Better balance between protective and pathogenic immune response

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76
Q

Why is measles 300x more lethal in developing countries than Europe, N. America?

A

Because of malnutrition, which leads to compromised physical barriers and immune response

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77
Q

Why was 1918 influenza pandemic lethal for young adults as well?

A

Lacked protective immunity which would be conferred by previous infection with related virus

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78
Q

Which viruses are more lethal in pregnancy?

A

Hepatitis A,B,E, influenza

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79
Q

Which virus is more common in pregnancy?

A

Poliovirus

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80
Q

What are the factors other than viral or host determinants that influence viral infections?

A
  1. Cigarette smoking
  2. Air pollution
  3. Stress
  4. Malnutrition
  5. Pregnancy
  6. Age
  7. Male > Female
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81
Q

What are the different patterns of infection?

A
  1. Acute infection
  2. Persistent infection, smoldering
  3. Persistent infection, latent
  4. Persistent infection, slow
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82
Q

Example of a virus causing latent persistent infection?

A

HSV

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83
Q

Example of viruses causing slow persistent infection?

A

HIV
HTLV
Measles virus, SSPE

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84
Q

Example of a virus causing smoldering persistent infection

A

Lymphocytic choriomeningitis virus

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85
Q

Examples of viruses causing acute infections?

A

Influenza virus
Rotavirus
Rhinovirus

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86
Q

Course of a typical acute infection (Graph explanation)

A

X axis: Duration of infection
Y axis: Virus growth
Set a threshold level of virus required to activate adaptive immune response
Until establishment of adaptive immune response:
1. Innate defenses
2. Establishment of infection
Then:
Adaptive response
Memory
Graph two ends, entry of virus, virus cleared

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87
Q

What is an incubation period?

A

Initial period before obvious symptoms of disease, where virus is replicating, host is responding with cytokines of global effects, transmission of virus is possible

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88
Q

What does short incubation period imply?

A

Replication at primary site produces symptoms

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89
Q

What does long incubation period imply?

A

Symptoms beyond the primary site

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90
Q

What is the incubation pereiod of HepB and HepC?

A

50-150 days

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91
Q

Why are acute infections difficult/common public health problems?

A
  1. By the time we feel ill, infection may be over
  2. Serious endemics affecting millions each year (Influenza, measles, polio)
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92
Q

What are some viruses that can cause acute infections?

A

Influenza, polio, measles, rotavirus, norovirus, west nile virus

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93
Q

Which of influenza A,B,C cause pandemics?

A

A

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94
Q

Which of influenza A,B,C are mostly inapparent or cause mild upper respiratory tract illness?

A

C

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95
Q

Which of influenza viruses cause similar disease?

A

A,B

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96
Q

What is the hallmark of the influenza virus helping it evade immune system?

A

Antigenic variation

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97
Q

Methods of influenza transmission

A
  1. Droplets produced by coughing, sneezing, talking
  2. Direct contact with infected individuals
  3. Contact with contaminated surface, touch mouth, eyes, nose
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98
Q

Uncomplicated influenza series of actions

A
  1. Incubation period (1-5 days) depending on dose and host immune system
  2. Abrupt onset: Headache, chills, dry cough
  3. High fever, myalgias, malaise, anorexia
  4. Fever peaks within 24 hours: 38 - 40 degrees celsius
  5. Declines in 2-3 days
  6. Fever gone in 6 days
  7. Respiratory signs intensify with declining fever
  8. Dry cough becomes productive cough
  9. Cough, weakness persist 1-2 weeks
  10. Virus replicates throughout the tract, depending on sialic acid receptors for the strains
  11. Symptoms differ in elderly and children
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99
Q

What is the problem of diagnosing influenza with rapid lab tests?

A

Poor accuracy

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100
Q

Ways to diagnose influenza

A

PCR, viral culture, serology
influenza like illness (Ili)
Fever at least 100 degree farenheit
Cough or sore throat
No other known cause

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101
Q

What is reye syndrome?

A

Swelling in the liver and brain

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102
Q

What are the complications on influenza?

A

Primary viral pneumonia
Secondary bacterial pneumonia
Myositis (Generalized muscle pain)
Reye syndrome
Cardiac involvement

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103
Q

What is generalized muscle pain called

A

Myositis

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104
Q
A
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104
Q

What are the interventions of influenza?

A

Non-pharmaceutical
Vaccines
Antiviral drugs:
1. Oseltamivir (Tamiflu)
2. Zanamavir (Relenza)
3. Rimantadine (Flumadine)

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104
Q

How many episodes of diarrheal incidence each day

A

4.7 million

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105
Q

Reduction in diarrheal deaths for aged <5 years since 1980s

A

89%

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106
Q

Which enteropathogen is mostly associated with diarrheal deaths for children aged 0-59 m and to what percent

A

Rotavirus (28%)

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107
Q

Top 3 enteropathogens associated with diarrheal deaths of 0-59 months

A

Rotavirus (28%)
EPEC (11%)
Norovirus (10%)

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108
Q

Which viral agent was first shown to cause gastroenteritis?

A

Norovirus

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109
Q

Using what technique was norovirus first visualized in 1972?

A

Immunoelectron microscopy

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110
Q

When was the outbreak that got 50% of the students in Ohio affected by gastroenteritis

A

1968

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111
Q

Why is norovirus perfect human pathogen?

A
  1. Highly contagious >= 18 virus particles
  2. Rapidly and prolifically shed
  3. Virus evolution
  4. Aerosol transmission
  5. Evoking limited immunity
  6. Moderately virulent
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112
Q

What family is norovirus part of?

A

Calciviridae

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113
Q

Structure, genome and size of calciviridae

A

+SSRNA
Nonenveloped
7.6 kb

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114
Q

Which genogroups of norovirus affect humans?

A

GI and GII

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115
Q

Which GII genotype is mostly associated with humans?

A

GII.4

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116
Q

How do the genogroups of norovirus range?

A

7 groups GI, GII, GIII, GIV, GV, GVI, GVII

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117
Q

How many genotypes of norovirus are there?

A

~40

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118
Q

Which genogroup of norovirus is present in humans to a limited extent?

A

GIV

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119
Q

Can norovirus be present without diarrhea?

A

Yes in all ages

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120
Q

What are the settings of norovirus outbreaks

A

Cruise ships
Healthcare facilities
Schools
Leisure settings/hotels

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121
Q

Where do noroviruses bind?

A

Carbohydrates known as human blood group antigens, HbGAs

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122
Q

Who are less likely to be infected by norovirus?

A

Non-secretors

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123
Q

Which gut bacteria help norovirus?

A

HBGA+ to help cross gut-lining?

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124
Q

Where is rs601338 found?

A

Chromosome 19 in the alpha (1,2) fucosyltransferase FUT2 gene

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125
Q

Which is the inactive non-secretor RS601338 allele?

A

Homozygous A:A, resistant to norovirus

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126
Q

Which RS601338 alleles are susceptible to norovirus infection?

A

A:G, G:G

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127
Q

Why are non secretors less likely to have norovirus?

A

They do not have carbohydrate HBGAs in their gut linings for norovirus to bind

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128
Q

What are the norovirus antiviral targets?

A

Blood group trisaccharide A (alpha-galnac, beta-gal)
Blood group trisaccharide B

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129
Q

Factors making norovirus vaccine development challenging

A
  1. Unknown duration of protective immunity
  2. Unknown effects of pre-exposure history
  3. Few human studies
  4. Lack of appropriate model systems
  5. Antigenic variation within some genotypes
  6. Antigenic variation among genogroups and genotypes
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130
Q

How many genotypes in genogroup I of norovirus?

A

9

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131
Q

What is the disease burden of genogroup I for norovirus?

A

~10%

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132
Q

How many genotypes in genogroup II of norovirus?

A

22

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133
Q

What is the disease burden of genogroup II for norovirus?

A

70% : GII.4
10% : Other GII genotypes

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134
Q

What is the benefit of multivalent vaccine?

A

Broadens protection against genotypes not included in the vaccine

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135
Q

What is the norovirus vaccine?

A

Multivalent VLP vaccine

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136
Q

When to move to vaccine reformulation for norovirus?

A

Changes in GII.4 antigenicity
Changes in epidemiologically important strains

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137
Q

Most common cause of childhood gastroenteritis

A

Rotavirus

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138
Q

What percentage of all mortality <5 years does rotavirus diarrheal dehydration cause in developing world

A

~5%

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139
Q

What is the condition of rotavirus in US?

A

Prevaccine: 1 in 72 hospitalized, all children infected by 5 years

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140
Q

How many physician visits does rotavirus cause per year

A

25000000

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141
Q

How many hospitalizations does rotavirus cause per year

A

2000000

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142
Q

How many deaths does rotavirus cause per year

A

800000

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143
Q

Common features of rotavirus pathogenesis

A
  1. Transmitted by fecal oral transmission
  2. 10^8-10^10 particles/ml of feces
  3. 10-100 virions
  4. Infants <24 months risk of dehydration
  5. Older children or reinfected adults, mild or no disease
  6. Contaminated hands
  7. Contaminated food
  8. Virions are stable in environmental surfaces
  9. Recovery complete unless electrolyte replenishment not done
  10. Incubation period 1-3 days
  11. Asymptomatic infections play a role in spread
  12. Vomiting; 4-8 days of diarrhea, fever
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144
Q

What kind of vaccine is rotarix?

A

Infectious attenuated human isolate (Rotavirus)

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145
Q

What kind of vaccine is RotaTeq?

A

Human-bovine reassortant (Rotavirus)

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146
Q

Acute vs persistent infections

A

Acute - Rapid + Self - limiting
Persistent - Long term, life of host
Stable, characteristic for each virus family
Most persistent infections probably begin as an acute infection

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147
Q

What are persistent infections

A

Occur when primary infection is not cleared by immune response; viral genome, virions, proteins continue to be produced; viral immune modulation; occurs when cytopathic effects are absent, or host defenses are reduced, viral genomes may remain after proteins are not detected, no single mechanism

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148
Q

Give five examples of viruses which cause persistence infection.

A

HTLV
HIV
Hepatitis B, Hepatitis C
HSVI, HSVII
Adenovirus
Polyomavirus
Papillomavirus
Measles virus
EBV

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149
Q

Hepatitis B virus: site of persistence

A

Liver, lymphocytes

150
Q

Hepatitis C virus: site of persistence

151
Q

Hepatitis B and C virus persistence consequence

A

Cirrhosis, hepatocellular carcinoma

152
Q

Example of a virus infecting cells of the immune system, and what do they infect

A

HIV: Macrophages, monocytes, dendritic cells, CD4+ T cells

153
Q

Acute HBV infection characteristics

A
  1. Main target hepatocytes
  2. 95% adults, 5-10% newborns, resolve acute infections
  3. Transmitted by exposure to blood (Transmission, nosocomial, sex, child birth, drug use)
154
Q

What are the characteristics of persistent/chronic hepatitis B virus infections?

A
  1. Hepatocellular carcinoma
  2. ~350 million worldwide have chronic HBV
  3. Virus is not cytopathic for hepatocytes
  4. Cytopathic T lymphocytes kill infected cells
  5. Fibrosis > Cirrhosis > liver failure
  6. Hepatocellular carcinoma develops after 20-30 years after asymptomatic or chronic infection
155
Q

Which antibody is not made in chronic infections of hepatitis B infection?

A

Anti-HBs
Anti-HBe

156
Q

Which antibodies are made in both acute and chronic infections?

A

IGM anti-HBc
Total anti-HBc

157
Q

Which antibodies are made specifically in acute HBV?

158
Q

Which of the measures do not come down in chronic infections of HBV?

A

ALT in blood
HBsAG
HBV-DNA

159
Q

What does serological testing of hepatitis B involve?

A

Measurement of HBV specific antigens or antibodies (Different serological markers or combination of markers)

160
Q

Significance of anti-HBs

A
  1. Successful vaccination against Hepatitis B
  2. Person has been recovered and immune from hepatitis B virus infection
161
Q

Significance of anti-HBc (Core antibody)

A
  1. Previous or ongoing HBV infection in an undefined timeframe (persists for life), onset of symptoms in acute HBV
162
Q

Significance of IgM antibody to HBc

A

Recent infection (<6 months). Presence = Acute infection

163
Q

HBsAg - Negative
anti-HBc - Positive
anti - HBs - Negative

interpretation

A

Resolved infection (Most common)
Resolving acute infection
False positive anti HBc, susceptibe
“Low level” chronic infection

164
Q

HBsAg - Positive
anti-HBc - Positive
IgM anti-HBc - Negative
anti-HBs - Negative

A

Chronic infection

165
Q

HBsAg - Positive
anti-HBc - Positive
IgM anti-HBc - Positive
anti-HBs - Negative

A

Acutely infected

166
Q

HBsAg - Negative
anti-HBc - Negative
anti-HBs - Positive

A

Immune from vaccination

167
Q

HBsAg - Negative
anti-HBc - Positive
anti-HBs - Positive

A

Immune due to natural infection

168
Q

HBsAg - Negative
anti-HBc - Negative
anti-HBs - Negative

A

Susceptible

169
Q

Hepatitis C virus genome type

170
Q

Hepatitis C virus family

A

Flaviviridae

171
Q

How many people worldwide and what percentage of population are infected with HCV?

A

185 million (2.2% of population)

172
Q

What happens in acute HCV infection

A

Typical hepatitis signs or asymptomatic

173
Q

What happens in chronic HCV infection

A

High level viremia

174
Q

Hepatitis C chronic infection flowchart

A

Acute infection ->
i. Spontaneous resolution
ii. 60-85% chronic infection

Chronic ->
i. Stable
ii. Cirrhosis in 5-20% of infected in 25 years of infection

Cirrhosis ->
i. Slowly progressive
ii. Decompensation hepatocellular carcinoma (~7% per year)

175
Q

How many genotypes of hepatitis C virus

176
Q

What are the genotypes of HCV based on

A

Genomic variation

177
Q

How many subtypes does hepatitis C virus have

178
Q

When was HCV first identified

179
Q

What are the treatment for HCV infections?

A

Past-decade:
Pegylated interferon combined with ribavirin
Past 5 years:
Interferon-free direct acting antiviral (DAA)

180
Q

Cons of pegylated interferon combined with ribavirin

A

Suboptimal response rates (54-56%)
Significant toxicity

181
Q

Interferon-free direct acting antiviral (DAA) characteristics

A

Effectiveness >95%
Highly expensive
Short treatment course
Licensed in 2014

182
Q

When was DAA licensed

183
Q

What are the different HCV genotypes? Why are they important?

A

1-6
Help determine the appropriate medication for chronic HCV

184
Q

Which interferon free regimens are effective against all genotypes of HCV?

A

Sofosbuvir + declatasvir (+- RBV)

185
Q

In what class of people was highest prevalence of HCV observed in Bangladesh?

A

PWID (people who inject drugs), >50% in some cities including Dhaka

186
Q

What is the general prevalence of HCV in Bangladesh

A

0.2 - 0.9%

187
Q

Prevalence of HCV in Bangladeshi blood donors

188
Q

What are the general properties of latent infection?

A
  1. Viral gene products that promote productive replication are not made or found in low concentration
  2. Cells harboring the latent viral genome are poorly recognized by the immune system
  3. Viral genome persists intact so that productive infection can be initiated to spread infection to new hosts
189
Q

Process of transformation

A

Hamster embryo -> Use trypsin to make single cells -> seed plates -> Chemically treat -> Transformed clones morphologically identified

190
Q

What are the properties of transformed cells

A

Immortal: grow indefinitely (HeLa cells)
Loss of contact inhibition
Loss of anchorage dependence
Colony formation in semi-solid media
Decreased requirements for growth factors (serum)

191
Q

What is cancer? Why does it develop?

A

A malignant tumor, a genetic disease.
Growth that is not encapsulated and infiltrates into surrounding tissues; replacing normal tissues

192
Q

What do the mutations related to cancer affect?

A

Steps in cell communication, growth, proliferation

193
Q

What are the sources of mutation in cancer?

A

Inherited
Caused by DNA damage
Environmental carcinogens
Infectious agents including viruses

194
Q

Benefit of studying virus transformed cells?

A

Provides insight into molecular events that establish oncogenic potential

195
Q

Give examples of five viruses and their associated cancer.

A

Adenoviridae - Various solid tumors
Polyomaviridae - Various solid tumors
Hepatitis C virus (Flaviviridae) - Hepatocellular carcinoma
Hepadnaviridae - Hepatocellular carcinoma
Papillomaviridae - Papillomas and carcinomas
Poxviridae - Myxomas and fibromas
Herpesviridae - Carcinoma, sarcoma, lymphoma
Retroviridae - Hematopoietic cancers, sarcoma, carcinoma

196
Q

What percentage of human cancers have relation with viruses

197
Q

Do viruses need to cause transformation and oncogenesis to replicate?

198
Q

Which scientist indicated the idea that virus infection can cause cancer?

A

Dr. Peyton Rous

199
Q

When did Dr. Peyton Rous removed a tumor from an english hen and injected cell-free filtrate from the tumor into a healthy chicken which developed the tumor?

A

Oct 1, 1909

200
Q

When did Dr Peyton Rous get his nobel prize in physiology and medicine

201
Q

Which virus did he discover to cause cancer?

202
Q

How many nobel prizes did RSV give rise to

203
Q

How many feuding camps were the cancer researchers split in 1950s and what were they?

A
  1. Led by Rous: Viruses cause cancer, no such virus found in human studies
  2. Epidemiologists said exogenous chemicals, no mechanistic explanation
  3. Genes internal to the cell, weak circumstantial evidence
204
Q

Examples of viral transformation of cells

A

Most infected cells die, but rare cells do not, are transformed

i.e.
1962: Rare BHK21: Polyoma: Changed shape, kept growing
1964: Swiss 3T3 cells: SV40: Rare cells grew as colonies

205
Q

How can a viral infection transform a cell?

A
  1. Cytopathic effects must be reduced or eliminated so the infected cell does not die
  2. Viral replication must be reduced or eliminated so the transformed cell does not produce virions
  3. The cell must continue to divide so that it becomes immortal
206
Q

What happens to the viral genome
in transformed cells?

A
  1. Some transformed cells contain all or parts of viral genomes integrated into the host genome
  2. Sometimes no viral nucleic acid remain in the transformed cell
  3. Key, but mystifying early observations
207
Q

Who discovered Avian Leucosis Retroviruses ALV and when?

A

1908, Ellerman and Bang

208
Q

What virus is most chickens infected with within a few months of hatching?

A

Avian Leucosis Retrovirus

209
Q

What percentage of ALV infected chickens develop leukemia and what age

A

3%, >14 weeks

210
Q

What happens to 97% of ALV infected chickens

A

Develop transient viremia, not leukemia, become immune

211
Q

What does the leukemia lead to in ALV infected chickens when they age?

A

Connective tissue tumors or sarcoma (solid tumor)

212
Q

What happens if virus isolated from solid tumors that are derived from leukemia is inserted into a healthy chicken?

A

Solid tumors

213
Q

Example of a virus isolated from solid tumors that are derived from leukemia. What is their state mostly?

A

Rous Sarcoma Virus
Defective, cannot replicate independently

214
Q

What was different about the viral genomes isolated from solid tumors from that of ALV that allowed them to form solid tumors but not ALV?

A

A piece of the ALV genome was replaced with the host DNA (oncogene) named v-SRC (recombination)

215
Q

Which gene allows rous sarcoma virus to form solid tumors but not ALV?

216
Q

Who identified the oncogene v-SRC and when?

A

J. Michael Bishop and H. Varmus, 1976

217
Q

When did J. Michael Bishop and H. Varmus gain nobel prize for their discovery of v-SRC

218
Q

What happens to ALV infected chickens if you let them age?

A

They develop rare tumors, each time with retroviruses derived from ALV, but each different, and most defective

219
Q

The retrovirus genomes isolated from each new solid tumor

A

had different host DNA, NOT the v
–‐SRC gene found in RSV

220
Q

What are the structures of typical progenitors of avian transducing retroviruses and mammalian transducing retroviruses?

A

Avian leukosis virus: gag, pol, env
Murine leukemia virus: gag, pol, env

221
Q

Defective vs non-defective virus

A

Defective viruses require helper viruses to produce more virus
Usually missing envelope proteins
Envelope genes deleted during oncogene capture
PRC II avian sarcoma virus require avian leucosis virus as helper, due to gene fps

222
Q

How many proto-oncogenes are identified

223
Q

How does the nomenclature of proto-oncogenes go

A

Normally cellular genes are abbreviated with a c in front of the name, i.e., c-ONCS, c-SRC, c-MYC, c-MOS, c-RAS

224
Q

Altered copies of c–ONCS isolated from retroviruses of tumors are named like

A

v-ONCS, v-RC, v-MYC, v-MOS, v-RAS

225
Q

Who discovered the first oncogenic DNA virus and when?

A

Richard Shope, 1933

226
Q

Which was the first oncogenic DNA virus discovered?

A

Papillomavirus that caused warts or papillomas in cottontail rabbits

227
Q

Who discovered murine polyomaviruses and when?

A

Ludwig Gross, 1953

228
Q

What is the natural host of polyomavirus and what does it do under certain conditions?

A

Mouse, cause rare tumors under certain conditions

229
Q

How is polyomavirus in mouse

A

Ubiquitious, no role in mouse cancer

230
Q

Where does polyomavirus cause tumors

A

Tumors of many tissues (polyomas) in infant hamsters, rats, rabbits

231
Q

What did Eddy and Hilleman show in 1962?

A

They showed that SV40, a contaminant of early poliovirus vaccines, induced rare tumors in newborn hamsters

232
Q

Which virus was early poliovirus vaccines contaminated by

233
Q

What is the natural host of SV40

234
Q

SV40 transforms monkey cell in culture, True or False?

235
Q

In which animal does SV40 cause cancer?

A

Rats and hamsters

236
Q

SV40 in mouse

A

Non-permissive

237
Q

SV40 in monkey

A

Permissive

238
Q

Mouse polyomavirus in mouse

A

Permissive

239
Q

Mouse polyomavirus in monkey

A

Non-permissive

240
Q

What is the rate of polyomaviral transformation of cultured cells

A

1 in 100,000

241
Q

Does adenovirus cause tumors and transformation of cultured cells?

A

Very rare events like polyomavirus and papillomavirus

242
Q

Does adenovirus cause cancer in humans

A

No despite many human serotypes

243
Q

How many tumors does adenovirus add in hamsters?

A

12-18 tumors
7-11 poorly tumorigenic

244
Q

What are the properties of T antigens?

A
  1. Required for replication
  2. Activate viral transcription
  3. Required for viral DNA synthesis
  4. They are the only viral genes always retained in tumor cells or transformed cells
  5. Can alone transform cultured cells
  6. They are encoded by essential viral genes
245
Q

T antigens found in SV40

A

Large T, small T

246
Q

T antigens found in polyomavirus

A

Large T, middle T, small T

247
Q

Papillomavirus T antigen encoded by

A

E5, E6, E7 genes

248
Q

T antigens found in adenovirus

249
Q

What are the three cellular proteins that are involved with T antigen to produce transformed cells?

A
  1. p53 (53 kDa cell protein) binding SV40 T antigen
  2. Retinoblastoma protein (Rb) binding E2F
  3. Transcription of a set of adenovirus early genes (E2 gene cluster) require E2F cell proteins
250
Q

Why is transformation rare?

A

It requires two low probability events to occur simultaneously.
1. Lethal late genes must not be expressed
I. Rare spontaneous deletion of late genes must occur
II. Virus infects semi-permissive cells where late gene expression is blocked
2. T antigens must be on constitutively and transmitted to every cell
i. Viral DNA encoding T antigen must be incorporated in host DNA
ii. T antigen must be produced

251
Q

What is the proven best defense against viruses?

252
Q

How are vaccines the proven best defense against viruses?

A

They mobilize the host immune system to prevent virus infection (immune memory).

They break the chain of transmission

253
Q

Who developed the first vaccine that we know of and when

A

Edward Jenner, 1796; smallpox

254
Q

What vaccine did Pasteur develop and when

A

Rabies vaccine, second vaccine developed; 1885

255
Q

Who introduced the term vaccination and what was its origin

A

Pasteur, vaccination from vacca (Latin, cow) in honor of Jenner

256
Q

When was yellow fever, influenza vaccines developed

257
Q

Name two viruses that underwent large scale vaccination campaigns

A

Polio, measles

258
Q

Inactivated vaccine vs oral vaccine for polio

A

Oral more effective

259
Q

Why are many childhood diseases rare?

A

Because of immunization

260
Q

What is a major part of the first world’s public health measure, but not the third world’s

261
Q

How does vaccination work in the real world?

A

They work via Herd immunity: Maintenance of a critical level of immunity in the population

262
Q

What does herd immunity imply?

A

Virus spread stops when the probability of infection drops below a critical threshold

263
Q

What does the critical threshold in herd immunity depend on?

A

It depends on the virus and the population

264
Q

What percentage of the population needs to be immunized to get herd immunity for smallpox

265
Q

What percentage of the population needs to be immunized to get herd immunity for measles

266
Q

What percentage of population is immune from measles when 80% is immunized with measles vaccines?

267
Q

How to make a vaccine?

A
  1. Induction of an appropriate immune response (Th1 or Th2)
  2. Vaccinated individuals must be protected against disease caused by the virulent form of the specific pathogen.
    Just getting a response isn’t enough (producing antibodies)
268
Q

What are active and passive vaccination?

A

Active: Long term protection (Instilling into the recipient a modified form of the pathogen or material derived from it that induces immunity to disease)
Passive: Short term protection (Instilling the products of the immune response [Antibodies or immune cells] into the recipient

269
Q

What are the requirements of an effective vaccine?

A
  1. Safety: no disease, minimal side effects
  2. Induce protective immunity in the population
  3. Protection must be long-lasting
  4. Low cost (<1 dollars, WHO), genetic stability, storage considerations, delivery (oral vs needle)
270
Q

What are the five stages of vaccine development?

A
  1. Preclinical (Lab studies animals) : Number of doses, local application, immune response
  2. Phase I (Tens healthy adults): Safety, minimizing adverse effects, potential risks
  3. Phase IIa (Hundreds target people): Side effects, immunogenicity
  4. Phase IIb/III (Thousands target people): Effectiveness, immunogenicity
  5. Phase IV (Hundreds of thousands): Safety monitoring, potential adverse effects
271
Q

What are the types of coronavirus vaccines?

A
  1. DNA/RNA
  2. Protein subunit
  3. Viral vector
  4. Live attenuated
  5. Inactivated
272
Q

How do DNA/RNA vaccines work?

A

Uses DNA or RNA molecules to teach the immune system to target key viral proteins

273
Q

Example of DNA coronavirus vaccine?

274
Q

Advantages of DNA/RNA vaccine?

A

Easy and quick to design

275
Q

What is live-attenuated vaccine?

A

Uses a weakened version of the actual virus

276
Q

What is inactivated vaccine?

A

Uses the whole virus after it has been killed with heat or chemicals

277
Q

What is a subunit vaccine?

A

Uses a piece of a virus’s surface to focus our immune system to a single target

278
Q

What is a viral vector vaccine?

A

This approach takes a harmless virus and uses it to deliver viral genes to build immunity

279
Q

What is the advantage of using viral vector vaccine?

A

Live viruses tend to elicit stronger immune response than dead viruses or subunit vaccines

280
Q

Existing examples of viral vector vaccines

A

Ebola, veterinary vaccine

281
Q

Disadvantage of using viral vector vaccine

A

Important to pick a viral vector that is truly safe. An immune response to the viral vector could make the vaccine less effective.

282
Q

Group testing viral vector vaccine for Covid-19

A

Johnson and Johnson
University of Oxford and Astrazeneca
Cansino Biologics

283
Q

Advantage of using subunit vaccine

A

It focuses your immune response on the most important part of the virus for protection and it cannot cause infection

284
Q

Disadvantages of using subunit vaccine

A

It may not elicit a strong immune response and other chemicals may need to be added to boost long term immunity

285
Q

Existing examples of subunit vaccine

A

Pertussis
Hepatitis B
Human Papilloma Virus

286
Q

Existing examples of inactivated vaccine

A

Poliovirus

287
Q

Existing examples of live attenuated vaccine

A

Measles, mumps, rubella, chickenpox

288
Q

Advantage of using inactivated vaccine

A

Safe because virus is already dead and easy to make

289
Q

Advantage of using live attenuated vaccine

A

Stimulates a robust immune response without causing serious disease

290
Q

Disadvantages of using DNA/RNA vaccine

A

Never been done before. No licensed DNA or RNA vaccine currently in use.

291
Q

Disadvantages of using live attenuated vaccine

A

May not be safe for immunocompromised individuals

292
Q

Disadvantage of using inactivated vaccine

A

Not as affective as a live virus. Some previous inactivated vaccines have made the disease worse. Safety for the novel coronavirus needs to be shown in clinical trials.

293
Q

Group testing live attenuated vaccine for Covid-19

A

Codagenicx
Indian Immunologicals Ltd.

294
Q

Group testing inactivated vaccine for Covid-19

A

Sinovac
Sinopharm

295
Q

Group testing subunit vaccine for Covid-19

A

Novavax
AdaptVac

296
Q

How can we inactivate a virus?

A

Chemical procedures like formalin, nonionic detergent, beta-propriolactone

297
Q

What is the special feature of inactivated vaccines?

A

Infectivity is eliminated but antigenicity is not compromised

298
Q

What is an example of an inactivated vaccine?

A

Inactivated poliovirus vaccine IPV

299
Q

How was IPV made?

A

Treated with formalin to destroy infectivity

300
Q

History of IPV

A

1954: National Foundation for Infantile Paralysis sponsored clinical trials of Jonas Salk’s IPV, 1,800000 children

> 50% protection, results were released on 12 April, 1955, licensed the same day

Cutter incident: Wrongly inactivated virus, caused polio, many people died

301
Q

How many people die in the US per year for influenza?

A

3000-49000

302
Q

How are inactivated influenza vaccines made?

A

Virus grown in chicken embryonated eggs, formalin-inactivated or detergent or chemically disrupted virions.

Or vaccine produced in cell culture avoids egg allergies (flucelvax)

303
Q

How many doses of influenza inactivated vaccine are manufactured each year in the US?

A

75-100 million

304
Q

How effective is inactivated influenza vaccine?

A

60% effective in individuals <65 years

305
Q

What does the protection by inactivated influenza vaccine correlate to?

A

Correlates to serum antibodies to HA, NA

306
Q

How are subunit vaccines?

A

Could be recombinant or non-recombinant.

Non-recombinant:
Break the virus into components (fractionation), purify the components, and immunize with purified components

Recombinant:
Clone the viral gene encoding the desired antigen (which is usually a capsid or membrane protein), express the gene in bacteria, insect cells, cell culture, yeast, purify the protein and that would make the subunit vaccine

307
Q

What are the advantages of a modern subunit vaccine?

A

Recombinant DNA technology
No viral genome or infectious virus

308
Q

What are the disadvantages of a modern subunit vaccine?

A

Poor immunogenicity
Expensive
Injected

309
Q

How is HBV subunit vaccine produced?

A

HbsAg protein produced in yeast and they assemble into empty particles

310
Q

Which protein is targeted to make Human Papilloma virus subunit vaccine?

A

L1 major capsid protein

311
Q

Where is the gene for L1 major capsid protein inoculated for making subunit vaccine?

A

Recombinant yeast or baculovirus

312
Q

For what HPV types does Gardasil (Merck) make vaccines?

A

6,11,16,18

313
Q

For what HPV types does Cervarix (GlaxoSmithKline) make vaccines?

314
Q

Where are the Gardasil (Merck) HPV vaccines grown?

A

S. cerevisiae

315
Q

Where are the Cervarix (GlaxoSmithKline) vaccines grown?

A

Insect cells

316
Q

What are the common problems for inactivated and subunit vaccine?

A

Pure proteins often requires an adjuvant to mimic inflammatory effects of infection
They do not send danger signals to the immune response
Viral proteins don’t replicate or infect

317
Q

How do adjuvants produce a more robust acquired immune response with less antigen?

A

Stimulate inflammation
Slow release of antigen at the site of inoculation

318
Q

What can stimulate early processes in immune recognition?

319
Q

What kind of adjuvant is MF59?

A

Squalene water-in-oil emulsion (depot, innate stimulatory), Europe

320
Q

What kind of adjuvant is alum?

A

Aluminum hydroxide/Aluminum phosphate used in HBV, US

321
Q

What kind of adjuvant is AS04?

A

In cervarix
alum, monophosphoryl lipid A, TLR4 ligand, US

322
Q

How are live attenuated vaccines made?

A

Virus replicates, stimulates immune response
Infection causes mild or inapparent disease

323
Q

The graph for the live vs killed vaccine; features of killed vaccine

A

Three doses

324
Q

The graph for the live vs killed vaccine; features of live vaccine

A

Initial dose, amplification of injected dose

325
Q

What was mRNA technology originally developed as?

A

Cancer therapy

326
Q

How the Pfizer-BioNTech vaccine works?

A
  1. Scientists take the genetic sequence of the spike protein and synthesize an mRNA sequence, instructions that the cells can use to produce spike protein
  2. Synthetic mRNA is packaged in a lipid nanoparticle that delivers the instructions into the cell
  3. Once inside the cell, the cellular machinery follows the instructions to produce the viral protein, displayed on the surface of the cell and stimulates an immune system response
327
Q

Which among the DNA and RNA vaccines manufacturing require cells or animal substrates

328
Q

Amplification (Number of protein antigen molecules per molecule of mRNA delivered) ranking for live attenuated vaccines, DNA vaccines, RNA vaccines, protein subunits or inactivated vaccines

A

Live attenuated > plasmid DNA > mRNA > protein subunits/inactivated

329
Q

How is the immuno-stimulatory effects of plasmid DNA compared to mRNA vaccines?

A

Fewer and better defined

330
Q

Regulatory concerns of integration of RNA vaccines

A

theoretically should not integrate if no endogenous retroviruses or retroviruses due to infection are present

331
Q

Which among DNA and RNA virus vaccines need to enter the nucleus

332
Q

How can immunostimulatory effects decrease potency of mRNA

A

Decreased stability of mRNA
Decreased translation into protein
Effects upon desired type of immunity

333
Q

Why is formulation needed for mRNA vaccine?

A

This observation is based upon the use of formulations by the majority of mRNA entities in clinical trials

334
Q

Why may finding the optimal formulation/ delivery device be challenging for humans?

A

Unpredictability of animal models

335
Q

What is known to cause toxicity in RNA based drugs?

A

Unnatural modified nucleoside analogues

336
Q

How can the concomitant administration of other drugs influence the potency of mRNA vaccine?

A

It may impact mRNA metabolism and thus decrease the potency

337
Q

Which vaccine would have a therapeutic effect after an individual is already infected?

338
Q

What is our second arm of antiviral defense

A

Antivirals

339
Q

How long has antiviral research spanned and what is the number of antivirals available in the US market

A

50 years
30 antivirals

340
Q

What are the maximum number of antivirals against

A

HIV and herpesviruses (persistent infections)

341
Q

Targets of antivirals for HIV infection

A

DNA polymerase
Reverse transcriptase

342
Q

Targets of antivirals for herpesvirus infection

A

DNA polymerase

343
Q

Targets of antivirals for influenza A infection

A

virion uncoating
viral neuraminidase

344
Q

Targets of antivirals for influenza B infection

A

viral neuraminidase

345
Q

Targets of antivirals for hepatitis C virus infection

A

Inosine monophosphate dehydrogenase

346
Q

Targets of antivirals for respiratory syncytial virus (RSV) infection

A

Inosine monophosphate dehydrogenase

347
Q

Why are there so few antiviral drugs?

A
  1. Compounds interfering with virus growth can adversely affect the host cell, as side effects are common which is unacceptable and every step in viral life cycle engages host functions
  2. Many medically important viruses cannot be propagated, have no animal models or are dangerous
    i.e., Lassa, smallpox, HBV, HPV, norovirus, ebola
  3. A compound must block the virus replication completely, has to be potent, that makes drug discovery expensive, as partial inhibition may give rise to resistant mutants
  4. Many acute infections are of short duration and thus by the time the patient feels ill, it is too late to impact clinical disease. The drugs in this case must be given early in infection or injected prophylactically to populations at risk, which gives rise to safety issues, and giving drugs to healthy people is not wise. Moreover, lack of rapid diagnostic reagents has hampered the development of antiviral drugs. No broad spectrum antiviral agents are currently available.
348
Q

Which medically important viruses cannot be propagated?

A

Smallpox, ebola, lassa, HPV, HBV, norovirus

349
Q

When did the first modest search for antiviral drugs occur?

A

Early 1950s

350
Q

What did the chemists target in the first modest search for antiviral drugs?

A

They looked at derivatives of sulfonamide antibiotics
Synthesis of thiosemicarbazones active against poxviruses

351
Q

When did the blind screening programs to find chemicals with antiviral activity begin?

A

1960s and 1970s

352
Q

How was the blind screening programs spurred on?

A

Successes in the treatment of bacterial infections with antibiotics

353
Q

What is blind screening for antiviral discovery?

A

No attempt to focus discovery on a virus or virus-specific mechanism

Random chemicals or natural product mixtures are tested for ability to block replication of a variety of viruses in cell culture systems

354
Q

What are hits in blind screening for antiviral discovery?

A

Compounds or mixtures that can block viral replication in-vitro, which are purified and fractions tested in various cell cultures and animal models for safety and efficacy

355
Q

What are leads in blind screening for antiviral discovery?

A

The compounds (hits) that are modified systematically by medicinal chemists to reduce toxicity, increase solubility, and bioavailability and to improve other pharmokinetic properties

356
Q

Which antiviral was approved in late 1960s for treatment of influenza A which is one of the three antivirals for the virus?

A

Symmetrel (amantadine)

357
Q

When was the mechanism of action of Symmetrel deduced?

358
Q

What are the strategies today for antiviral discovery?

A
  1. Blind screening procedures are dead
  2. Recombinant DNA technology and sophisticated chemistry make targeted discovery possible
  3. Modern technology allow inhibitors to be found even for viruses that cannot be propagated in cell cultures
  4. Life cycle of most viruses known, targets for intervention can be generalized
  5. Essential virus genes cloned, expressed in genetically tractable organisms, purified, and analyzed in atomic detail
359
Q

What are the main targets of antiviral drug discovery?

A

Influenza (NA inhibitor, entry inhibitor)
HIV (Fusion inhibitor, protease inhibitor, nucleoside-non-nucleoside analogs)
HCV (Protease inhibitor, interferon, nucleoside-non-nucleoside analog)
Herpesvirus (Nucleoside-non-nucleoside analog)

360
Q

How does symmetral (amantadine) work

A

It interacts with influenza virus M2 protein (ion channel) and blocks the entry of the protons into the virion and prevents uncoating

361
Q

How do inhibitors of NA (Oseltamivir-Tamiflu, Zanamivir- Relenza) work?

A

They are designed to mimic natural ligand (sialic acid), and the closer the inhibitor is to the natural ligand, the less likely the virus will mutate or change to avoid binding drug as it would lose its viable function

362
Q

Which among Tamiflu and Relenza more closely resemble sialic acid?

363
Q

What are the targets for intervention of HIV replication?

A

Virion assembly, release: Protease inhibitor
Cell attachment, fusion entry: CD4 derivatives, chemokine analog, SU/V3 loop inhibitors
Reverse transcription: Nucleoside analogs, nonnucleoside inhibitors
Integration: Integrase inhibitors
Transcription and post-transcriptional processing: Tat inhibitor

364
Q

AZT

A

Azido-deoxythymidine (First HIV drug) is a nucleoside analog drug which was initially discovered during screens for anti-tumor cell compounds, they are phosphorylated to active form by kinases, and works in chain termination, not good substrates for most cellular polymerases, better for HIV-1 RT. But, it has substantial side effects (unlike acyclovir). Half life is 1 hour (degraded by liver enzymes), it can be given orally, absorbed rapidly. Patients need 2-3x dose daily, multidose regime give rise to resistant mutants.

365
Q

NNRT1

A

Non-nucleoside HIV-1 RT inhibitors
It targets away from the active site, but it works in a way so the reverse transcriptase does not work

366
Q

What is an example of a HIV-1 protease inhibitor?

A

Peptidomimetic

367
Q

What is a key finding that helped in the development of HIV-1 protease inhibitor?

A

HIV protease recognizes and cleaves small synthetic petides

368
Q

Example of a CCR5 inhibitor

369
Q

Example of a HIV fusion inhibitor and when was it licensed

A

Fuzeon, March 2003

370
Q

What is the composition of HIV fusion inhibitor

A

36 aa synthetic peptide

371
Q

How does HIV fusion inhibitor work

A

It binds to the transmembrane subunit of viral glycoprotein and blocks the transition into fusion active conformation

372
Q

Problems with HIV fusion inhibitor

A

Resistance can grow by amino acid changes in the peptide binding site of the TM
Very expensive (25000 USD/yr)
Must be injected

373
Q

What is combination therapy?

A

It targets different mechanisms and one pill can contain three inhibitors
HAART: HIV can be treated as a chronic disease

374
Q

Pathological lesions graph:
Japanese encephalitis virus

A

C-100
B-100
S-80

375
Q

Pathological lesions graph:
Yellow fever virus 17D strain

A

C-82
B-72
S-42

376
Q

Pathological lesions graph:
West Nile Virus

A

C-75
B-95
S-40

377
Q

Pathological lesions graph:
Langat virus

A

C-100
B-60
S-30

378
Q

Pathological lesions graph:
Dengue virus

Virology (5 decks)

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