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Micro Exam 3 > Holland: RNA Viral Repiratory Tract Infections > Flashcards

Holland: RNA Viral Repiratory Tract Infections Flashcards

1
Q

Respiratory Tract Infections

Basics:

A
  • Most common form of infectious disease
  • ~80% of RTIs caused by viruses
  • Most respiratory infections remain localized, but some viruses can initially infect the respiratory tract and spread systemically
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2
Q

Respiratory Tract Infections

Modes of Transmission: (2)

A
  • Aerosolized infectious droplets

- Manual spread (direct contact or fomites)

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3
Q

Innate and Adaptive Immune Mechanisms of Protection of Respiratory Tract: (7)

A
  • Reduced temperature in URT
  • Mucous
  • Mucins
  • Ciliated cells
  • Toll-like receptors
  • Interferons
  • IgA (secreted immunoglobulins in mucous)
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4
Q

Innate and Adaptive Immune Mechanisms of Protection of Respiratory Tract
Mucins:

A

Decoy receptors (prevent bacteria from attaching to normal host cells)

High viscosity (difficult for pathogens to spread)

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5
Q

Innate and Adaptive Immune Mechanisms of Protection of Respiratory Tract

Ciliated cells:

A

Move mucous, clear particles

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6
Q

Innate and Adaptive Immune Mechanisms of Protection of Respiratory Tract

Toll-like receptors :

A

Recognize general features of a large number of pathogens

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7
Q

Innate and Adaptive Immune Mechanisms of Protection of Respiratory Tract

Interferons:

A

Induce antiviral state

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8
Q

Innate and Adaptive Immune Mechanisms of Protection of Respiratory Tract

IgA:

A

Secreted immunoglobulins in mucous

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9
Q

Seasonal Variation

March-May:
December-January:
November-May:

A

Rubella: spring peak (March-May)

Influenza: winter peak (December-January)

Rotavirus: winter peak (November-May)

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10
Q

Influenza Virus
Family:
Subfamilies:

A

Family: orthomyxoviridae

Subfamilies: Influenza A, B and C

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11
Q

Influenza Virus
Physical Characteristics:

enveloped?
genome:
segmented?

A

o Enveloped
o –ssRNA genome (segmented)
• A and B have 8 segments
• C has 7 segments

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12
Q

Influenza Virus

- Medical Significance:

A

o Frequent cause of severe respiratory disease
o Epidemics occur in the winter
o New strains can lead to world-wide epidemics (pandemics)

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13
Q

11 proteins encoded by 8 RNA segments:

A
  • HA (hemagglutinin)
  • NA (neuraminidase)
  • M1 (matrix)
  • M2 (ion channel)
  • PB1 (RNA-dependent RNA polymerase component)
  • PB1-F2 (may modulate viral replication and host responses, not found in all strains)
  • PB2 (RNA-dependent RNA polymerase component)
  • PA (RNA-dependent RNA polymerase component)
  • NP (associated with RNA-dependent RNA polymerase)
  • NS1 (blocks IFN-induced RNaseL pathway
  • NS2 (viral ribonucleoprotein transport- RNA from nucleus to cytoplasm
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14
Q

Influenza A Replication

Attachment:

A

Attachment: HA binds to sialic acid moieties on cell surface glycoproteins and glycolipids

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15
Q

Influenza A Replication

Penetration/Entry:

A
  • Virion internalized (receptor mediated endocytosis)
  • Reduced pH in endosome triggers a conformational change in HA, which induces fusion between the virion envelope and endosomal membrane
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16
Q

Influenza A Replication

Uncoating:

A

Uncoating: M2 ion channel allows protons to enter into virion interior, freeing ribonucleoprotein complex (RNP); RNPs then transported to the nucleus (transcription takes place here- unusual for RNA virus)

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17
Q

Influenza A Replication

Ribonucleoprotein Transcription:

A
  • mRNA for viral protens

- cRNA (+sense copy of vRNA) to be used as a template to produce more vRNA (genomes)

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18
Q

Influenza A Replication
Assembly and Release

RNP assembly where?
RNPs interact with:
How do they acquire envelopes?
NA removes ____ from cell surface

A
  • RNP assembly in nucleus → transport to cytoplasm
  • RNPs interact with M1 (matrix) and acquire envelopes by budding through plasma membrane
  • NA removes sialic acid from cell surface to facilitate release
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19
Q

Influenza Virus

Hemagglutinin (HA):

A

Key to both infection and immunity

  • Functions in viral replication (attachment and penetration)
  • Major target of neutralizing Abs (NA is secondary target)
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20
Q

Influenza Virus
Synthesis and Cleavage

Made as a:
Activated by:
HA1 binds to:
HA2 contains:

A
  • Made as a single polypeptide (HA0)
  • Activated by proteolytic cleavage → HA1 and HA2 (which remain bound to each other)
    • HA1 binds receptors (sialic acid)
    • HA2 contains transmembrane domain and fusion peptide (FP located at N-terminus of HA2)
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21
Q

Influenza Virus
HA Fusion Mechanism

Neutral pH (~7.4):

A

Neutral pH (~7.4):

  • HA1+HA2 extends from virion envelope
  • HA1 binds to cell surface receptors
  • Fusion peptide not exposed to aqueous environment due to trimer configuration
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22
Q

Influenza Virus
HA Fusion Mechanism

Acidic pH (~5.3):

A

Acidic pH (~5.3):

  • Low pH induces conformational shift in HA
  • Fusion peptide is exposed, and inserts into target membrane
  • Membranes are drawn close together, are locally disrupted, and fuse
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23
Q

Influenza Virus
Neuraminidase (NA)

Removes sialic acid from cell surface:

A

Removes sialic acid from cell surface
- Facilitates release of virus from the cell surface (without it, newly budded virions could bind back to the infected cell from which they were just released)

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24
Q

Influenza Virus
Neuraminidase (NA)

Removes sialic acid from mucins:

A

Removes sialic acid from mucins

  • Destroy decoy receptors (normally inactivate virus)
  • Lowers viscosity of mucous (helps virus to spread)
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25
Q

Influenza Virus

Target of Antiviral Drugs:

A
  • Oseltamivir (Tamiflu): oral
    • Note: cannot be used against seasonal influenza A (H1N1) as most strains are resistant
  • Zamanivir (Relenza): inhalation
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26
Q

Other Antivirals Against Influenza:

A
  • Amantidine and Rimantidine:
    o MOA: target M2 ion channel to block uncoating
    o Issue: widely overused and misused; many (if not all) influenza strains have become resistant
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27
Q

Influenza Immunity and Vaccine Composition

Immunity:
Key Antigens:

A

Immunity: provided mainly by virus neutralizing Abs (Abs to HA better neutralizers than those against NA)

Key Antigens:
• HA: 9 subtypes
• NA: 15 subtypes

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28
Q

Major Influenzas Infecting Humans:

A
  • H1N1 (1977 and 2009 strains)
  • H2N2
  • H3N2
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29
Q

Influenza

Vaccine:

A

Vaccine: against 2 influenza A strains and 1 influenza B

2010-2011 Vaccine:
• A/California/7/2009 (H1N1)
• A/Perth/16/2009 (H3N2)
• B/Brisbane/60/2008

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30
Q

Influenza Pandemics:

A
  • 1918: H1N1 Spanish flu
  • 1957: H2N2 Asian flu
  • 1968: H3N2 Hong Kong flu (still in circulation today)
  • 1977: H1N1 Russian flu (still in circulation today)
  • 2009: H1N1 swine flu
    o Formed from the combination of 3 different preexisting strains
    • Eurasian swine (H1N1/H3N2)
    • Swine (H1/N2)
    • Triple Reassortment Swine (formed from segments of 3 previously known viruses)
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31
Q

Influenza
Antigenic Variation

Antigenic Drift:
Driven by:
Results in:

Antigenic Shift:
Occurs via:
Results in:

A

Antigenic Drift: minor antigenic changes in HA and NA, resulting from mutations
o Driven by selection for resistance to Abs
o Results in a need to change vaccine composition annually

Antigenic Shift: major change in HA or NA, sometimes both
o Occurs via genetic reassortment after infection of a cell with 2 different Influenza A viruses
o Results in a virus for which there is little pre-existing immunity in the human population (results in a pandemic)

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32
Q

1918 H1N1 Virus Pathogenicity:

A
  • Excellent genetic synergy (individual genome segments worked well together)
  • High replication potential in bronchial epithelium (high Pathogenicity potential)
  • Broad cell tropism (not trypsin dependent)
    o Most influenza virus trains require trypsin-like enzyme to cleave HA to HA1 and HA2
    o This virus could be cleaved by enzymes found in most cell types
  • Dysregulation of immune responses (cytokine storms)
  • Inhibition of IFN responses via NS1 protein
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33
Q

Avian Influenza H5N1
Basics:

Transmission to humans:
What limits its ability to replicate in humans?
How does it have a high pandemic potential?

A

Basics: highly pathogenic H5N1 virus circulating in avian populations in many parts of the world

Not easily transmitted to humans, but could adapt to be

Mutation of viral genes that currently limit its ability to replicate in humans

Reassortment with viruses that replicate well in humans
- Have a high pandemic potential

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34
Q

Avian Influenza H5N1

Determinants of Pathogenicity:
Only transmissible to humans on exposure to:
Hemagglutinin H5 contains:
Preference for avian influenza receptors:
What allows HA cleavage by enzymes present in many cell types?

A

Only transmissible to humans on exposure to high doses
• Little to no ability to transmit from person to person

Hemagglutinin H5 contains 2 key pathogenicity determinants:

Preference for avian influenza receptors (sialic acid with alpha 2,3-linkage)

  • Humans have sialic acid with alpha 2,6-linkage
  • May also have avian-like receptors deeper in the human respiratory tract (not easy for the virus to access)

Multibasic amino acid sequence at HA cleavage site allows HA cleavage by enzymes present in many cell types

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35
Q

Paramyxoviridae
Family:
Subfamilies:

A

Family: Paramyxoviridae

Subfamily: Paramyxovirinae, Pneumovirinae

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36
Q

Paramyxoviridae
Paramyxovirinae

Genus: Paramyxovirus:

A

Genus: Paramyxovirus:
➢ Human Parainflueznavirus 1 (HPIV-1)
➢ Human Parainfluenzavirus 2 (HPIV-3)

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37
Q

Paramyxoviridae
Paramyxovirinae

Genus: Rubulavirus:

A

Genus: Rubulavirus
➢ Mumps Virus
➢ HPIV-2
➢ HPIV-4

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38
Q

Paramyxoviridae
Paramyxovirinae

Genus: Morbilivirus:

A

• Genus: Morbilivirus

➢ Measles Virus

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39
Q

Paramyxoviridae
Pneumovirinae

Genus: Pneumovirus:

A

Genus: Pneumovirus

➢ Respiratory Syncytial Virus (RSV)

40
Q

Paramyxoviridae
Physical Characteristics:
Genome:

A

Enveloped
RNA genome:
• -ssRNA (only one segment)

41
Q

Paramyxoviridae
Enveloped

How many glycoproteins?
Exceptions:

A

Most have 2 glycoproteins:

  • HN (has both HA and NA activities)
  • F (fusion activity; activated by proteolytic cleavage of F0 → F1 and F2)

Exceptions:

  • Measles (has H, with HA activity only, and F)
  • RSV (has G, which binds receptor but has no HA and NA activity, and F)
42
Q

Laryngitis/Croup

Cause:

A

Human Parainfluenza Viruses

43
Q

Croup

Seen in what pop.?
Infection and inflammation of:

A

Croup: seen in infants and young children

Infection and inflammation of larynx and upper airway (may also involve trachea and bronchi)

44
Q

Croup

Narrows airway, resulting in:
Other symptoms include:

A 
Narrows airway, resulting in:
•	“Barking” cough
•	Stridor (characteristic sound on inhalation) 
•	Hoarseness
•	Respiratory distress

Other symptoms include:
• Fever
• N/V

45
Q

Laryngitis

Seen in what pop.?
Life threatening?
Can also be caused by:

A

Laryngitis: seen in adults and older children

Respiratory tract is wider and therefore it is not life-threatening (swelling does not restrict airway as much)

Can also be caused by other infectious agents and conditions

46
Q

Tracheobronchitis

Lower Respiratory Tract Infection:
Major Symptoms:

A

Lower Respiratory Tract Infection: infection of the trachea and bronchi

Major Symptoms: coughing and wheezing

47
Q

Tracheobronchitis
Most cases due to viral causes

Adults: (2)
Children: (2)

A
  • Adults: influenzavirus, adenovirus

- Children: parainfluenzavirus, influenzavirus

48
Q

Tracheobronchitis

Nonviral causes:

A
  • Pertussis

- Other bacterial infections

49
Q

Bronchiolitis

Infection/inflammation of the bronchioles:
Adults:
Children:

A

Infection/inflammation of the bronchioles: small airways between bronchi and alveoli
o Adults: rarely seen
o Children: life-threatening (especially in those under one year of age)

50
Q

Bronchiolitis

Symptoms:
Cause:

A

Symptoms: dyspnea and cough

Cause: Respiratory Syncytial Virus (RSV

51
Q

Pharyngitis

A

Sore throat: usually also accompanied by other symptoms

52
Q

Pharyngitis
Sore throat

Infants:

A

Infants:
• Adenovirus (involvement of tonsils and adenoids)
• HSV 1

53
Q

Pharyngitis
Sore throat

Children:

A

Children:
• Adenovirus
• Coxsackievirus (herpangina)

54
Q

Pharyngitis
Sore throat

Adults:

A

Adults:
• Adenovirus
• Coxsackievirus

55
Q

Human Metapneumonvirus

A
  • Discovvered in the the Netherlands in 2001, found worldwide
  • Close relative of RSV
  • Second-most common cause of LRT infections in young children, after RSV
  • High rate of seropositivity (~100%) in older children
  • Elderly, the immunocompromised, and persons with chronic obstructive pulmaonry disease are also at risk of severe human metapneumovirus infection
56
Q

Pneumonia

Infection/inflammation of:
Common illness in all age groups:

A

Infection/inflammation of the lungs

Common illness in all age groups: chest pain, cough, fever, difficulty breathing, fatigue
o Common cause of death in the elderly

57
Q

Pneumonia
Common viral causes

Young Children:

A

Young Children:
• RSV
• Influenzavirus

58
Q

Pneumonia
Common viral causes

Older Children:

A

Older Children:
• Influenzavirus
• Parainfluenzavirus
• (Adenovirus)

59
Q

Pneumonia
Common viral causes

Adults:

A

Adults:
• Influenzavirus
• Adenovirus

60
Q

Paramyxovirus Zoonoses
Henipaviruses

Hendra Virus:

A
  • Natural host fruit bats
  • Hendra Virus
  • Discovered in 1994 in Australia
  • Human case fatality rate ~ 60%
61
Q

Paramyxovirus Zoonoses
Henipaviruses

Nipah virus

A

IDed in 1999 in pigs in Malasia
>200 humancases with >100 deaths
Numerous additional outbreaks in SE Asia, New Guinea, Australia
Human fatality rate ~50%

62
Q

Mumps

Basics:

A 
Basics: common childhood disease
o	Humans only natural reservoir
o	Transmission by salivary or respiratory secretions 
o	14-24 day IP
o	Less infectious than measles
63
Q

Mumps

Frequent Manifestations: (5)

A
  • Painful swelling of parotid gland
  • Swelling of cheeks and jaws
  • Ear pain
  • Fever
  • Headaches
64
Q

Mumps

Less Common Manifestations: (3)

A
  • Viral meningitis
  • Inflammation of testes (orchitis; more likely in older individuals and can cause sterility)
  • Rash
65
Q

Mumps
Prevention:
Dosing:

A

MMR vaccine

Dosing:
• 1st dose at 12-18 months (as early as 6 months in an epidemic)
• 2nd dose at 4-6 years

66
Q

Measles, Mumps and Rubella trivalent vaccine

Measles:
Mumps:
Rubella:

A

o Measles, Mumps and Rubella trivalent vaccine
• Measles: Attenuvax (Enders’ attenuated Edmonton strain)
• Mumps: Mumpsvax (Jeryl Lynn B level strain)
• Rubella: Meruvax II (Wistar RA 27/3 strain of live attenuated rubella virus)

67
Q

Measles (Rubeola)
Basics:
Best known for causing:
infectious?

A

Basics:
o Best known for causing a skin rash, although it is a respiratory pathogen
o Highly infectious
o Still an important disease in many parts of the world (prevented by MMR vaccine in US)
• Although 156 cases in 2011 is the highest number seen since 1996
• Most of these were in people who were unvaccinated and traveling abroad

68
Q

Measles (Rubeola)

Death Rate:
Transmission:
IP:

A
  • Death Rate: low in developed countries, but can be significant in people who are malnourished
  • Transmission: respiratory spread
  • IP: 14-18 days
69
Q

Measles (Rubeola)

Manifestations: (6)

A

o High fever
o Malaise
o Cough and coryza (symptoms of head cold)
o Headache
o Conjunctivitis
o Rash (5-7 days; begins on face and spreads to trunk and limbs)

70
Q

Measles (Rubeola)

Complications:
Prevention:

A 
Complications:
o	Diarrhea
o	Pneumonia
o	Encephalitis
o	Corneal ulceration

Prevention: MMR vaccine

71
Q

Rubella

Family:
Genome:
IP:

A
  • Family: Togaviridae
  • Genome: +ssRNA genome (one segment)
  • IP: 12-23 days
72
Q

Rubella

Symptoms: (4)

A

o LN swelling
o Maculopapular rash
o Fever
o Risk of congenital infection in pregnant women is greatest concern

73
Q

Rubella

Birth defects include:

A 
➢	Deafness
➢	Mental retardation
➢	Motor control deficits
➢	Heart, brain or eye malformations
➢	Enlarged liver and/or spleen
➢	Encephalitis
➢	Meningitis
74
Q

The “Common Cold”:

A

Viral infection of nose and throat

75
Q

The “Common Cold”
Symptoms:
Duration: 1-2 weeks

A 
-	Symptoms:
o	Sneezing/runny nose/nasal congestion
o	Watery eyes and drooping eyelids
o	Cough
o	Pharyngitis 
o	Mild/no fever

Duration: 1-2 weeks

76
Q

Coronavirus characteristics

Enveloped:
Nucleocapsid:
Genome:

A
  • Enveloped virion
  • Nucleocapsid has helical symmetry
  • RNA genome, single-stranded, positive sense, single segment
  • Genome is 30 kb, very large for an RNA virus
77
Q

Coronavirus

Viral glycoproteins:

A
  • Spike (S) glycoprotein - responsible for attachment and entry
  • Envelope (E) glycoprotein - multiple functions, including roles in assembly and egress and modulating the host cell stress response
78
Q

Emerging Coronaviruses

A

SARS and MERS

79
Q

The “Common Cold”

Most common viral causes: (4)

A

o Rhinoviruses (picornaviridae)
o Coxackieviruses (picornaviridae)
o Coronaviruses
o Adenovirus

80
Q

Rhinoviruses (picornaviridae):

Pleconaril:

A

Rhinoviruses (picornaviridae): cause at least 50%; over 100 serotypes

Pleconaril: anti-rhinoviral drug that prevents uncoating of capsule

81
Q

Coxackieviruses (picornaviridae)

A

o Coxackieviruses (picornaviridae): most common in infants and kids (herpangina and hand, foot and mouth disease)

82
Q

Coxackieviruses (picornaviridae)

Symptoms:

A

• Symptoms: fever, sore throat, headache, anorexia, vomiting, convulsions

83
Q

Coxackieviruses (picornaviridae)

Lesions:

A

• Lesions: develop after 2 days of symptoms; small papulovesicular lesions on the tonsils, soft palate and tongue
➢ Heal in 1-5 days
➢ Can also occur on hands, feet and in diaper area (Hand, Foot and Mouth Disease)
•

84
Q

Coxackieviruses (picornaviridae)

Resolution:

A

Resolution: more rapid than HSV (can look similar)

85
Q

Coronaviruses:
Adenovirus:

A

Coronaviruses: SARS
Adenovirus: over 50 serotypes

86
Q

Picornavirus and Infections of the Skin and Mucous Membranes

Picornavirus size:
Enveloped?
Genome:

What cause infections of the skin/mucous membranes?

A
  • Picornavirus are very small, nonenveloped viruses with single-stranded, plus-sense RNA genomes
  • Certain Picornaviruses, esp. certain Coxsackieviruses, as well as Echoviruses and Enterovirus 71, cause infections of the skin/mucous membranes
87
Q

Picornavirus Virus

Spread by:

A
  • Spread by saliva, mucous, or feces

- Coxsackievirus infections tend to occur in epidemics

88
Q

Hand, Foot, and Mouth Disease

A

Associated with Coxsackie A Virus, esp. type A16, Enterovirus 71

  • Recently, an outbreak of severe HFMD was caused by Coxsackie A Virus A6 in Alabama
  • Outbreaks in the US tend to be small, some larger outbreaks in Asian countries with thousands affected
89
Q

Herpangina (mouth blisters and ulcers)

A

Associated with certain types of Coxsackie A Virus, Coxsackie B Virus, and Echoviruses

90
Q

Viruses causing Common Cold:

A

Rhinoviruses and other Picornaviruses, Coronaviruses,

Parainfluenzaviruses, Adenovirses

91
Q

Viruses causing Pharyngitis:

A

Parainfluenzaviruses, Rhinoviruses and other
Picornaviruses, Influenza A and B Virus, Cytomegalovirus, Epstein-
Barr Virus, Herpes Simplex Virus, Adenoviruses

92
Q

Viruses causing Bronchitis:

A

Parainfluenzaviruses, Respiratory Syncytial Virus,

Influenza A and B Viruses, Metapneumovirus

93
Q

Viruses causing Bronchiolitis:

A

Parainfluenzaviruses, Respiratory Syncytial Virus,

Metapneumovirus

94
Q

Viruses causing Croup:

A

Parainfluenzaviruses, Respiratory Syncytial Virus,

Metapneumovirus

95
Q

Viruses causingInfluenza:

A

Influenza A and B Viruses

96
Q

Viruses causing Bronchopneumonia:

A

Influenza A and B Viruses, Respiratory Syncytial

Virus, Parainfluenzaviruses

97
Q

Viruses causing Pneumonia:

A

Pneumonia - Influenza A and B Viruses, Adenoviruses, Novel

Coronaviruses (SARS-CoV, MERS-CoV), Parainfluenzaviruses

Micro Exam 3 (11 decks)

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