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Sophie - Principles of Pathology - Year 2 > 35.1 Examples of Viral Disease > Flashcards

35.1 Examples of Viral Disease Flashcards

1
Q

Influenza

A

flu virus

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2
Q

Influenza structure

A
  • Enveloped
  • Spikes (HA and NA)
  • Helical nucleoprotein
  • (-)ssRNA in 8 segments and 11 genes
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3
Q

Influenza epidemics

A

Mutations in haemagglutinin, neuraminidase; antigenic drift = seasonal epidemics

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4
Q

Influenza spread

A

Respiratory droplets

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5
Q

Influenza infects and why

A

Respiratory epithelial cells in the nasopharyngeal and oropharyngeal spaces - lots of sialic acid on cell surface

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6
Q

Main human influenza classes

A

A, B, C, D

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7
Q

Severe strains of influenza

A

H1N1, H3N2

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8
Q

Influenza Baltimore class

A

V (-ssRNA)

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9
Q

Influenza genetic makeup

A

Linear (-)ssRNA within viral ribonuclearproteins

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10
Q

Haemagglutinin

A

Influenza surface protein used to interact with alpha-2,6-sialic acid linkages and induce receptor-mediated endocytosis

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11
Q

Escape of influenza vRNPs to cytosol

A

Protonation of endosome and intraviral space by M2 channels leads to injection of fusion protein between virus and endosome membrane, allowing vRNPS to exit to cytoplasm and move to nucleus for replication

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12
Q

Influenza genome replication

A

Viral RNA-dependent RNA polymerases produce +ssRNA for formation of proteins, or as a template for more -ssRNA

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13
Q

Effect of dsRNA intermediates formed during influenza replication

A

Act as signal for host cell to produce and secrete IFN-alpha/beta to prevent spread

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14
Q

Influenza nucleoproteins

A

PA, PB1, PB2 (RNA-dependent RNA polymerase)

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15
Q

Neuraminidase

A

Cleave haemagglutinin-sialic acid linkages to allow escape of nascent virions

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16
Q

Baloxavir marboxil

A

Inhibitor of cap snatching to treat influenza infection

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17
Q

Favipiravir

A

Inhibitor of influenza RNA-dependent RNA polymerase

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18
Q

Oseltamivir, zanamivir, relenza

A

Neuraminidase inhibitor to treat influenza infection

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19
Q

Amantadine

A

M2 channel blocker

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20
Q

Influenza vaccine

A

Killed/live attenuated vaccine of 4 major A/B strains

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21
Q

SARS-CoV-2 infects

A

Mucosal epithelial cells

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22
Q

SARS spread

A

Aerosol droplets

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23
Q

Coronaviruses: structure, examples

A

Structure:
- Lipid envelope
- Helical capsid
- S1 and S2 spike proteins
- (+)ssRNA

E.g.s: Common cold, SARS, MERS

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24
Q

SARS-CoV-2 Baltimore class

A

IV (+ssRNA)

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25
Q

Coronavirus protenome/genome

A

27 proteins from 13 genes

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26
Q

Site of infection of coronavirus

A

Nasopharyngeal epithelium/type II alveolar cells

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27
Q

Mechanism of entry of coronavirus

A

TMPRSS2 (serine protease) used to cleave S1 domain of spike protein, exposing S2 fusion domain for binding with ACE2 and endocytosis

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28
Q

Endosome escape of coronavirus

A

pH decrease or cathepsin (protease) action alters binding affinity and enables membrane fusion

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29
Q

Coronavirus genome replication

A

RNA-dependent RNA polymerases used for subgenomic transcription of +ssRNA in vesicle
-produces dsRNA
-and a precursor of -ssRNA that acts as a template for further +ssRNA development

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30
Q

Cap snatching

A

Viral cleavage of host mRNA and incorporation of the 5’ 7-methyguanoside cap to enable translation

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31
Q

Roles of papain-like protease (PLpro)

A

Break down ISG15 to oppose type I interferon response and promote inflammation, leading to severe COVID-19

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32
Q

Immune evasion by SARS-CoV-2

A

PLpro to decrease interferons (IFNs)

Down-regulation of MCH-I on infected cells

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33
Q

COVID-19 pathophysiology

A

Severe pulmonary and cardiac inflammation and cytotoxicity, leading to surfactant disorders and myocardial scarring

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34
Q

Treatment of COVID-19

A

Fluids to prevent sepsis, oxygen support, pharmacology like dexamethasone

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35
Q

Pharmacological agents to treat SARS-CoV-2 infection

A

Remdesivir and dexamethasone

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36
Q

Dexamethasone MoA

A

Long-acting corticosteroid, decreases inflammation by down-regulating polymorphonuclear leukocytes and reversing increased capillary permeability

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37
Q

Remdesivir

A

Coronavirus RNA-dependent RNA polymerase inhibitor

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38
Q

SARS-CoV-2 vaccines

A

mRNA

Adenovirus vectored (ChAdOx1)

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39
Q

Polio infects

A

Grey matter in anterior horn of spinal cord and brain

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40
Q

Polio structure

A
  • Icosahedral nucleocapsid shell
  • (+)ssRNA
  • No envelope until acquired from host
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41
Q

Poliomyelitis Baltimore class

A

IV (+ssRNA)

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42
Q

Polio infection symptoms

A

Mild (abortive), gastrointestinal (nausea, vomiting, pain), meningeal (can progress to motor neuron death and paralysis)

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43
Q

Prevalence of paralytic poliomyelitis

A

0.3% of cases

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44
Q

Major poliovirus proteins

A

RNA-dependent RNA-polymerase, proteases, VP surface proteins

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45
Q

Entry of poliovirus to host cells

A

Engage CD155 receptors on host epithelium and motor neurons for endocytosis

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46
Q

Replication of poliovirus genome

A
  • RNA-dependent RNA polymerases replicate to form dsRNA and amplify +ssRNA levels in vesicle
  • The single, genomic strand produced is then translated as mRNA and polypeptide cleaved by proteases to form functional units
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47
Q

Polio spread

A

Faecal-oral route

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48
Q

IRES

A

Internal ribosome entry site - 5’ region of poliovirus +ssRNA used to attach ribosomes and initiate translation

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49
Q

Enveloped viruses

A

Influenza, SARS-CoV-2, HIV, EBV, HBV

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50
Q

Non-enveloped viruses

A

Poliovirus, HPV

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51
Q

Polio pathogenesis

A
  • Lysis of gut epithelial cells
  • Paralysis of motor neurons
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52
Q

Poliovirus immune evasion

A

Resistance to acidity (survive stomach), rapid replication and virion maturation, antigenic variation

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53
Q

Polio treatment

A

Supportive care; analgesics

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54
Q

Poliomyelitis vaccine

A

Salk - Inactivated injectable
Sabin - Oral live attenuated

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55
Q

Risks of live attenuated polio vaccine

A

Risk of reversion in 3 per million, leading to vaccine-derived poliomyelitis (vdPM)

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56
Q

HIV infects

A

CD4+ T helper cells

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57
Q

HIV structure

A
  • Nucleoprotein core (RT and RNA)
  • Icosahedral with conical capsid
  • Envelope
  • Attachment proteins
  • lentivirus
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58
Q

HIV envelope derived from what membrane

A

Plasma membrane of previously infected cell

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59
Q

HIV Baltimore class

A

VI (+ssRNA-RT)

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60
Q

HIV genome

A

2 single strands of identical RNA

3 open reading frame and 9 genes coding 16 proteins

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61
Q

HIV peptides (3)

A
  • gag: capsid protein
  • pol: reverse transcriptase
  • env: envelope proteins (gp120 & gp41)
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62
Q

HIV structural proteins

A

Envelope - gp41, gp120. Capsid/matrix - p24, p17

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63
Q

Vif (viral infectivity factor)

A

APOBEC3G inhibitor; normally functions to interfere with viral replication in retroviruses

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64
Q

vpr (viral protein R)

A

Interferon (IFN) downregulator

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65
Q

Nef (negative regulatory factor)

A

MHC-I expression downregulator

66
Q

Entry of HIV

A

gp120 binds CD4, then CCR5, allowing insertion of gp41 and endocytosis

67
Q

Escape of HIV from endosome

A

Neutral pH endosome; gp41 distal tips inserted to lipid bilayer to reduce integrity and pull apart

68
Q

HIV genome replication

A
  • Reverse transcriptase produces ssDNA copy
  • DNA-dependent DNA-polymerase of virus forms dsDNA
  • Integrase inserts this to host genome for standard eukaryotic transcription
69
Q

Transcription factor driving vDNA upregulation

A

NF-kB, following inflammatory activation of CD4 T-cell

70
Q

Emergence of nascent HIV virions

A

Cell-free (within ECM), cell-to-cell (virological synapses)

71
Q

How does antigenic variation of HIV occur? Consequences?

A
  • Low-fidelity replication of proteins means that significant differences in antigen structure (env) occurs
  • Evasion of adaptive immunity
72
Q

Mechanism of HIV clearance

A

Chronic non-progressors produce produce broadly-acting antibodies to limit spread of virions and keep T-cell levels high

73
Q

T-cell threshold for AIDS

A

<200 cells/ml

74
Q

Issues with AIDS

A
  • T-cell depletion impairs adaptive response activation
  • Leads to inflammatory responses and MALT damage which can worsen T-cell depletion
75
Q

HIV vaccine

A

None

76
Q

HIV vaccine approaches

A

CTL - use cytoplasmic antigen to stimulate CTLs and reduce infection levels before depletion

Immunoglobulin - Produce antibodies against env

77
Q

HIV symptoms

A

Flu-like illness initially

Viral load drop = asymptomatic until AIDS

78
Q

Treatment of HIV

A

Antiretroviral therapy (ART)

Reverse transcriptase inhibitor

79
Q

Zidovudine (AZT)

A

RT chain inhibitors

80
Q

Nevirapine

A

Direct RT inhibitor

81
Q

Saquinavir

A

HIV protease inhibitor

82
Q

Raltegravir

A

HIV integrase inhibitor

83
Q

Maraviroc

A

HIV; CCR5 antagonist (prevents HIV entry)

84
Q

Hepatitis

A

Inflammation of the liver, usually caused by a viral infection

HBV= DNA virus
HCV= RNA virus

85
Q

Difference between HBV and HCV

A

HBV = DNA virus
- Reverse transcriptase
- Can integrate genome
- Risk of hepatocellular cancer

HCV = RNA virus

86
Q

Structure of Hepatitis B

A
  • Enveloped
  • dsDNA-RT
87
Q

Hepatitis symptoms

A

Malaise, stool darkening, jaundice, paler urine

88
Q

Long-term issues with hepatitis

A

Hypoalbuminaemia, clotting deficiency (decreased vitamin K reduction), metabolic disturbance

89
Q

HAV Baltimore class

A

IV (+ssRNA)

90
Q

HAV spread

A

Faecal-oral route

91
Q

HBV Baltimore class

A

VII (dsDNA-RT)

92
Q

Diagnostic marker for Hepatitis

A

Elevated ALT

93
Q

Surface antigens of HBV

A

S/M/L HBsAg

94
Q

Entry of HBV

A

L-HBsAg engages NTCPRs on hepatocytes for internalisation

95
Q

HBV genome replication

A

Endosomal escape with viral uncoating, releasing dsDNA. dsDNA converted to dsRNA, and then to cccDNA (covalently closed circular DNA) retained in host nucleus outside of chromosomes

96
Q

Issues with cccDNA

A

Highly stable, can be latent and can modulate DNA for neoplasia (HCC). Replicated with host cells

97
Q

Treatment of HBV

A

RT inhibitors, IFN-a to stop spread

98
Q

Tenofovir

A

HBV rt inhibitor

99
Q

HBV nucleocapsid

A

Icosahedral

100
Q

How long may HBV stay infectious on a surface for?

A

1 month

101
Q

HBV spread

A

Bodily fluid transmission; chronic carrier status

102
Q

HBV Vaccine

A

Recombinant subunit, delivering L-HBsAg

103
Q

HCV Baltimore class

A

IV (+ssRNA-RT)

104
Q

Hepatocellular carcinoma

A

Cirrhotic liver (associated with hepatitis B and with alcoholism)

105
Q

HCV structure

A

Icosahedral, enveloped

106
Q

HCV replication

A

virus enters cell, RNA genome is translated into polyprotein.
2 proteases processes the polyprotein.
genome replication follows where RNA - strand is made and copied into more + strands, replicating the genome.

107
Q

HCV treatment

A

interferon and ribavirin

108
Q

HCV vaccine

A

none

109
Q

HBV/HCV pathogenesis

A

cell killing by cytotoxic T-cells

110
Q

Mononucleosis

A

condition caused by the Epstein-Barr virus and characterized by an increase in mononuclear cells (monocytes and lymphocytes) in the blood along with enlarged lymph nodes (lymphadenopathy), fatigue, and sore throat (pharyngitis)

111
Q

EBV infects

A
  • Oropharynx
  • Liver(hepatitis and hepatomegaly, elevated liver enzymes)
  • B cells
112
Q

EBV

A

Epstein-Barr virus (cause of mononucleosis and other disorders)

113
Q

HHV4 (human herpesvirus 4) is also known as

A

EBV

114
Q

EBV Baltimore class

A

I (dsDNA)

115
Q

Prevalence of EBV infection

A

90% worldwide

116
Q

Symptoms of EBV infection

A

Asymptomatic, can lead to mononucleosis (non-specific symptoms with lymph node swelling and extreme tiredness) or lymphomas

117
Q

Entry of EBV to host cells (nasopharynx)

A

BMRF-2 with B1-integrins, gH with avB6-integrins, gL with avB8-integrins

118
Q

Entry of EBV to host cells (B-lymphocytes)

A

gp350 with CD21, gp42 with MHC2

119
Q

EBV genome replication

A

Nasopharyngeal epithelium:
- Linear DNA transcribed by host RNA polymerase II in nucleus
- Replicated by viral DNA polymerase

B cells:
- Once in nucleus, vDNA acts as episome
- Aka genetic material used as host genetic material

120
Q

EBV structure

A

HHV4
- Enveloped
- dsDNA
- Tegument proteins around capsid

121
Q

Latency of EBV - genomic changes

A

Forms circular, plasmid-like genome in nucleus

122
Q

Cancers associated with EBV

A

Burkitt lymphoma, nasopharyngeal carcinoma

123
Q

Nasopharyngeal carcinoma

A

Malignant tumour of nasopharyngeal epithelium associated with EBV

124
Q

Burkitt’s lymphoma

A

Malignant cancer of B lymphocytes associated with EBV infection

125
Q

Symptoms of EBV

A

Asymptomatic until leading to:
- Glandular fever/mononucleosis
- Cancers

126
Q

Treatment of EBV

A

NSAIDs - ease swelling without potent immunosuppression that further activates the virus

127
Q

EBV vaccine

A

None

128
Q

Acyclovir

A

Herpes prodrug

129
Q

HPV infects

A

Keratinocytes

130
Q

Papilloma virus (HPV)

A

Warts, cervical cancer

131
Q

HPV Baltimore class

A

I (dsDNA)

132
Q

HPV transmission

A

Skin to skin contact (sexually transmitted)

133
Q

Tissue tropism of HPV

A

Keratinocytes; basal layer of epithelium

134
Q

HPV treatment

A

No treatment. Just manage issues that HPV can cause.

135
Q

HPV structure

A
  • No envelope
  • Icosahedral
  • dsDNA
136
Q

HPV vaccine

A

Recombinant

A vaccine that can prevent cervical cancer, pre-cancerous genital lesions (or sores), and genital warts caused by genital HPV infection

137
Q

HPV replication

A

Genome integrated to host; unregulated expression of viral transforming protein E6 and E7

138
Q

Herpesviridae Baltimore class

A

I dsDNA

139
Q

Herpesviridae structure

A
  • Large
  • Enveloped
  • dsDNA
  • Icosahedral capsid
  • Tegument proteins around capsid
140
Q

What are the human herpes viruses?

A

1= herpes simplex 1
2= herpes simplex 2
3= varicella zoster virus
4= epstein barr virus
5= cytomegalovirus

141
Q

Symptoms of HHV-1

A

Painful, itchy skin lesions on the lips which last 7 to 10 days

Initial infections can be accompanied by flulike signs and symptoms

142
Q

Cells targeted by HHV-1

A

Mucoepithelial cells above the waist

143
Q

Transmission of HHV-1

A

Close contact

144
Q

Entry of HHV-1 to cell

A

Receptor mediated endocytosis

145
Q

Release of HHV-1 new virions

A

Lysis

146
Q

Treatments of HHV-1

A

Antivirals

147
Q

HHV-1 latency - where?

A

Trigeminal ganglion neurons

148
Q

Symptoms of HHV-2

A

Painful blisters on genitals and in genital region

Labial and genital herpes

149
Q

Release of new HHV-2 virions

A

Budding - membrane exocytosis

150
Q

Latency of HHV-2 - where?

A

Sacral ganglion neurons

151
Q

Symptoms of HHV-3

A
  • Chicken pox rash begins on trunk, extends to limbs and head
  • Fever
  • Shingles (after latency)
152
Q

HHV-3 infects what cells

A

Upper respiratory tract, travels in blood to skin, where rash occurs

153
Q

HHV3 latency - where?

A

Dorsal root ganglia

154
Q

Herpes viruses infect neurons to become latent - how?

A

Retrograde axonal flow into ganglia cells

155
Q

In latently infected cells, what is the DNA of VZV associated with?

A

Located in nucleus, but not integrated into cellular DNA

156
Q

Treatment of HHV-3

A

Paracetamol for fever in chickenpox

Antivirals effective for shingles

157
Q

Cytomegalovirus

A

HHV-5

158
Q

Symptoms of HH5-V

A

Asymptomatic/mononucleosis-like:
- Fever
- Sore throat

159
Q

Symptoms of child whose mother became infected with HHV-5 during pregnancy

A

Long term intellectual disability and hearing loss

160
Q

HHV-5 treatment

A

Antivirals

Sophie - Principles of Pathology - Year 2 (43 decks)

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