35.1 Examples of Viral Disease Flashcards
(160 cards)
1
Q
Influenza
A
flu virus
2
Q
Influenza structure
A
- Enveloped
- Spikes (HA and NA)
- Helical nucleoprotein
- (-)ssRNA in 8 segments and 11 genes
3
Q
Influenza epidemics
A
Mutations in haemagglutinin, neuraminidase; antigenic drift = seasonal epidemics
4
Q
Influenza spread
A
Respiratory droplets
5
Q
Influenza infects and why
A
Respiratory epithelial cells in the nasopharyngeal and oropharyngeal spaces - lots of sialic acid on cell surface
6
Q
Main human influenza classes
A
A, B, C, D
7
Q
Severe strains of influenza
A
H1N1, H3N2
8
Q
Influenza Baltimore class
A
V (-ssRNA)
9
Q
Influenza genetic makeup
A
Linear (-)ssRNA within viral ribonuclearproteins
10
Q
Haemagglutinin
A
Influenza surface protein used to interact with alpha-2,6-sialic acid linkages and induce receptor-mediated endocytosis
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
12
Q
Influenza genome replication
A
Viral RNA-dependent RNA polymerases produce +ssRNA for formation of proteins, or as a template for more -ssRNA
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
14
Q
Influenza nucleoproteins
A
PA, PB1, PB2 (RNA-dependent RNA polymerase)
15
Q
Neuraminidase
A
Cleave haemagglutinin-sialic acid linkages to allow escape of nascent virions
16
Q
Baloxavir marboxil
A
Inhibitor of cap snatching to treat influenza infection
17
Q
Favipiravir
A
Inhibitor of influenza RNA-dependent RNA polymerase
18
Q
Oseltamivir, zanamivir, relenza
A
Neuraminidase inhibitor to treat influenza infection
19
Q
Amantadine
A
M2 channel blocker
20
Q
Influenza vaccine
A
Killed/live attenuated vaccine of 4 major A/B strains
21
Q
SARS-CoV-2 infects
A
Mucosal epithelial cells
22
Q
SARS spread
A
Aerosol droplets
23
Q
Coronaviruses: structure, examples
A
Structure:
- Lipid envelope
- Helical capsid
- S1 and S2 spike proteins
- (+)ssRNA
E.g.s: Common cold, SARS, MERS
24
Q
SARS-CoV-2 Baltimore class
A
IV (+ssRNA)
25
Coronavirus protenome/genome
27 proteins from 13 genes
26
Site of infection of coronavirus
Nasopharyngeal epithelium/type II alveolar cells
27
Mechanism of entry of coronavirus
TMPRSS2 (serine protease) used to cleave S1 domain of spike protein, exposing S2 fusion domain for binding with ACE2 and endocytosis
28
Endosome escape of coronavirus
pH decrease or cathepsin (protease) action alters binding affinity and enables membrane fusion
29
Coronavirus genome replication
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
30
Cap snatching
Viral cleavage of host mRNA and incorporation of the 5' 7-methyguanoside cap to enable translation
31
Roles of papain-like protease (PLpro)
Break down ISG15 to oppose type I interferon response and promote inflammation, leading to severe COVID-19
32
Immune evasion by SARS-CoV-2
PLpro to decrease interferons (IFNs)
Down-regulation of MCH-I on infected cells
33
COVID-19 pathophysiology
Severe pulmonary and cardiac inflammation and cytotoxicity, leading to surfactant disorders and myocardial scarring
34
Treatment of COVID-19
Fluids to prevent sepsis, oxygen support, pharmacology like dexamethasone
35
Pharmacological agents to treat SARS-CoV-2 infection
Remdesivir and dexamethasone
36
Dexamethasone MoA
Long-acting corticosteroid, decreases inflammation by down-regulating polymorphonuclear leukocytes and reversing increased capillary permeability
37
Remdesivir
Coronavirus RNA-dependent RNA polymerase inhibitor
38
SARS-CoV-2 vaccines
mRNA
Adenovirus vectored (ChAdOx1)
39
Polio infects
Grey matter in anterior horn of spinal cord and brain
40
Polio structure
- Icosahedral nucleocapsid shell
- (+)ssRNA
- No envelope until acquired from host
41
Poliomyelitis Baltimore class
IV (+ssRNA)
42
Polio infection symptoms
Mild (abortive), gastrointestinal (nausea, vomiting, pain), meningeal (can progress to motor neuron death and paralysis)
43
Prevalence of paralytic poliomyelitis
0.3% of cases
44
Major poliovirus proteins
RNA-dependent RNA-polymerase, proteases, VP surface proteins
45
Entry of poliovirus to host cells
Engage CD155 receptors on host epithelium and motor neurons for endocytosis
46
Replication of poliovirus genome
- 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
47
Polio spread
Faecal-oral route
48
IRES
Internal ribosome entry site - 5' region of poliovirus +ssRNA used to attach ribosomes and initiate translation
49
Enveloped viruses
Influenza, SARS-CoV-2, HIV, EBV, HBV
50
Non-enveloped viruses
Poliovirus, HPV
51
Polio pathogenesis
- Lysis of gut epithelial cells
- Paralysis of motor neurons
52
Poliovirus immune evasion
Resistance to acidity (survive stomach), rapid replication and virion maturation, antigenic variation
53
Polio treatment
Supportive care; analgesics
54
Poliomyelitis vaccine
Salk - Inactivated injectable
Sabin - Oral live attenuated
55
Risks of live attenuated polio vaccine
Risk of reversion in 3 per million, leading to vaccine-derived poliomyelitis (vdPM)
56
HIV infects
CD4+ T helper cells
57
HIV structure
- Nucleoprotein core (RT and RNA)
- Icosahedral with conical capsid
- Envelope
- Attachment proteins
- lentivirus
58
HIV envelope derived from what membrane
Plasma membrane of previously infected cell
59
HIV Baltimore class
VI (+ssRNA-RT)
60
HIV genome
2 single strands of identical RNA
3 open reading frame and 9 genes coding 16 proteins
61
HIV peptides (3)
- gag: capsid protein
- pol: reverse transcriptase
- env: envelope proteins (gp120 & gp41)
62
HIV structural proteins
Envelope - gp41, gp120. Capsid/matrix - p24, p17
63
Vif (viral infectivity factor)
APOBEC3G inhibitor; normally functions to interfere with viral replication in retroviruses
64
vpr (viral protein R)
Interferon (IFN) downregulator
65
Nef (negative regulatory factor)
MHC-I expression downregulator
66
Entry of HIV
gp120 binds CD4, then CCR5, allowing insertion of gp41 and endocytosis
67
Escape of HIV from endosome
Neutral pH endosome; gp41 distal tips inserted to lipid bilayer to reduce integrity and pull apart
68
HIV genome replication
- Reverse transcriptase produces ssDNA copy
- DNA-dependent DNA-polymerase of virus forms dsDNA
- Integrase inserts this to host genome for standard eukaryotic transcription
69
Transcription factor driving vDNA upregulation
NF-kB, following inflammatory activation of CD4 T-cell
70
Emergence of nascent HIV virions
Cell-free (within ECM), cell-to-cell (virological synapses)
71
How does antigenic variation of HIV occur? Consequences?
- Low-fidelity replication of proteins means that significant differences in antigen structure (env) occurs
- Evasion of adaptive immunity
72
Mechanism of HIV clearance
Chronic non-progressors produce produce broadly-acting antibodies to limit spread of virions and keep T-cell levels high
73
T-cell threshold for AIDS
<200 cells/ml
74
Issues with AIDS
- T-cell depletion impairs adaptive response activation
- Leads to inflammatory responses and MALT damage which can worsen T-cell depletion
75
HIV vaccine
None
76
HIV vaccine approaches
CTL - use cytoplasmic antigen to stimulate CTLs and reduce infection levels before depletion
Immunoglobulin - Produce antibodies against env
77
HIV symptoms
Flu-like illness initially
Viral load drop = asymptomatic until AIDS
78
Treatment of HIV
Antiretroviral therapy (ART)
Reverse transcriptase inhibitor
79
Zidovudine (AZT)
RT chain inhibitors
80
Nevirapine
Direct RT inhibitor
81
Saquinavir
HIV protease inhibitor
82
Raltegravir
HIV integrase inhibitor
83
Maraviroc
HIV; CCR5 antagonist (prevents HIV entry)
84
Hepatitis
Inflammation of the liver, usually caused by a viral infection
HBV= DNA virus
HCV= RNA virus
85
Difference between HBV and HCV
HBV = DNA virus
- Reverse transcriptase
- Can integrate genome
- Risk of hepatocellular cancer
HCV = RNA virus
86
Structure of Hepatitis B
- Enveloped
- dsDNA-RT
87
Hepatitis symptoms
Malaise, stool darkening, jaundice, paler urine
88
Long-term issues with hepatitis
Hypoalbuminaemia, clotting deficiency (decreased vitamin K reduction), metabolic disturbance
89
HAV Baltimore class
IV (+ssRNA)
90
HAV spread
Faecal-oral route
91
HBV Baltimore class
VII (dsDNA-RT)
92
Diagnostic marker for Hepatitis
Elevated ALT
93
Surface antigens of HBV
S/M/L HBsAg
94
Entry of HBV
L-HBsAg engages NTCPRs on hepatocytes for internalisation
95
HBV genome replication
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
Issues with cccDNA
Highly stable, can be latent and can modulate DNA for neoplasia (HCC). Replicated with host cells
97
Treatment of HBV
RT inhibitors, IFN-a to stop spread
98
Tenofovir
HBV rt inhibitor
99
HBV nucleocapsid
Icosahedral
100
How long may HBV stay infectious on a surface for?
1 month
101
HBV spread
Bodily fluid transmission; chronic carrier status
102
HBV Vaccine
Recombinant subunit, delivering L-HBsAg
103
HCV Baltimore class
IV (+ssRNA-RT)
104
Hepatocellular carcinoma
Cirrhotic liver (associated with hepatitis B and with alcoholism)
105
HCV structure
Icosahedral, enveloped
106
HCV replication
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
HCV treatment
interferon and ribavirin
108
HCV vaccine
none
109
HBV/HCV pathogenesis
cell killing by cytotoxic T-cells
110
Mononucleosis
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
EBV infects
- Oropharynx
- Liver(hepatitis and hepatomegaly, elevated liver enzymes)
- B cells
112
EBV
Epstein-Barr virus (cause of mononucleosis and other disorders)
113
HHV4 (human herpesvirus 4) is also known as
EBV
114
EBV Baltimore class
I (dsDNA)
115
Prevalence of EBV infection
90% worldwide
116
Symptoms of EBV infection
Asymptomatic, can lead to mononucleosis (non-specific symptoms with lymph node swelling and extreme tiredness) or lymphomas
117
Entry of EBV to host cells (nasopharynx)
BMRF-2 with B1-integrins, gH with avB6-integrins, gL with avB8-integrins
118
Entry of EBV to host cells (B-lymphocytes)
gp350 with CD21, gp42 with MHC2
119
EBV genome replication
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
EBV structure
HHV4
- Enveloped
- dsDNA
- Tegument proteins around capsid
121
Latency of EBV - genomic changes
Forms circular, plasmid-like genome in nucleus
122
Cancers associated with EBV
Burkitt lymphoma, nasopharyngeal carcinoma
123
Nasopharyngeal carcinoma
Malignant tumour of nasopharyngeal epithelium associated with EBV
124
Burkitt's lymphoma
Malignant cancer of B lymphocytes associated with EBV infection
125
Symptoms of EBV
Asymptomatic until leading to:
- Glandular fever/mononucleosis
- Cancers
126
Treatment of EBV
NSAIDs - ease swelling without potent immunosuppression that further activates the virus
127
EBV vaccine
None
128
Acyclovir
Herpes prodrug
129
HPV infects
Keratinocytes
130
Papilloma virus (HPV)
Warts, cervical cancer
131
HPV Baltimore class
I (dsDNA)
132
HPV transmission
Skin to skin contact (sexually transmitted)
133
Tissue tropism of HPV
Keratinocytes; basal layer of epithelium
134
HPV treatment
No treatment. Just manage issues that HPV can cause.
135
HPV structure
- No envelope
- Icosahedral
- dsDNA
136
HPV vaccine
Recombinant
A vaccine that can prevent cervical cancer, pre-cancerous genital lesions (or sores), and genital warts caused by genital HPV infection
137
HPV replication
Genome integrated to host; unregulated expression of viral transforming protein E6 and E7
138
Herpesviridae Baltimore class
I dsDNA
139
Herpesviridae structure
- Large
- Enveloped
- dsDNA
- Icosahedral capsid
- Tegument proteins around capsid
140
What are the human herpes viruses?
1= herpes simplex 1
2= herpes simplex 2
3= varicella zoster virus
4= epstein barr virus
5= cytomegalovirus
141
Symptoms of HHV-1
Painful, itchy skin lesions on the lips which last 7 to 10 days
Initial infections can be accompanied by flulike signs and symptoms
142
Cells targeted by HHV-1
Mucoepithelial cells above the waist
143
Transmission of HHV-1
Close contact
144
Entry of HHV-1 to cell
Receptor mediated endocytosis
145
Release of HHV-1 new virions
Lysis
146
Treatments of HHV-1
Antivirals
147
HHV-1 latency - where?
Trigeminal ganglion neurons
148
Symptoms of HHV-2
Painful blisters on genitals and in genital region
Labial and genital herpes
149
Release of new HHV-2 virions
Budding - membrane exocytosis
150
Latency of HHV-2 - where?
Sacral ganglion neurons
151
Symptoms of HHV-3
- Chicken pox rash begins on trunk, extends to limbs and head
- Fever
- Shingles (after latency)
152
HHV-3 infects what cells
Upper respiratory tract, travels in blood to skin, where rash occurs
153
HHV3 latency - where?
Dorsal root ganglia
154
Herpes viruses infect neurons to become latent - how?
Retrograde axonal flow into ganglia cells
155
In latently infected cells, what is the DNA of VZV associated with?
Located in nucleus, but not integrated into cellular DNA
156
Treatment of HHV-3
Paracetamol for fever in chickenpox
Antivirals effective for shingles
157
Cytomegalovirus
HHV-5
158
Symptoms of HH5-V
Asymptomatic/mononucleosis-like:
- Fever
- Sore throat
159
Symptoms of child whose mother became infected with HHV-5 during pregnancy
Long term intellectual disability and hearing loss
160
HHV-5 treatment
Antivirals
