1
Q
Coronavirus genome type?
A
Single-stranded, positive-sense RNA (~30 kb), polyadenylated and infectious.
2
Q
What is unique about coronavirus RNA size?
A
Largest known viral RNA genome.
3
Q
Coronavirus genome encodes what first?
A
A large polyprotein that is cleaved into nonstructural proteins.
4
Q
Key nonstructural proteins encoded by coronaviruses?
A
RNA-dependent RNA polymerase, methyltransferases, helicase.
5
Q
What comes after the big polyprotein in the genome?
A
Structural proteins (interspersed with nonstructural proteins).
6
Q
What does HE protein stand for and where is it found?
A
Hemagglutinin-esterase; found in HCoVs OC43 and HKU1 and some animal betacoronaviruses.
7
Q
Possible function of HE protein?
A
Assists in attachment and/or release of viral particles.
8
Q
HE protein similarity suggests what?
A
Past recombination with influenza C virus hemagglutinin.
9
Q
What happened to HE function with human adaptation?
A
Loss of receptor-binding activity and esterase function (adaptation to human sialic acid receptor).
10
Q
What are coronavirus spike proteins responsible for?
A
Viral attachment and stimulation of neutralizing antibodies.
11
Q
How do spike proteins look on the virion?
A
Petal-shaped projections.
12
Q
List the major structural proteins of coronaviruses.
A
Spike (S), Envelope (E), Membrane (M), Nucleocapsid (N); plus HE in OC43/HKU1.
13
Q
What is the N protein associated with?
A
Complexed with viral RNA (forms nucleocapsid).
14
Q
What are additional ORFs in coronaviruses thought to do?
A
Likely involved in immune evasion.
15
Q
Coronavirus replication strategy resembles which virus group?
A
Nidoviruses.
16
Q
What is a “nested set of mRNAs”?
A
A set of subgenomic mRNAs sharing a common 3′ polyadenylation.
17
Q
Coronavirus mutation rate per site per cycle?
A
~2 × 10^-6 per site per replication cycle.
18
Q
Why is coronavirus mutation rate lower than many RNA viruses?
A
3′→5′ exonuclease proofreading activity.
19
Q
Can coronaviruses recombine genetically?
A
Yes, if two CoVs co-infect the same cell.
20
Q
Where do coronaviruses develop/replicate?
A
Exclusively in the cytoplasm.
21
Q
Where do coronaviruses bud?
A
Into cytoplasmic vesicles from pre-Golgi ER membranes.
22
Q
How are coronaviruses released from the cell?
A
Exocytic secretory pathway.
23
Q
Which protein is critical for coronavirus release?
A
E protein.
24
Q
Coronavirus particle diameter by thin-section EM?
A
~70–80 nm.
25
Coronavirus particle size range by negative staining?
~60–220 nm.
26
Coronavirus morphology term (shape variability)?
Pleomorphic.
27
Length of coronavirus surface projections?
~20 nm long, widely spaced, petal-shaped.
28
Receptor for HCoV-229E and most alphacoronaviruses?
Aminopeptidase N (APN).
29
Receptor for HCoV-NL63 and SARS-CoV?
ACE2 (angiotensin-converting enzyme 2).
30
Receptor for mouse hepatitis virus (related to OC43)?
Carcinoembryonic antigen family receptor.
31
Receptor for HCoV-OC43 and bovine CoV?
9-O-acetylated neuraminic acid.
32
Receptor for MERS-CoV?
DPP4 (dipeptidyl peptidase 4).
33
What do these CoV receptors have in common?
They are ectopeptidases highly expressed in respiratory and enteric tracts.
34
Which HCoVs grow only with difficulty in tissue culture?
OC43 and HKU1.
35
How was 229E discovered in culture?
Cytopathic effect in human embryonic kidney cells.
36
How was NL63 discovered in culture?
Cytopathic effect in LLC-MK2 cells.
37
Which cells readily support SARS-CoV and MERS-CoV growth?
Vero cells.
38
How can OC43 and HKU1 be cultivated after adaptation?
In primary ciliated human airway epithelial cells.
39
Best method for detecting coronaviruses in clinical specimens?
PCR (most sensitive and convenient).
40
CAR CoV infections are found where globally?
Worldwide.
41
In temperate climates, CAR CoV infections are more common when?
Winter and spring.
42
During peak viral activity, CAR CoVs may account for up to what % of URIs?
Up to 35%.
43
Estimated % of adult colds caused by CAR CoVs?
~15%.
44
In infants, which HCoVs are more common than 229E/HKU1?
NL63 and OC43.
45
Epidemic cycles for OC43 and 229E?
Every 2–3 years.
46
Incidence of NL63 and HKU1 is described as…
Variable by year and location (limited data).
47
Is reinfection common with CAR CoVs?
Yes, reinfection is common.
48
Why is reinfection common?
Rapid decline of antibody levels after infection.
49
CAR CoV infection occurs at what ages?
All ages, most common in children.
50
Symptomatic-to-total infection ratio range?
~50% to 90% depending on age/method/definition.
51
In experimental infection with HCoV-229E, what % developed colds?
72% of infected adult volunteers.
52
MERS-CoV was first identified when and where?
2012 in Jeddah, Saudi Arabia.
53
Initial MERS patient outcome?
Died from respiratory and renal failure.
54
MERS-CoV was isolated from what sample type initially?
Sputum.
55
MERS-CoV is a betacoronavirus related to which bat CoVs?
HKU4 and HKU5.
56
Total confirmed MERS cases from 2012 to Mar 10, 2019?
2,374 cases.
57
Where were most MERS cases reported?
Saudi Arabia.
58
MERS secondary infections occurred mainly in what settings?
Family and hospital settings.
59
How many confirmed MERS cases occurred in the US (mentioned)?
Two unrelated cases.
60
Early years of MERS spread were mainly what type?
Nosocomial (hospital-acquired) spread.
61
Hospital areas/procedures linked to MERS spread?
Emergency rooms and aerosol-generating procedures.
62
Is fomite transmission possible for MERS?
Yes, virus detected in environment near patients.
63
Currently, about what % of MERS cases are primary infections?
~50%.
64
Primary MERS infections are often linked to what animal?
Camels.
65
Camel-to-human transmission routes listed?
Direct contact with secretions; raw camel milk; environmental contamination.
66
How long can MERS survive on hard surfaces (minimum)?
At least 48 hours.
67
Household transmission of MERS outside hospitals is…
Limited.
68
South Korea MERS outbreak dates?
May–June 2015.
69
South Korea MERS outbreak size and deaths?
186 infections, 38 deaths.
70
Factors contributing to Korea outbreak?
Delayed diagnosis, doctor-shopping, super-spreading, familial caregiving, poor infection control.
71
Why can antibody testing underestimate MERS prevalence?
Subclinical/mild infections may not develop detectable or lasting antibodies.
72
What immune response may persist longer than antibodies (SARS/MERS survivors)?
T-cell responses.
73
Primary source of human MERS infections?
Camels.
74
Where have MERS-positive dromedary camels been found?
Arabian Peninsula, Africa, Central Asia, Pakistan.
75
MERS antibodies in camels date back to what year?
1983
76
Genetic similarity between camel and human MERS viruses?
~98–99%.
77
Likely original source of MERS-CoV?
Bats (MERS-related viruses in African bats).
78
SARS epidemic began when and where?
Mid-November 2002 in Guangdong, China.
79
When did SARS gain global attention?
March 2003.
80
SARS spread was notable especially in what setting?
Hospitals (HCWs, patients, visitors, family).
81
Main regions with SARS cases?
China, Hong Kong, Taiwan, Singapore, Toronto.
82
SARS case fatality range in affected regions?
~7% to 17%.
83
SARS mortality in >65 or with underlying conditions?
~50%.
84
SARS mortality in children and adults under 24?
None reported.
85
When did global SARS transmission cease?
July 2003.
86
Last known SARS case?
Mid-2004.
87
Primary SARS transmission modes?
Droplet and contact; possible role for fomites.
88
What explains SARS “super-spreading events”?
Likely small-particle airborne transmission.
89
When are airborne precautions essential for SARS?
During aerosol-generating procedures.
90
SARS origin pathway suggested?
Bat virus → palm civets/market animals → humans.
91
Primary replication site for CAR CoVs?
Nasopharyngeal epithelium: ciliated cells (OC43, NL63, HKU1) and nonciliated cells (229E).
92
What causes CAR CoV cold-like symptoms?
Cell degeneration + chemokines/interleukins release.
93
CAR CoV incubation period?
~2 days.
94
Peak symptoms and shedding after CAR CoV inoculation?
3–4 days.
95
MERS receptor and site relevance?
DPP4; high expression in kidneys may contribute to renal disease.
96
MERS incubation median and range?
Median 7 days; range 2–17 days.
97
MERS severity spectrum?
Subclinical disease to lethal pneumonia.
98
Groups at highest risk for severe/fatal MERS?
Elderly and those with diabetes, renal disease, immunosuppression.
99
Common MERS symptoms?
Fever, shortness of breath, cough, diarrhea.
100
MERS early imaging finding?
Ground-glass appearance in lung periphery.
101
MERS imaging finding linked to worse outcomes?
Pleural effusion.
102
MERS ICU mortality range reported?
58% to 78%.
103
Key lab abnormalities in MERS?
Leukopenia, lymphopenia, thrombocytopenia; ↑LDH, ↑ALT, ↑AST.
104
MERS proinflammatory mediators prolonged in severe disease?
Interferon-α, IL-6, CXCL1.
105
MERS antibody responses in survivors vs fatal cases?
Survivors develop more rapid/robust antibodies than fatal cases.
106
MERS in pregnancy is associated with what?
Fetal and/or maternal demise.
107
SARS incubation typical and range?
Typically 4–7 days; may range 10–14 days.
108
SARS initial symptoms?
Fever + systemic influenza-like symptoms.
109
When do cough and dyspnea usually develop in SARS?
A few days to a week later.
110
About what % of SARS patients develop diarrhea?
~25%.
111
Are upper respiratory symptoms common in SARS?
No, rhinorrhea/sore throat are rare.
112
SARS chest radiograph pattern?
Scattered peripheral airspace opacification, often in lower zones.
113
SARS CT pattern?
Ground-glass opacification and consolidation, often subpleural.
114
Common hematologic finding in SARS?
Lymphopenia.
115
Which WBC pattern is linked to worse SARS outcomes?
Neutrophilia.
116
Other abnormal labs in SARS?
CK, LDH, AST (often abnormal).
117
About what % of SARS patients develop ARDS?
~25%.
118
SARS overall mortality rate reported?
~9% to 12%.
119
SARS risk factors for severe pulmonary disease/ARDS?
Age >50 and underlying conditions (diabetes, cardiac disease, chronic hepatitis).
120
Why is SARS deterioration in week 2 sometimes “immune-mediated”?
Clinical deterioration as virus levels decrease in week 2.
121
Best approach to diagnose CoV respiratory infections (CAR CoVs)?
RT-PCR (molecular methods).
122
Generic CoV PCR vs specific assays: sensitivity?
Generic test has lower sensitivity than specific systems.
123
MERS RT-PCR detection limit (approx.)
As few as 10–15 copies of viral RNA.
124
When were peak MERS virus titers detected?
Around 14 days post-infection.
125
How long can MERS viral RNA persist in severe disease?
Over 21 days.
126
MERS serology approach?
ELISA screening + confirmation by IFA and neutralization assays.
127
Why is MERS serology limited?
Transient/absent antibody responses in mild/subclinical cases.
128
SARS grew in which cell lines for isolation?
Vero E6 and fetal rhesus monkey kidney cells.
129
Most widely used and more sensitive SARS test?
RT-PCR.
130
SARS specimens where virus can be detected?
Upper/lower respiratory tract, blood, stool, urine.
131
SARS detection is most effective in which week?
Second week of illness.
132
When does SARS IgG appear?
Around 10 days after fever onset; nearly universal after 4 weeks in favorable outcomes.
133
SARS empiric therapies initially used?
Corticosteroids and ribavirin.
134
Ribavirin activity against SARS-CoV (in vitro)?
Little in vitro activity.
135
Possible effect of corticosteroids in SARS?
May have worsened outcomes.
136
Other agents used in some SARS cases (evidence unclear)?
Lopinavir-ritonavir and IVIG.
137
Interferon therapy in SARS (evidence type)?
Anecdotal evidence for benefit (IFN-α or IFN-β).
138
Current proven effective antiviral treatment for SARS?
None; therapy largely supportive.
139
Current main treatment for MERS?
Supportive measures; no antiviral drugs recommended.
140
MERS-CoV sensitivity to interferon vs SARS-CoV?
MERS-CoV appears more sensitive to IFN-α/IFN-β.
141
Interferon alfa-2b + ribavirin for MERS (reported outcome timing)?
Inhibited in vitro; improved outcomes at 14 days but not at 28 days.
142
GS-5734 has shown activity against which viruses?
SARS-CoV and MERS-CoV (cell culture and experimental animals).
143
In MERS, what infection control precautions are recommended?
Standard droplet precautions; aerosol precautions during high-risk procedures.
infecto
flashcards
Decks in class (19)
# Cards
-
rhinovirus106
-
adenovirus118
-
Coronavirus143
-
influenza48
-
parainfluenza83
-
Respiratory syncytial virus67
-
Streptococcus pneumoniae116
-
moraxella44
-
haemophilus influenzae59
-
mycoplasma pneumoniae91
-
rotavirus43
-
E. coli54
-
salmonella45
-
cholera43
-
shigella and EIEC42
-
Entamoeba47
-
yersinia47
-
campylobacter51
-
helicobacter76
