Session *7 Medical Virology

Front 1

Two Respiratory Viruses are _____ and ____.

Back 1

SARS and Influenza

Front 2

What do living cells do to make easier entry sites for pathogens?

Back 2

They absorb nutrients, facilitate gas exchange, and release wastes

Front 3

The average individual ingests about ____ microorganisms per day or _____ per minute.

Back 3

10,000

8

Front 4

What 4 conditions must be met before respiratory disease can be established?

Back 4

1. sufficient dose of agent inhaled
2. Infectious particles must be airborne
3. Infectious organism must be alive and viable in the air
4. The organism must be deposited on susceptible tissue on the host

Front 5

How many colds per year?

Back 5

65 million

Front 6

Respiratory diseases

Family: orthomyxoviridae
Genus: ______

Back 6

Influenza

Front 7

Respiratory diseases

Family: paramyxoviridae
Genus: ______

Back 7

Paramyxovirus

Front 8

Respiratory diseases

Family: Pnuemovirus
Genus: ______

Back 8

Respiratory Synctial Virus

Front 9

Respiratory diseases

Family: Picornoviridae
Genus: ______

Back 9

Enterovirus

Front 10

Respiratory diseases

Family: Herpesvirus
Genus: ______

Back 10

Rhinovirus
Herpes Virus
Varicella-Zoster Virus

Front 11

Why are children tend to get sick (respiratory) more often?

Back 11

They interact more with each other

Front 12

Why do enteroviruses seem to have outbreaks in May - Aug?

Back 12

Enteroviruses may be related to swimming pools

Front 13

Why do you suppose there are outbreaks of rhinovirus and parainfluenza in March -April?

Back 13

People are inside more

Front 14

True or False

Influenza tends to be more transmissible at lower temps with low humidity and at higher temps with higher humidity

Back 14

True

Front 15

Influenza virus particles tend to be more/less stable at higher humidty and more/less stable at lower humidity.

Back 15

more
less

Front 16

Influenza virus particles tend to be more/less stable at higher temperatures and more/less stable at lower temperatures

Back 16

less
more

Front 17

Why do influenza particles tend to have less stability in higher humidty?

Back 17

They get stuck to water droplets and fall to the ground before they get inhaled

Front 18

Distinct difference between viral and bacterial pathogenesis?

Back 18

Viral: Multiplication within cell = exudate

Bacterial: Multiplication occurs in exteriour of cell = adherent exudate (from toxins and enzymes)

Front 19

Virus spread can occur in what two ways?

Back 19

Local --> adjacent spread
Directional --> to where the infection started

Front 20

List viruses that are apical in directionality.

Back 20

Rhinovirus, influenza, and polio

Front 21

List viruses that spread basolaterally in direction.

Back 21

VSV (vesicular stomatitis)

Front 22

Influenza virus causes a(n) ____ infection.

Back 22

Acute

Front 23

Give the steps of acute infection in a host.

Back 23

1. Rapid Rise in Virus
2. Innate defenses
3. Adaptavie Response
4. Clearing of the Virus
5. Protective Immunity

Front 24

Virus induced pathology (of acute infection) can be caused by the _____.

Back 24

host immune system

Front 25

Many symptoms (of acute infection) are due to a
________.

Back 25

vigorous host immune response

Front 26

Why does infection of internal organs cause considerable damage?

Back 26

Because infected cells are killed by both the virus and host immune response

Front 27

HRV 1st recovered _______
after infection.

Back 27

8 – 18 h

Front 28

Symptoms of HRV appear ______ after inoculation and include ________.

Back 28

10-12 h
Nasal obstruction (*)
‣ Fluid in nasal passages ( )
‣ Mucous in nasal passages
and sinuses
‣ Sore throat
‣ Sneezing and coughing

Front 29

Is the duraction of HRV relatively short or long?

Back 29

Shawty.

Front 30

Two Classes of Myxoviruses are ____ and _____ .

Back 30

Paramyxoviridae and Orthomyxoviridae

Front 31

What properties made myxoviruses one of the best studied viruses during
the 1940's?

Back 31

the characteristic property of haemagglutination and the fact that the virus could be propagated in embryonated hens eggs (after
cold-adaptation)

Front 32

-Haemagglutin- What is it?

Back 32

The ability to aggregate RBCs and made it easy to recognize when the virus was there

Front 33

Describe Influenza Type A

Back 33

moderate to severe illness
all age groups
humans and other animals

Front 34

Describe Influenza Tybe B

Back 34

milder epidemics
humans only
primarily affects children

Front 35

Describe Influenza Type C

Back 35

rarely reported in humans
! ! ! - no epidemics

Front 36

Which strain of Influenza has no epidemics?

Back 36

C

Front 37

What does the subtype of influenza represents?

How many hemas and neuras in the world?

Back 37

Subtype represents the type of Hem and type of Neur. – tells what types of cells its going to interact with and what types of antibodies its going to respond to

16 and 9

Front 38

Strain: A / Hong Kong / 1 / 68 (H3N2)

BREAK IT DOWN!

Back 38

Type:
A,B,C

Location of original isolate

Isolate number

Year of isolation

Subtype

Front 39

Incubation for influenza is ______ days with a range of _____.

Back 39

2 (1-5 days)

Front 40

Severity of illness due to influenza depends on

Back 40

prior experience with related variants.

similar strain- not to sick, new strain- more severe reaction

Front 41

Clinical symptoms of influenza include:

Back 41

Abrupt onset of fever, myalgia (muscle pain), sore throat, non-productive cough,
headache.

Front 42

True or False

Influenza can cause stomach problems.

Back 42

FALSE

Front 43

Replication of viral influenza generall occurs in ____ and can lead to ____.

Back 43

Respiratory epithelium - with possible subsequent destruction of cells.

✦this leads to increased access for pathogens
causing secondary infections

Front 44

True or False

Viremia of Influenza is detected

Back 44

FALSE

Front 45

With influenza- viral shedding generally occurs for _____.

Back 45

Viral shedding in respiratory secretions
for 5-10 days.

Front 46

List some influenza complications

Back 46

Pneumonia (w/primary from virus and secondary from bacteria)

Reyes syndrome (when asprin is used during viral infection)

Myocarditis

Hospitalization

DEATH!!!

Front 47

How many hospitilizations per year due to influenza?

Back 47

100,000

Front 48

How many deaths per year due to influenza

Back 48

.5-1/1000
or 30,000/year in North America

Front 49

Reservoir for Influenza?

Back 49

Animals or Human (TYPE A ONLY)

Front 50

Transmission for Influenza?

Back 50

Respiratory or Fomite

Front 51

Communicability for Influenza?

Back 51

Maximum 1-2 days before
and up to 4-5 days after onset

Front 52

Peak month for influnza virus?

Back 52

December

Front 53

True or False

Influenza A illicts a strong immune response

Back 53

True

Front 54

Even through influenza illicts a strong immune response, it still circulates in humans..why?

Back 54

still circulates in humans because of constant mutation, strains change like crazy

Front 55

Structure: Influenza A virus

Back 55

Enveloped, (-) sense,
segmented (8), RNA virus

Draw it (see desktop: Influenza)

Front 56

Influenza virus infection cycle- what happens in the nucleus?

Back 56

mRNA
transcription, genome
replication, and new
RNP formation occurs

Front 57

Influenza virus infection cycle- what happens in the cytoplasm?

Back 57

New virion assembly
and budding

Front 58

Why is it weird that mRNAs are capped and polyadenylated in the influenza virus and the genome/antigenome
are not capped or
polyadenylated ?

Back 58

Unusual among RNA viruses because all viral
RNA synthesis occurs in nucleus

Front 59

Influenza has 8 ORFs and produces
at least 11 unique proteins!
How is this?

Back 59

Variety of genome expression strategies:
• RNA splicing.
• Overlapping ORFs with leaky scanning.

Front 60

Which RNA's in influenza produce 2 proteins?

Back 60

1,7,8

Front 61

RNA segment 1 makes what proteins?

What do these proteins do?

Back 61

PB1, PB1-F2

Apoptosis

Front 62

RNA segment 7 makes what proteins?

Back 62

M1 AND M2

Front 63

RNA SEGMENT 8 MAKES WHAT PROTEINS?

What do these proteins do?

Back 63

NS1 and NS2 (AKA NEP)

mediate nuclear export of RNP

Front 64

How does segment 1 fit two proteins in?

Back 64

Overlapping ORFs + leaky
scanning:

Front 65

PB1-F2:

Back 65

mitochondria killer!

Front 66

PB1:

Back 66

binds 5` termini of
genome and activates capbinding
capacity of viral RdRp.

Front 67

NS1:

Back 67

NS1 -> full length: inhibits splicing & polyadenylation
of host mRNA.

Saves Energy for evil bidding

Front 68

NS2

Back 68

binds M1 to facilitate RNP export from the nucleus

Front 69

The influenza genome does not
code for _____

Back 69

the cap structures
that attract ribosomes - needs host help

Front 70

Describe "cap snatching"

Back 70

Cap structures and a few
bases are cleaved from the
5’ ends of random cellular
nuclear mRNAs.
G residue is added to
the cap by viral RdRp.
cap serves as a primer for
mRNA synthesis

Elongation of the viral mRNA

Front 71

Functions of cap snatching:

Back 71

Primes viral mRNA synthesis.

Shuts down host cell protein synthesis.

Front 72

What is the most abundant viral protein in influenza infected cells?

Back 72

NS1

Front 73

Other functions of NS1?

Back 73

binds dsRNA replication intermediates, to
prevent a PKR-mediated interferon response.

binds eukaryotic elongation factor 4G1 !
(eELF4G1), recruiting it to viral mRNA and increasing translation by ribosomes.

inhibits cellular mRNA synthesis

Front 74

Ways NS1 stops cellular mRNA synthesis

Back 74

Inhibiting 3’ end processing of host mRNA.
- Inhibits cleavage of 3’ end of cellular pre mRNA
prior to addition of the poly-A tail.
- Binds cellular poly-A binding protein (PAB2),
preventing its association with cellular mRNA poly-A
tails and export of cellular mRNA from the nucleus.

Front 75

How does influenza cap snatchin work and why does it do this?

Back 75

Influenza cap snatching "cuts" off the cap from cellular mRNA and it does this to save energry from cellular mRNA production for host mRNA production

Front 76

mRNA to genomic RNA is regulated by ____.

Back 76

Free nucleocapsid protein molecules and the axquisition of RdRp.

Front 77

Np binds to the _____ strands.

Back 77

+

Front 78

Which proteins (of influenza) are associated with translation on the ribosomes and later with the ER?

Back 78

HA, N, M2

Front 79

____ is imported to the nucleus and associates with the new RNPs.

Back 79

M1

Front 80

What is HAo translated by?

Back 80

By ER ribosomes and then trimerizes in the ER.

Front 81

Where does the HAo go after its little visit with the ER?

Back 81

It goes to the Golgi

Front 82

What happens to HA0 in the Golgi?

Back 82

It is glycosylated and cleaved by cellular serine protease-

It becomes the mature HA1 and HA2

Front 83

Cleavage of _____ is essential to produce an infectious virion (influenza)

Back 83

HAo

Front 84

What prevents progeny virions from reinfecting the same cell or aggregating with each other?

Back 84

Neuraminidase

Front 85

How many active sites are there for sialic acid cleavage?

Back 85

4

Front 86

Define Tropism

Back 86

A predilection for viruses to infect certain tissues and not others.

Front 87

Tropism dependent upon:

Back 87

Appropriate expression of
cellular receptor.
★ Cellular proteins that regulate
viral transcription.
★ Cell proteases.
★ Accessibility to susceptible
cells.

Front 88

Define antigenic drift

Back 88

small and accumulated changes in the
genome of the virus

Front 89

Give some details of antigenic drift.

Back 89

-Gradual process that results in a slightly different strain of the virus
that we have poor immunity against.
-This is why you need yearly influenza vaccinations!

Front 90

Define antigenic shift

Back 90

result of reassortment of virus genome
segments in humans, pigs and birds (no immunity against)

Front 91

True or False
Antigenic Shift are rare events that lead entirely to novel genes from other animal influenza shifting into a human influenza virus

Back 91

True

Front 92

How can antigenic shifts lead to pandemic strains?

Back 92

Introduction into a naive human immune system with increased virulent strain resulting.

Front 93

Antigenic drift is due to point mutations in what genes?

Back 93

HA and NA genes.

Front 94

With antigenic shift, is it possible to have effective long term vaccination?

Back 94

No- because of a gradual selection of novel antigenic variants due to natural selection

Front 95

H3N1 initially infected ____
but in 2004 jumped
species, infecting &
killing ____.

Back 95

horses then dogs

Front 96

Hosts for influenza all started with what animal?

Back 96

fowl

Front 97

What two criteria define influenza A?

Back 97

Infection must spread throughout the world.
2. HA of the virus must not cross-react with antibodies
to HAs of previously circulating influenza A viruses.

Front 98

Influenza pandemics can occur by:

Back 98

1. Very strong antigenic drift viruses (mutation of a
very few, but antigenically distinct and functionally
important amino acids in HA).
2. Antigenic shift.
3. Reintroduction of a previously circulating virus into a
population (generation) never exposed to it.
4. Introduction of the virus from another animal
species.

Front 99

True or False
Antigenic shift and antigenic drift
have both caused pandemics

Back 99

True

Front 100

Avian flu infecting
people are ____ and ____

Back 100

H5N1 & H7N7

Front 101

Segment Reassortments occur in what animal?

Back 101

SWINE

Front 102

Swine have ___ and ___ sialic
acid residue linkages on the
surface cells in the trachea.

Back 102

3' and 6'

Front 103

How does segment reassortment occur in swine?

Back 103

Mutation of a single amino acid in HA (E190D) confers switch from 3’to 6` linked sialic acid binding.

Front 104

Why aren’t successful reassortments (for influenza) more frequent?

Back 104

1.differences in protein/lipid glycosylation cause a species barrier

2. Human influenza viruses prefer to infect cells with
terminal sialic acid residues attached to the receptor via
6’-linkage wherease Avian and equine influenza viruses use 3’-linkages

*however swine have both 3 and 6' sialic linkages

Front 105

Avian Flu :H_N_

Back 105

H5N1

Front 106

List some general characteristics for why deaths occur due to avian flu

Back 106

deaths were due to viral infection, not secondary infections
“cytokine storm”
lymphopenia, ARDS, pneumonia

Front 107

How is avian flu transmissable?

Back 107

Transmission from direct contact with birds

H5N1 genome sequence indicates the virus was an avian strain that jumped species without antigenic shift

Front 108

Antiviral treatment of avian flu?

Back 108

Sensitive to NA inhibitors but not to
M2 channel blockers

Front 109

What two diseases are the result of antigenic shift?

Back 109

asian and hong kong flu

Front 110

Define cytokine storm

Back 110

A really, robust strong response that overwhelms the infected individuals leading to decrease in lymphocytes

Front 111

M2 ion blockers do not work for ___ flu

Back 111

avian

Front 112

Influenza pandemics are likely occur after what action?

Back 112

Pandemic is likely after virus adapts to permit efficient
person to person transmission

Front 113

What caused outbreaks of influenza in indonesia?

Back 113

migratory birds

Front 114

True or False

National borders help to restrict pandemics

Back 114

viruses don’t stop at national borders

Front 115

Influenza pandemics occur at what intervals?

Back 115

Irregular 10-50 year intervals

Front 116

Spanish flu

Back 116

1918 H1N1 (drift)

Front 117

Asian flu

Back 117

1956 H2N2 (shift)

Front 118

Hong Kong flu

Back 118

1967 H3N2 (shift)

Front 119

Spanish flu is the same subtype as what?

Back 119

Russian Flu

Front 120

This is also associated with influenza - think blue

Back 120

Cyanosis

Front 121

1918 Pandiemic characteristics

Back 121

Two waves of the virus in the US-March wave not as lethal; likely changes in strain increased
pathogenicity and virulence.

Peak of local outbreaks was reached in two weeks,
indicating each victim infected many persons.

High mortality among 15-35 year-olds.
✴ Result of “Cytokine storm” (reconstructed virus)

Front 122

Average of ___ years of life lost per person during the pandemic.

Back 122

15

Front 123

What killed more: influenza or WAR?

Back 123

Influenza

Front 124

What two types of influenza virus exist?

Back 124

Inactivated and attenuated

Front 125

Details about inactivated influenza vaccine?

Back 125

Isolated HA gives good protection (~60-80%).
✦ Vaccines are produced by reassortment of eggadapted
strains with strains with the !
required HA type.
✦ Produced in embryonated eggs (cheap and
efficient), purified and formalin inactivated.
✦ May contain thimerosal, a preservative that
contains mercury.
✦ Administered intramuscularly by injection.

Front 126

Details about attenuated influenza vaccine?

Back 126

Grown in embryonated eggs
✦ Administered intranasally by sprayer
✦ Licensed for use in 2003

Front 127

How many different strains of the virus are carried by the influenza vaccine?

Back 127

Three

A variation of A and B strains depending on which
are dominant for that season (this year we have 2 A
strains and a B).

Front 128

The vaccine production takes ___ months.

Back 128

6-9

Front 129

World Health Organization (WHO) recommended
replacing the _____ with a _____
strain of A/H1N1.

Back 129

New Caledonia strain
Solomon Islands

Front 130

Most years, experts manage to match their flu vaccine selections in
the ____to the strains that circulate later in the year throughout
the U.S. and globally.

Back 130

spring

Front 131

Influenza____typically makes up about 85% of all flu cases.

Back 131

A

Front 132

How the Vaccine is Made

Back 132

Each separate strain is injected through the
egg’s air sac, into the amniotic cavity directly
surrounding the chick (amniotic inoculation).
• Specialty chicken eggs are used to develop
the vaccine and cleaned with disinfectant.
• The eggs are then incubated for several days
to allow each virus to multiply.
The virus fluid then undergoes multiple
purification/inactivation steps to ensure each
virus is “killed”.
– chemically disruption of the virus.
• Viral fragments are then collected from each
of the grown strains and combined and tested
to ensure safety.
• The vaccine is administered via intramuscular
injection.

Front 133

Intranasal influenza vaccine is approved for what kind of people?

Back 133

healthy
people from 5 through 49 years of age, who are not
pregnant.

Front 134

Influenza Vaccine Adverse Reactions

Back 134

Local reactions!! 15%-20%
✴ Fever, malaise! ! uncommon
✴ Allergic reactions! rare
✴ Neurological ! ! very rare
reactions

Front 135

Influenza Vaccine:
Contraindications and Precautions

Back 135

Severe allergy to vaccine component (e.g.,
! egg, thimerosal) or following prior dose of
! vaccine.
 Moderate to severe acute illness.
 Immunosuppressed by medication or disease.

Front 136

Influenza Antiviral Agents

Back 136

Amantadine and rimantadine
• Effective against influenza A only.
• Believed to block M2 H+ ion channels.

Zanamivir (Glaxo Wellcome; inhaled powder)
and Tamiflu (Roche; oral oseltamivir)
• Both effective against influenza A and B
• Neuraminidase inhibitors.

Front 137

Etiological Agent of SARS

Back 137

Coronavirus

Front 138

SARS-CoV: Coronaviridae DESCRIBE!

Back 138

Enveloped with clubbedshaped
projections
Helical nucleocapsid
Most coronaviruses are
intestinal viruses!

Front 139

True or False

Coronovirus is the smallest (+)ssRNA genome

Back 139

False- its the largest

Front 140

ORF ___ is immediately
translated to make
viral polymerase in the coronavirus

Back 140

1a/1b

Front 141

Where does mRNA for genes 2-9 come from in the coronavirus?

Back 141

Nested subgenomic RNAs (sgRNA)
mRNA 2-9

Front 142

Where does coronavirus replication take place?

Back 142

All in the cytoplasm - review slide 93

Front 143

How many general generations are there in SARS transmission?

Back 143

4
INDEX CASE - first gen
2nd Gen - Close direct contact with health-care
workers (HCW) or others (family, visitors)

3rd gen-Family members of HCW
4th gen -Other contacts in
community

Front 144

How long after exposure do you get symptoms from SARS?

Back 144

3-7 days

Front 145

What are some symptoms of SARS?

Back 145

headache, sore throat, shortness of breath and difficulty breathing due to pneumonia, low white cell count, flu-like symptoms such as joint pain and malaise, fever, coughing

Front 146

True or False

SARS is difficult to distinguish from
other respiratory diseases
in early stages.

Back 146

True

Front 147

SARS: lung pathology

Back 147

Inflammatory exudation
in alveoli and
interstitial spaces.
 Monocyte and
lymphocyte infiltration
of lung tissue.
 Hyperplasia of alveolar
epithelial cells and
fibrous tissue.
 Fibrosis of lung tissue

Front 148

SARS: Cellular Pathology

Back 148

Diffuse but substantial
aveolar damage with
abundant macrophages
• Multinucleated
syncytial pulmonary
cells (1st description for
a coronavirus)

Front 149

In China, SARS mostly affects what age group?

Back 149

20s, but fatality is highest among those in 70s

Front 150

True or False

Antibiotics and antivirals appear reduce recovery time for SARS.

Back 150

FALSE-Antibiotics and antivirals appear to have no effect.

Front 151

Who is at great risk for contracting SARS?

Back 151

HCW's

Front 152

What animal goes hand in hand with SARS?

Back 152

palm civet-yum yum!

Front 153

Three stages in SARS evolution?

Back 153

Early phase (Nov 16, 2002-Jan 31, 2003): Viruses isolated from humans had identical
genetic fingerprints to those in animals such as civet cats, suggesting the virus had
jumped from animals to people.
Middle phase (Jan 31-Feb 21, 2003): More person-to-person infections. All viruses
had a common genetic fingerprint.
Late phase (after February 2003): SARS virus had fully adapted to humans.

Front 154

Why is it bad bring animals from different habitats together in regards to SARS?

Back 154

Bringing together
animals that don’t
naturally occupy
the same habitatmay promote
increased evolution(adaptation) of disease agents.

Front 155

Future SARS control?

Back 155

Continued case identification through surveillance.

Continued collaborative studies in Guangdong province to identify
animal reservoirs and risk factors for transmission to humans.

Continued strengthening of surveillance for influenza and other
emerging infectious diseases.