Micb 202: Virology - Chapter 2B - Orthomyxoviruses

Front 1

What does the genome of all orthomyxoviruses look like?

Back 1

segmented (-)strand RNA genome

Front 2

How many genera in the family Orthomyxoviruses? What is this based on?

Back 2

2 (Influenza A/B, Influenza C)
antigenic differences
structural proteins

Front 3

Do orthomyxoviruses encode and package thier own polymerase?

Back 3

yes

Front 4

Where does the transcription and recplication of the genome occur for Orthomyxoviruses?

Back 4

nucleus of host

Front 5

Where do Orthomyxoviruses uncoat?

Back 5

inside the host cell

Front 6

T/F: Influenza A and B are morphologically distinguishable

Back 6

F

Front 7

How are influenza viruses typically transmitted?

Back 7

respiratory route

Front 8

Describe the Influenza A/B genome

Back 8

8 segments of ss(-)RNA

Front 9

Describe the Influenza C genome

Back 9

7 segments of ss(-)RNA

Front 10

__ of the Influenza A/B genome segments code for ___ protein(s). The other ___ code for two proteins.

Back 10

six
one
two

Front 11

What are the genome segments of Influenza A/B called?

Back 11

RNPs

Front 12

How many amino acids does NP bind?

Back 12

~20

Front 13

What is the most common protein in the RNPs?

Back 13

nucleoprotein

Front 14

What does the Influenza A/B RNA polymerase complex consist of?

Back 14

PB1, PB2, PA

Front 15

What are the four different proteins in each RNP?

Back 15

NP
PB1
PB2
PBA

Front 16

What is Influenza A/B's morphology?

Back 16

highly pleomorphic
commonly spherical or ovoid
80-120 nm in diameter
enveloped with viral glycoproteins embedded

Front 17

Is Influenza A/B enveloped?

Back 17

yes

Front 18

how big is Influenza A/B ?

Back 18

80-120 nm in diameter

Front 19

What are the two types of glycoproteins in the lipid envelope of Influenza A/B ?

Back 19

Hemagglutinin (HA)
Neuraminidase (NA)

Front 20

What is the structure and function of HA?

Back 20

trimer of identical subunits
used in attachment

Front 21

What is the structure and function of NA?

Back 21

tetramer of identical subunits
used in detachment

Front 22

There are about ___ copies of the glycoproteins in the lipid enveloped of Influenza A

Back 22

500

Front 23

There are approximately ___ HA to every NA

Back 23

5

Front 24

What does HA do to red blood cells?

Back 24

agglutinates them

Front 25

In the lipid envelope there is an ion channel protein called ___, which is involed in the uncoating process

Back 25

M2

Front 26

The ___ (__) protein lines the inside of the lipid envelope

Back 26

matrix (M1)

Front 27

What is the most abundant Influenza A/B viral protein?

Back 27

M1

Front 28

What is the function of M1?

Back 28

allows the nucleocapsid, envelope, and glycoproteins to assemble correctly

Front 29

What is the Influenza A host range?

Back 29

humans, animals, birds (pigs and birds particularly important reservoirs)

Front 30

What is the Influenza B host range?

Back 30

only humans

Front 31

What is the Influenza C host range?

Back 31

only humans

Front 32

Does Influenza C cause disease?

Back 32

it is not thought to

Front 33

What is the host cell receptor for influenza virus?

Back 33

N-acetylneuraminic acid (NANA or sialic acid) residues on mucoproteins

Front 34

Where is NANA located?

Back 34

on mucoproteins

Front 35

What is the natural habitat forinfluenza virus ?

Back 35

URT

Front 36

What is the first step in influenza virus replication cycle?

Back 36

HA cleaved extracellularly by the protease "tryptase Clara"

Front 37

Where does tryptase Clara come from?

Back 37

Clara cells of the bronchiolar epithelial cells

Front 38

What activates the HA, so that it can bind to NANA residues?

Back 38

cleavage by tryptase Clara

Front 39

HA binding to NANA residues is thought to be high affinity (T/F)

Back 39

F. It is thought to be low affinity, but high avidity because of multiple weak interactions

Front 40

The influenza virus enters the cell by invagination of the plasma membrane to form ___-coated pits. What is this process called?

Back 40

clathrin
receptor-mediated endocytosis

Front 41

What happens after the clathrin coat is removed, during invasion of host cell by influenza virus?

Back 41

vesicle fuses with an endosome (which has low pH)

Front 42

What does exposure to low pH trigger, during invasion of host cell by influenza virus?

Back 42

a second conformational change in HA, allowing envelope of the virus to fuse with the membrane of the endosome

Front 43

The second conformational change in HA leads to what? What triggers this process?

Back 43

release of the genome segments into the cytoplasm

the low pH inside the endosome

Front 44

How do the released RNPs enter the nucleus, during invasion of host cell by influenza virus?

Back 44

specific targeting sequences in the NP protein allow entry through the nuclear pore

Front 45

Where is viral mRNA synthesized, during invasion of host cell by influenza virus?

Back 45

in the nucleus

Front 46

What are used as primers during synthesis of the viral mRNA, during invasion of host cell by influenza virus?

Back 46

the capped 5' ends of the host cell pre-mRNAs and mRNAs

Front 47

During mRNA synthesis, influenza virus uses the cellular RNA polymerase (T/F)

Back 47

F. It has its own.

Front 48

Describe the process of "Cap Stealing" employed by influenza virus

Back 48

The viral RNA polymerase complex attaches to the 5' end of cellular mRNA. It then degrades everything but the 5' cap and about 13 nucleotides

Front 49

The viral RNA polymerase complex synthesizes the (_) strand using the (_) strand as template, adding the complementary nucleotides to the "stolen cap"

Back 49

(+)
(-)

Front 50

The RNA polymerase complex read the (-) strand in the __->__ direction while synthesizing in the __->__ direction

Back 50

3'->5'
5'->3'

Front 51

What is the approximate difference in length between viral mRNA and full-length RNA, during invasion of host cell by influenza virus?

Back 51

15-22 nucleotides

Front 52

Why is the viral mRNA shorter than the full RNA, during invasion of host cell by influenza virus?

Back 52

the viral (-) strang has a 'panhandle' structure at the 5' end that functions as a terminator

Front 53

What are the two advantages of the cap-stealing method employed by influenza?

Back 53

mRNA produced can be translated by cellular ribosomes (because it has the h' methylated cap and the poly-A tail)

host cell mRNA is degraded (less competition for ribosomes)

Front 54

T/F: none of the influenza mRNAs need to be sliced

Back 54

F. some do need splicing in the cytoplasm

Front 55

The viral mRNAs that specify viral ___ proteins are translated by the ER-bound ribosomes, whereas all the other mRNAs are translated by cytoplasmic ribosomes

Back 55

envelope

Front 56

Where are newly synthesized PA, pB1, PB2 and NP proteins transported to?

Back 56

nucleus

Front 57

What is the function of newly synthesized PA, pB1, PB2 in the nucleus?

Back 57

they catalyze synthesis of the genomes for progeny

(+) strands are made first, then (-) strands are made from these

Front 58

What causes the cessation of viral mRNA synthesis and induces export of the progeny nucleocapsids into the cytoplasm?

Back 58

binding of M1 to newly snythesized (-) RNA

Front 59

What results from M1 binding the newly synthesized (-) strand RNA inside the nucleus?

Back 59

transport of progeny nucleocapsids into the cytoplasm

Front 60

Which proteins are transported to the cell surface, to become incorporated into the plasma membrane?

Back 60

HA and NA

Front 61

The virion nucleocapsids associate with the __ proteins and the ___ protein and are transported to the cell membrane to associate with the spike proteins

Back 61

M1
NS2

Front 62

T/F: Influenza lyses the cell to escape

Back 62

F. It buds off

Front 63

What is the exact function of NA during exit of influenza?

Back 63

remove the sialic residues from surface of infected cell to free the virus particle

Front 64

replication and transcription is done in the ___ and translation is done in the ___ during influenza invasion

Back 64

nucleus
cytoplasm

Front 65

For an influenza virus to be infectious, it must have one copy of each segment (T/F)

Back 65

T

Front 66

What causes the HA fusion peptides to insert in the endosomal membrane during the first stages of invasion by influenza virus? What results?

Back 66

acidity of endosome
dissociation of RNPs from M1, release of RNPs

Front 67

Does the synthesis of a complete (+) strand (to use as template for (-) strand) involve the RNA polymerase complex?

Back 67

yes

Front 68

Does creation of the full-length (+) RNA template involve cap-stealing?

Back 68

no

Front 69

What may regulate the switch to full-size (+) RNA production?

Back 69

amount of 'free' NP present

Front 70

T/F: The RNA polymerase complex seems to 'acquire' the ability to initiate RNA synthesis without a primer

Back 70

T

Front 71

T/F: Influenza can be spread by direct contact

Back 71

T

Front 72

Why are influenza virus infections usually limited to URT?

Back 72

this is the only location where Clara cells are found

Front 73

How long does the acute respiratoy illness last (influenza)?

Back 73

3-7 days

Front 74

What is the common cause of death during influenza infection?

Back 74

opportunistic pathogen such as Hemophilus influenzae or Staphylococcus aureus

Front 75

Influenza is shed in high amounts about __ hours after infection

Back 75

48

Front 76

What is the influenza naming convention?

Back 76

A/USSR/strain#/year of isolation (H_N_)

Front 77

HA and NA glycoproteins can change in two ways, what are these?

Back 77

antigenic drift
antigenic shift

Front 78

Define antigenic drift

Back 78

minor changes due to accumulation mutations (caused by lack of proof-reading in RNA polymerase)

Front 79

Define antigenic shift

Back 79

genetic reassorment of two or more viruses that have simultaneously infected the same cell

Front 80

How is influenza virus cultivated for vaccine production?

Back 80

embryonic hen eggs

Front 81

How are new vaccines produced?

Back 81

genetic reassortment to produce strain with desired HA/NA antigens

Front 82

How is the virus inactived during vaccine production (influenza)?

Back 82

formaldehyde

Front 83

What are the three vaccines for influenza currently in use?

Back 83

whole (inactived)
subvirion (purified virus treated with detergent to solubilize envelope)
surface antigen (isolated HA and NA glycoproteins)

Front 84

Where are the epitopes found in influenza virus?

Back 84

the HA and NA proteins

Front 85

What is the main approach in terms of antiviral drugs for influenza?

Back 85

NA inhibitors: (Oseltamivir (Tamiflu), Zanamivir (Relenza) and GS 4104

effective for A and B