Core Ii Virology

Front 1

What sort of genome does poliovirus have?

Back 1

One ss(+)RNA linear genome

Front 2

Describe poliovirus' structure

Back 2

naked, icosahedral virion composed of 12 pentamers (180 subunits), with a single, ss(+)RNA genome

Front 3

What is the tissue tropism of poliovirus?

Back 3

Spinal cord
Intestines

Front 4

Describe poliovirus' adsorption

Back 4

Temperature-independent
Reversible
Requires electrostatic interaction with divalent cations

Front 5

Which protein is important for poliovirus penetration?

Back 5

VP4 with its terminal fatty acid possibly interacts with the cellular membrane

Front 6

Describe the efficiency of poliovirus uncoating

Back 6

Very inefficient (~2%)

Front 7

What is the eclipse period? Which viruses have an eclipse period?

Back 7

This is when the virus has infected the cell and the genome is present as free nucleic acids and is sensitive to nucleases. This is before replication has occured. Most viruses have an eclipse period.

Front 8

Where does poliovirus replicate its genome?

Back 8

cytoplasm

Front 9

How does poliovirus cause cell death?

Back 9

Poliovirus severely decreases cellular RNA and protein synthesis

Front 10

How does poliovirus release from the cell?

Back 10

All at once when the cell disintegrates

Front 11

What four protein types are encoded by poliovirus?

Back 11

1. inhibitors of cellular RNA and protein synthesis
2. RNA-dependent RNA polymerase
3. Structural virion proteins (VP0, VP1, VP3)
4. Protease

Front 12

How does poliovirus replicate its genome?

Back 12

An RNA-dependent RNA polymerase is released during the uncoating period and transcribes the ss(+)RNA into ss(-)RNA which, through a RI form, arise many more ss(+)RNA genomes.

Front 13

Describe the protein product and protein synthesis of poliovirus.

Back 13

The linear ss(+)RNA genome of poliovirus is polycistronic with one initiator. The polyprotein is then proteolytically cleaved into intermediate protein products and the final protein products.

Front 14

Which capsid proteins become poliovirus' capsule? What is this unit called? How many per pentamer? How many per virion?

Back 14

Poliovirus polycistronic linear ss(+)RNA produces VP0, VP1, and VP3, which form one protomer. 5 protomeres make one pentamer (15 VP subunits). 12 pentamers make 180 VP subunits in total.

Front 15

Describe the structure of influenza virion

Back 15

Influenza Virus:
Pleomorphic, enveloped virion with a 8 helical capsids surrounding 8 monocistronic ss(-)RNA segments

Front 16

Describe the genome of influenza virus

Back 16

Influenza Virus:
Pleomorphic, enveloped with 8 helical capsids surrounding 8 monocistronic ss(-)RNA segments

Front 17

What is the role of HA in influenza virus?

Back 17

HA binds to N-acetylneuraminic acid on cell membranes, stimulating endocytosis

Front 18

What is the role of NA in influenza virus?

Back 18

NA digests neuraminic acid from its own envelope during maturation and release to prevent binding of other virion HA proteins.

Front 19

How does influenza virus adsorb?

Back 19

HA binds to N-acetylneuraminic acid, stimulating endocytosis

Front 20

How does influenza virus penetrate?

Back 20

Lysosome fuses with endosome
Acidification and proteolysis reveals lipophilic region of HA
Lipophilic region inserts into endolysosome membrane

Front 21

How does influenza virus uncoat?

Back 21

Once the lipophilic region of HA has fused with the membrane of the acidified endolysosome, the viral envelope and endolysosome membrane fuse and the nucleocapsid is released into the cytoplasm.

Front 22

What occurs during the eclipse period of Influenza Virus infection?

Back 22

The virus undergoes primary transcription, where a packaged viral RNA-depended RNA polymerase creates 8 truncated monocistronic mRNAs with polyA tails, 1 from each ss(-)RNA segment.

Front 23

What happens during the synthesis period of Influenza Virus infection?

Back 23

Viral proteins are synthesized from the mRNA, creating structural (NA, HA, M) and non-structural (Polymerase) proteins.

Front 24

Which influenza virus proteins are synthesized on free ribosomes? Which are on ER-bound ribosomes? How are they distinguishable?

Back 24

M and capsid proteins are synthesized on free ribosomes since they are not glycosylated.
HA and NA are synthesized on ER-bound ribosomes since they are glycosylated.

Front 25

What happens during the replication period of Influenza Virus infection?

Back 25

Each ss(-)RNA is replicated into 8 full-length ss(+)RNA segments, from which a greater number of ss(-)RNA copy molecules are created.

Front 26

How does Influenza Virus mature?

Back 26

HA and NA proteins cluster on the cell membrane and exclude cellular proteins, M protein beneath attaches to HA and NA, and the nucleocapsid pushes out into the prepared membrane, creating a bud.

Front 27

Are there mature intracellular Influenza Viruses?

Back 27

No. All mature influenza viruses are extracellular, although the cell-associated virus particles are located on the cell surface.

Front 28

How does Influenza Virus release?

Back 28

Influenza Virus buds off of the cell and NA cleaves the neuraminic acid residues on its own envelope. Influenza viruses are continually released. There is not retention period.

Front 29

What is the effectiveness of the Sabin vaccine? What sort of vaccine is it? What are the benefits and the drawbacks of this vaccine?

Back 29

The Sabin vaccine is a live-attenuated vaccine. It is 90% effective, more cost-effective, does not require needles, and is given in patient-friendly droplet form, but it causes disease once every 2,000,000 vaccinations.

Front 30

What is the effectiveness of the Salk vaccine? What sort of vaccine is it? What are the beneftis and the drawbacks of this vaccine?

Back 30

The Salk vaccine is a killed vaccine. It is 70% effective, requires needles, and is more expensive, but it does not cause disease.

Front 31

What diseases do adenoviruses cause?

Back 31

Adenoviruses cause URT infections
Infants: pharyngitis, gastroenteritis
Military Recruits, Boarding students: Acute Respiratory Illness

Front 32

Describe the structure of adenoviruses

Back 32

Adenoviruses are naked, icosahedral viruses with a capsid comprised of hexons, pentons, and fibers protruding from the penton bases and have a single, linear dsDNA genome

Front 33

Describe the genome of adenoviruses

Back 33

Adenoviruses are naked, icosahedral viruses with a capsid comprised of hexons, pentons, and fibers protruding from the penton bases and have a single, linear dsDNA genome

Front 34

How are adenoviruses adsorbed?

Back 34

1. Fiber proteins interact with MHC I and the coxsackie-adenovirus receptor
2. The penton base binds to the integrin family of cell surface receptors, allowing internalization

Front 35

What are the receptors for adenoviruses?

Back 35

MHC I and the coxsackie-adenovirus receptor binds to the fiber protein in most cells
The integrin family of cell surface receptors binds to the penton base in fewer cells, allowing internalization

Front 36

Which interaction is necessary for RME of adenovirus?

Back 36

The penton base must bind to the integrin family of cell surface receptors

Front 37

Where does adenovirus localize to after uncoating? How does this occur?

Back 37

Penetration: RME and rupture of the endosome
Uncoating: release of core into the cytoplasm
Transport: the adenovirus core links to dynein motors and goes to the nuclear pore

Front 38

What are the three phases of adenovirus gene expression?

Back 38

Immediate early: E1A promotes survival
Early: vDNA Pol, pTP, ssDNA BP
Late: Structural proteins

Front 39

What occurs during the first phase of adenovirus gene expression? What is this phase called?

Back 39

Immediate early: E1A protein is produced which alters cellular growth properties to favor virus survival and proliferation, prepares for subsequent phase gene expression, and inhibits MHC I expression and IFN-b signalling

Front 40

Which genes are expressed during the second phase of adenovirus gene expression? What is this phase called?

Back 40

Early: vDNA Pol, pTP, and ssDNA BP are expressed

Front 41

In which virus was alternative splicing discovered?

Back 41

Adenovirus

Front 42

How does adenovirus increase the protein products from its limited genome? What sort of genome is it?

Back 42

Adenovirus has a single, linear dsDNA genome which can undergo alternative splicing when transcribed

Front 43

Where does DNA replication of adenovirus occur?

Back 43

In the nucleus

Front 44

What acts as a primer for the synthesis of nascent adenovirus DNA?

Back 44

pTP binds to dCTP, forming pTP-dCMP

Front 45

Once adenovirus DNA is being replicated, which genes are expressed?

Back 45

Late: structural proteins

Front 46

What occurs during the third phase of adenovirus gene expression? What is this phase called?

Back 46

Late: Structural proteins

Front 47

How and where does adenovirus mature and accumulate?

Back 47

Monomers form hexons and pentons in the cytoplasm and are transported to the nucleus.
The pentons and hexons form empty capsids.
The core, containing genomic dsDNA and associated proteins, is formed in the nucleus inserted into the capsid, creating a mature viral particle. These mature virus particles accumulate in the nucleus.

Front 48

How is adenovirus released?

Back 48

Viral particles accumulate in the nucleus and eventually cause cell death

Front 49

What is the normal pathway of interferon signalling? How does adenovrius inhibit this pathway?

Back 49

Normally, IFN-b causes a rapid, transient activation to an anti-viral state leading to the production of viral-activated Protein Kinase R (PKr) and RNAse L which degrades viral RNA.
Adenovirus IE protein product E1A blocks the IFN-b signalling pathway. Adenovirus VA RNA blocks PKr.

Front 50

How does adenovirus evade the immune system?

Back 50

1. inhibition of interferon signalling
-E1A blocks signal transduction
-VA RNA blocks PKr
2. Inhibition of Antigen presentation
-E1A suppresses MHC I gene expression
-E3 retains MHC I molecules in the ER

Front 51

How are viral antigens normally presented? How does adenovirus inhibit this pathway?

Back 51

Adenovirus protein product E3 retains MHC I in the ER
Adenovirus protein product E1A inhibits expression of the MHC I gene

Front 52

How are the two forms of immunity important in clearing adenovirus infection?

Back 52

Antibodies are important for resolution
Cell-mediated immunity is important for limiting outgrowth

Front 53

What is the tissue tropism of parvovirus?

Back 53

Erythrocytes

Front 54

Into which cells does parvovirus adsorb and how?

Back 54

Parvovirus binds to the P antigen on erythrocytes

Front 55

Describe the structure of parvovirus

Back 55

Parvovirus is a small, naked, icosahedral virus with a single linear ssDNA genome

Front 56

How many genes does parvovirus encode for? What are they classified into?

Back 56

1-2 nonstructural proteins (NS)
1-3 structural proteins (CAP)

Front 57

What sort of cell cycle is necessary for parvovirus replication?

Back 57

S phase

Front 58

Where does parvovirus replicate?

Back 58

In the nucleus

Front 59

Where are parvovirus proteins produced?

Back 59

Parovirus proteins NS and CAP are produced in the cytoplasm

Front 60

How does parvovirus replicate?

Back 60

Parvovirus ssDNA is copied into a dsDNA intermediate from which ssDNA copies are made

Front 61

How does parvovirus mature?

Back 61

Parvovirus CAP and NS proteins are made in the cytoplasm and ssDNA genomes are made in the nucleus. The ssDNA genomes are translocated out of the nucleus and assemble with the CAP and NS proteins to become new, naked viral particles.

Front 62

How is parvovirus released?

Back 62

The infected cell is lysed and parvovirus particles are released

Front 63

What disease does parvovirus B19 cause?

Back 63

5th disease

Front 64

What is a biphasic disease? Which virus is associated with it?

Back 64

Parvovirus causes a biphasic disease.
Phase 1 is associated with viremia and causes influenza-like symptoms and halting of erythrocyte production. It is mediated by antibodies.
Phase 2 is immune-related and caused by the deposition of immune complexes in the skin, leading to a lacy, red, maculopapular rash on the trunk and limbs and a slapped-cheek appearance.

Front 65

When is Parvovirus B19 no longer infectious?

Back 65

During the rash period, when the virus titer is low.

Front 66

Describe the structure of herpes viruses.

Back 66

Herpes viruses contain an envelope with glycoproteins, an amorphous protein-rich tegument, an icosahedral capsid, and a toroidal core with a large dsDNA genome wrapped around protein.

Front 67

Describe the genome of herpes viruses.

Back 67

Herpes viruses are made up of an envelope with glycoproteins, an amorphous protein-rich tegument, an icosahedral capsid, and a toroidal core with a large dsDNA genome wrapped around protein.

Front 68

How are herpes viruses able to circularize their genome?

Back 68

With inverted repeats

Front 69

How does herpes virus adsorb?

Back 69

Herpes virus envelope glycoproteins bind to unknown different surface receptors on different cells

Front 70

How does herpes virus penetrate?

Back 70

Interaction of envelope glycoproteins and cellular receptors results in direct fusion of the viral envelope with the cell membrane.

Front 71

How does herpes virus uncoat? Where does the capsid localize to?

Back 71

Once the evenelope glycoprotein and cellular receptor interactions cause envelope and cell membrane fusion, the capsid is released into the cytoplasm. The capsid localizes to the nuclue via a nuclear pore

Front 72

Where does herpes virus genome localize to? What happens to the genome once it gets there?

Back 72

Herpes virus genome localizes to the nucleus, where it circularizes.

Front 73

What protein transcribes herpes virus genes? Is it cellular or viral

Back 73

Cellular RNA Polymerase II transcribes herpes virus genes

Front 74

What are the three phases of herpes virus gene expression? What do they produce?

Back 74

alpha - immediate early: viral factors
beta - early: functional proteins
gamma - late: structural proteins

Front 75

How does herpes virus replicate?

Back 75

Viral DNA polymerase starts at one of three potential origins of replication and first does bi-directional replication and then does rolling circle replication

Front 76

Which virus does bi-directional replication and then rolling replication?

Back 76

Herpes virus

Front 77

What does rolling replication create? Where and how are these packaged?

Back 77

Herpes virus rolling replication produces high m.w. concatenated genomes which are cleaved from eachother and packaged into their own capsid in the nucleus.

Front 78

Which phase produces herpes virus structural proteins? Where do these go?

Back 78

gamma phase (late) structural proteins go into the nucleus

Front 79

How does herpes virus mature?

Back 79

Genomes are placed into capsids in the nucleus.
Nucleocapsids move to the cytoplasm and are surrounded by tegument proteins, and these bud off into virus-modified portions of the cell membrane.

Front 80

How does herpes virus release?

Back 80

The buds containing the external membrane glycoproteins surrounding tegument surrounding nucleocapsid pinch off and release

Front 81

What is latency? Which viruses have a latent period?

Back 81

Latency is a silent phase of infection which herpes viruses undergo.

Front 82

Where does VZV reside during its latent phase?

Back 82

Within the dorsal root ganglia

Front 83

Where does HSV-1 reside during its latent phase?

Back 83

Within the trigeminal ganglia

Front 84

Where does HSV-2 reside during its latent phase?

Back 84

Within the sacral ganglia

Front 85

Where do EBV and HHV8 reside during their latent phase?

Back 85

B lymphocytes

Front 86

Where does CMV reside during its latent phase?

Back 86

T cells and macrophages

Front 87

How is the herpes virus genome maintained during latency? What is expressed?

Back 87

As an unintegrated episome which expresses Latency Associated Transcripts (LAT) required for maintenance of latency

Front 88

What can cause reactivation of herpes virus?

Back 88

UV light/Sunshine
Immune suppression
fever
trauma to infected nerve cells
pneumococcal pneumonia
stress

Front 89

Which virus is associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and oral hairy leukoplakia?

Back 89

EBV

Front 90

Which viruses are associated with Kaposi's Sarcoma?

Back 90

CMV
HHV8
HIV

Front 91

Cell-mediated and humoral immunities are important for clearance of which herpes viruses?

Back 91

HSV1 and HSV2

Front 92

Cell-mediated immunity is important for clearance of which herpes viruses?

Back 92

VZV, EBV, CMV

Front 93

Describe the structure of HIV virus.

Back 93

Envelope surrounding matrix surrounding capsid containing 2 ssRNA genomes (diploid) wrapped around a core.

Front 94

Describe the genome of HIV virus.

Back 94

Envelope surrounding matrix surrounding capsid containing 2 ssRNA genomes (diploid) wrapped around a core.

Front 95

What are the three major gene categories of HIV? What does each code for?

Back 95

Gag - Structural proteins (MA matrix, CA contains capsid, NC binds RNA)
Pol - enzymes (PR protease, RT reverse transcriptase, IN integrase)
Env - fusion protein (SU surface blob, TM transmembrane anchor)

Front 96

What are the gene products of HIV Gag? How are they coded?

Back 96

Normal transcription produces the Gag transcript, which contains:
MA - matrix protein
CA - capsid protein
NC - RNA binding core protein

Front 97

What are the gene products of HIV Pol? How are they coded?

Back 97

Frameshifting produces the Pol transcript, which contains:
PR - protease
RT - reverse transcriptase
IN - integrase

Front 98

What are the gene products of HIV Env? How are they coded?

Back 98

Alternative splicing produces the Env transcript, which contains:
SU - surface blob binds to CD4 + CCR5 + CXCR4
TM - transmembrane anchor holds membranes together
Env exists as a trimer

Front 99

What are the functions of the 5' and 3' LTR?

Back 99

5' LTR: promoter
3' LTR: PolyA Signal

Front 100

What is the function of psi in the HIV genome?

Back 100

Packaging signal recognized by Gag NC protein

Front 101

How does T cell activation promote transcription of the HIV-1 provirus?

Back 101

T cell activation activates NFkB, for which there is a receptor in the 5' LTR of HIV-1

Front 102

How does HIV attach and penetrate into cells?

Back 102

HIV Gp120 on Env-SU binds to CD4, exposing the V3 loop which binds to CCR5 or CXCR4. V3 binding to CCR5 and CXCR4 allows the lipophilic anchor sequence to insert into the cell membrane.

Front 103

How does HIV uncoat?

Back 103

Once Gp120 has bound to both CD4 and CCR5/CXCR4, the hydrophobic anchor region of Env inserts into the cell membrane, promoting fusion of the membranes.

Front 104

How does HIV virus copy its genetic material?

Back 104

The ssRNA genome of HIV virus is primed by tRNA on the "primer binding site" which then allows reverse transcriptase to produce one complementary DNA molecule.
RNAse H degrades the leftover RNA except for a small segment at PPT which primes reverse transcriptase to make a second DNA molecule.

Front 105

How does HIV virus insert itself into the genome?

Back 105

Integrase trims 2 bases off the ends of the reverse transcribed dsDNA HIV genome and makes nicks in chromosomal DNA 5bp apart. Integrase ligates the viral DNA and cellular DNA repair mechanisms fill in the gap creating flanking 5bp segments.

Front 106

Which portions of genomes does HIV favor?

Back 106

Actively transcribed areas

Front 107

How does HIV virus replicate, assemble, and release?

Back 107

The HIV provirus DNA within the chromosome is transcribed to produce ssRNA genomes and Gag, Gag-Pol, and Env transcripts.
Gag and Gag-Pol localize to the cytoplasmic side of the membrane.
Env transmembrane proteins multimerize above the matrix proteins and bud off.
The nucleocapsid is added and the virus particle is released but is not yet mature.

Front 108

How does HIV virus mature?

Back 108

Once the virus particle is released it activates proteases which cleave the polyproteins, creating a mature virus particle.

Front 109

XMRV is associated with which diseases

Back 109

prostate cancer
chronic fatigue syndrome

Front 110

How are retroviral vectors used for gene therapy?

Back 110

The 5', 3' LTR and psi regions are left in the viral genome but Gag, Pol and Env are replaced with 1-2 target genes. These are formed into virus particles with chromosomally produced Gag, Pol and Env products, creating one-shot delivery vectors that are replication incompetent but are capable of integrating their genome into the host DNA.

Front 111

What is one of the drawbacks of retroviral gene therapy?

Back 111

Insertional oncogenesis can lead to T cell leukemia

Front 112

How does measles virus suppress the immune system?

Back 112

Measles virus replicates in SLAM+ lymphocytes and dendritic cells, causing immune system damage
Measles virus promotes TH-2 cytokines and reduces TH-1 cytokines

Front 113

How does variola virus evade the IFN immune response?

Back 113

Variola virus produces a soluble vIFNa/b binding protein which serve as decoy receptors, inactivating the IFNs