Session *9 Medical Virology

Front 1

Herpes virus is prevalent in ___

Back 1

eyes

Front 2

Herpes is a large, _____ virus

Back 2

enveloped ds DNA

Front 3

What is the shape of a herpes virus

Back 3

Toroidal (donut shaped?)

Front 4

True or False

Herpes virus is ubiquitous!

Back 4

True - over 120 herpesviruses isolated so far- EVEN YOU could have it.

Front 5

To date, there are 9 known Human Herpesviruses (HHV). List them

Back 5

HSV-1,
HSV-2,
Varicella-zoster (HHV-3),
CMV (HHV-5),
HHV-6A,
HHV-6B,
HHV-7,
Epstein-Barr virus (HHV-4),
HSV-8 (KSHV)

Front 6

True or False- all herpes viruses use the same antigen

Back 6

FALSE- they actually share no common antigen

Front 7

Herpes simplex virus

Back 7

HSV1 and HSV2

Front 8

Varicella-zoster virus

Back 8

(HHV-3, Chicken pox and
shingles

Front 9

Cytomegalovirus

Back 9

HHV-5

Front 10

Kaposi’s sarcoma herpesvirus

Back 10

KSHV or HHV-8)

Front 11

Epstein-Barr virus

Back 11

(HHV-4, Mononucleosis, Burkitt’s
lymphoma

Front 12

_____% of US citizens have HSV1

Back 12

50-70

Front 13

Three subfamilies of Herpes?

Back 13

Write it out

Front 14

The three subfamilies of herpesvirus are based on what 3 biological properties.

Back 14

1. host range
2. length of replication cycle
3. establishment of latency

Front 15

The three subfamilies of herpesvirus are based on what 3 biological properties.

Back 15

1. host range
2. length of replication cycle
3. establishment of latency

Front 16

Alpha herpes

Back 16

Write it out

Front 17

Beta herpes virus

Back 17

Beta has a medium host range

Front 18

Gamma herpes virus

Back 18

Gamma has a very specific host range

Front 19

Alphaherpes are ___ herpes

Back 19

human

Front 20

Characteristics of herpes simplex 1,2

Back 20

•Coldsores, lesions at site of infection, reactivation.
• Rare but often fatal encephalitis
• Keratitis

Front 21

Characteristics of HHV-3 (varicella zoster)

Back 21

• Transmitted by droplets, replicates initially in the nasopharynx
• Latency is established in dorsal root ganglia
• Highly contagious; ~ 95% of adults show serologic evidence of infection

Front 22

HHV-5, Cytomegalovirus are part of which subfamily?

Back 22

Betaherpesvirus

Front 23

Characteristics of HHV-5 Cytomegalovirs

Back 23

1) Congenital: hepatosplenomegaly,
retinitis, rash, and CNS involvement.
2) ~10 % of older children and adults: mononucleosis syndrome with fever,
malaise, atypical lymphocytosis, and
pharyngitis.
3) Immunocompromised hosts: lifethreatening
disseminated disease involving
the lungs, gastrointestinal tract, liver, retina,
and central nervous system.

Front 24

____ is among the most prevalent viral infections worldwide

Back 24

HHV-5 or cytomegalovirus

Front 25

Where does HHV-5 replicate mainly? Where does it shed?

Back 25

In the salivary glands and kidneys.

Shedding occurs in the urine and saliva

Front 26

This virus induces characteristic giant cells with intranuclear inclusions

Back 26

HHV-5 or cytomegalovirus

Front 27

HHV-6,7- is trophic to _____

Back 27

CD 4+ cells

Front 28

True or False
HHV-6,7 is present in nearly everyone by 5 years of age

Back 28

True- think roseola

Front 29

Gamma herpes virus include:

Back 29

HHV-4 (Eppstein barr virus), and HHV-8 (kaposi's sarcoma)

Front 30

Details about HHV-4, Epstein-Barr Virus

Back 30

•Transmitted by intimate contact, particularly via the
exchange of saliva
•Replicates in epithelial cells of the oropharynx and in B lymphocytes
•Widespread in all human populations; causes
infectious mononucleosis
•Establishes latent growth-transforming infection of
B lymphocytes (normally controlled by immune
response).
•Post-transplant lymphoma, Burkitt’s lymphoma,
Hodgkin’s lymphoma, nasopharyngeal carcinoma

Front 31

Details about HHV-8 Kaposi's sarcoma

Back 31

•Isolated in 1994; new model virus that shows how viruses can cause
tumors
•Widespread in sub-Saharan Africa; low levels of infection occur in
most Northern European/North American populations
•Gay/bi-sexual men are more susceptible to infection: AIDS-associated

Front 32

True or False
Herpesviruses establish
acute and latent infections

Back 32

True

Think chicken pox and shingles
Think - cold sore breakouts (yuck)

Front 33

Patterns of Infection for herpes virus

Back 33

1.Acute infection
2. Virus production
3. symptoms
4. viral clearance
5. persistent infection
6. Virus production over
lifetime

Front 34

What is the key to viral latency?

Back 34

Immune system evasion and modulation

Front 35

List some examples of immune system evasion/modulation

Back 35

1. Remain non cytopathic
2. Infect tissues with reduce immune surveillance (such as eye, brain, skin, etc)
3. Directly affect immune system
4.Genome integration/episomal persistence.
5. Produce soluble cytokine decoy-receptors.
6. Block antigen presentation by MHC-I.

Front 36

Draw the 4 components of HSV

Back 36

1. linear ds DNA
2. Icosahedral capsid
3. Tegument with proteins and mRNA
4. Envelopes with 8 proteins and spike glycoproteins

Front 37

HSV-1: capsid is T=

Back 37

16
960 copies of VP5 make up the capsid.

Front 38

HSV 1,2 - Tissue Tropism

Back 38

Viral replication at the site
of entry (mucosal surfaces)Acute/Lytic infection.
-Innate defenses limit viral
spread.
-Progeny virus infects local
sensory neurons.
-Establish latent infection.

Front 39

HSV-1 axonal is transported by _______.

Back 39

the dynein support sytem of microtubules

Front 40

Replication time of HSV is approximately ___ hours

Back 40

8

Front 41

Describe HSV-1 infection cycle

Back 41

1. Virus particle binds to receptors on plasma membrane. Uncoating occurs & DNA enters nucleus.
2.Virion components (±-TIF; VP16)activate immediate early (IE) gene expression.
3. Early (E) gene expression.
4. Viral DNA replication
5. Late (L) gene expression & virus assembly; cell:cell spread.
6. Apoptosis

Front 42

True or False

HSV-1 uses its own RNA polymerase

Back 42

False it uses host RNA polymerase

Front 43

What does immediate early transcript synthesize?

Back 43

alpha proteins wheich are used to trigger the synthesis of early gene expression

Front 44

Beta proteins in HSV-1 of what?

Back 44

They provide DNA replication machinery and can trigger DNA replication

Front 45

What is the role of HSP in HSV-1?

Back 45

It tries to degrade host mRNA and stop translation

Front 46

HSV-1 has greater than how many membrane proteins?

Back 46

10

Front 47

In HSV-1 gc receptor binds to:

Back 47

- gC binds heparin sulfate proteoglycans

Front 48

In HSV-1 gD receptor binds to

Back 48

TNF/NGF related receptors, then undergoes conformational change allowing gB, gH, gI, gL to mediate membrane fusion

Front 49

In HSV-1 entry and uncoating what goes through the nuclear pore?

Back 49

DNA core and ±-TIF, here Genome immediately circularizes upon entry
into nucleus

Front 50

True or False
HSV-1 entry is achieved by receptor mediated endocytosis

Back 50

False- it is by the direct fusion with the PM

Front 51

HSV gC interacts with _____________.

Back 51

cellular heparin sulfate. (HSV-1)

Front 52

gH/gL & gB mediate _____

Back 52

virion penetration.(HSV-1)

Front 53

Describe the HSV-1 genome

Back 53

have ul and us regions flanked by indirect repeats (IR) or direct repeats (dr)

The IR's and multiple ORI allow for different rearrangements

4 ISOMERS!

Front 54

There are ___ isoforms of HSV-1

Back 54

4

Front 55

Draw the 4 isoforms of HSV-1

Are they all infectious?

Back 55

Yes

Front 56

What are the six important regions of the HSV genome?

Back 56

1. linear molecule "a" sequences (circulization and packaging of viral DNA)
2. 9000 long bp repeat (b sequences) that encode a0 (early regulatory protein) and most of the gene for latency associated transcript (LAT)
3. Long unique region (108,000 bp) -replication enzymes and capsid proteins
4. The 6,600 bp short
repeats (RS-C sequences) encodes ICP4
5. The origins of replication.
6. The 13,000 bp unique
short region (US) encodes
12 ORFs for glycoproteins (host range and response for host defense)

Front 57

Function of ICP4?

Back 57

a powerful transcriptional
activator that stimulates all
early viral gene expression
that leads to viral DNA
replication.

Front 58

HSV-1
Ends of linear dsDNA (a
sequences) are important
for

Back 58

packaging

Front 59

HSV-1
Long repeat (b sequences)

Back 59

encoding IE α0 & LATs.

Front 60

HSV-1
Long unique region (UL)–

Back 60

encodes DNA replication and capsid proteins.

Front 61

HSV-1
Short repeats (c sequences)

Back 61

encoding α4 transcription
activator

Front 62

HSV-1
Replication origins

Back 62

OriS and OriL

Front 63

HSV-1
Unique short region (US)

Back 63

encoding host range &
response to host defense
proteins.

Front 64

How many origins of replication does HSV-1 have?

Back 64

3 OriS, OriL, and one other (?)

Front 65

In HSV-1 who makes the transcripts?

Back 65

host pol II

Front 66

True or False
In HSV-1 Protein products of each class regulate expression of proteins in other classes.

Back 66

True

(IE->E->L)

Front 67

In HSV-1 _____enters nucleus enhancing IE viral gene transcription
while_____ specific RNase, attacks host transcripts in cytoplasm

Back 67

Tegument protein ±-TIF (VP16)
vhS

Front 68

In HSV-1 IE mRNAs spliced & exported to cytoplasm to ____

Back 68

make proteins which have regulatory functions.

Front 69

In HSV-1 •α 0 and α 4 stimulate and α 47 inhibits ___.

Back 69

early mRNA synthesis
MHC1 Ag presentation

Front 70

Function of α TIF/VP16) in HSV-1

Back 70

found in the tegument, it acts immediately upon virus
entry to stimulate transcription.

Binding of Hcf (host cell factor) induces conformational
change in α TIF, allowing it to bind Oct-1. Oct-1 binds GAXAT, a component of immediate early gene
promoters for HSV, and thereby enhances transcription.

Front 71

Binding of Hcf (host cell factor) induces conformational
change in α TIF, allowing it to bind Oct-1. Oct-1 binds GAXAT, a component of immediate early gene
promoters for HSV, and thereby enhances transcription.

Back 71

Just review the slide

Front 72

What does vhS protein stand for?

What virus releases it?

Back 72

Viral host shut down protein

HSV-1

Front 73

HcF stands fore what and is found in conjunction with which protein?

Back 73

Host cell factor, VP16
-may have viral latency functions

Front 74

What is OCT-1 and what does it bind to?

Back 74

In HSV-1 Oct-1 binds to garat octomer then to VP16 and HcF complex and is used to enhance early transcription (controls immediate early viral gene expression)

Front 75

What is GARAT and where is it found?

Back 75

It is early gene promotors for HSV

Front 76

As a monomer, VP16 can stimulate transcription at sites

Back 76

distal from the promoter.

Front 77

As a heterotrimer, VP16 stimulates transcription

Back 77

adjacent to viral promoter.

Front 78

Early genes (β) reach peak expression ~____ post infection

Back 78

5-7 hr

Front 79

Functions of (β) coded genes in HSV-1

Back 79

modulating host cellular activities,promoting DNA replication, viral nucleic acid metabolism, DNA repair.

Front 80

Appearance of (β) proteins in HSV-1 signals onset of

Back 80

viral dna replication

Front 81

Early mRNAs are rarely spliced when exported from the nucleus to
generate (β) -proteins. Exported w/ help of

Back 81

ICP-27.

Front 82

β-proteins shut down:

Back 82

IE mRNA synthesis, host protein synthesis and
stimulate late mRNA synthesis

Front 83

HSV-1 has what kind of replication?

Back 83

Rolling Circle

Front 84

7 proteins necessary for HSV-1 replication?

Back 84

DNA polymerase (UL30)
DNA binding proteins(UL42 and ICP8)
ORI binding protein (UL9)and the helicase/primase complex (UL5, 8, and 52).

Front 85

HSV: Rolling circle DNA replication in the nucleus

Back 85

1. 3'OH nicked in dsDNA at an ORI
2. Intact strand copied, displacing 5’ end of nicked strand.
3.Nicked strand copied by
discontinuous DNA synthesis
using RNA primers
4. Multiple cycles of copying intact
circular template &
discontinuous DNA synthesis
generates concatamers.

Front 86

Define concatamer

Back 86

A DNA segment made up of repeated sequences linked end to end.

Front 87

Late ___ genes transcribed off of concatemeric
replicated DNA.

Back 87

γ

Front 88

Functions of γ proteins

Back 88

largely structural and imported into the nucleus or inserted into cellular
membranes

γ proteins also shut down early mRNA synthesis.

Front 89

True or False
in HSV-1 virus DNA replication/L gene expression occurs in discrete
“replication compartments” in the nucleus.

Back 89

True

Front 90

HSV-1 capsid assembly takes place where?

Back 90

In the nucleus via a sequential assembly

Front 91

Draw the HSV-1 capsid assembly

Back 91

30 HSV-1 gene products
are structural components
of the virion.

Front 92

HSV-1: DNA Packaging

Back 92

Empty capsids recognize “a”
packaging sequences of genomic
DNA.
¸ DNA is reeled into capsid until a
headful threshold is reached (1
genome equivalent).
¸ When an “a”-sequence of identical
orientation to the first is encountered,
the genome is cleaved in direct
repeat 1 (DR1) region.
¸ The genome may be replicated
within 20 minutes, a feat that
requires 15,000 nucleotides/
min/strand to be polymerized.

Front 93

HSV-1
_____ directs budding of
through inner nuclear
membrane via ______.

Back 93

gpUL31
gpUL34

Front 94

True or False

During budding of HSV-1 the virus loses its outer envelope

Back 94

True

HSV-1 acquires and looses membranes during assembly (enveloped, de-enveloped, enveloped and so on)

Front 95

Complete cycle of HSV-1 (no details)

Back 95

Immediate Early
Early
Late
Acute infection cycle
Lytic infection

Front 96

______: viral RNAs
generated during latent infection (40-100,000/neuron).

Back 96

Latency associated transcripts

Front 97

LAT's in HSV-1 lack what and are found where?

Back 97

lack polyA tails; restricted to nucleus.

Front 98

LATS may bind ____ to prevent its transcription &
subsequent transactivation of early genes.

Back 98

ICP0

Front 99

Typical HSV-1 clinical manifestations can occur because

Back 99

sun burn, stress, nerve damage, menstruation, steroids,

Front 100

HSV-1: Immune system evasion

Back 100

-HSV shuts off host cell protein synthesis
-HSV can make inactive cytokine homologs that bind
cytokine receptors "decoys"
-HSV blocks apoptosis

Front 101

Herpesvirus ICP47 inhibits

Back 101

TAP translocator,

Front 102

HSV: Reactivation is

Back 102

acute

Front 103

MHC-2 presentation for HSV-1
___activates antiviral response and clears infection

Back 103

(DC and M)

Front 104

HSV-1: Histopathology

Back 104

Virus-mediated cell death
≤ Nuclear degeneration.
≤ Multi-nucleated cells
≤ Vesicular fluid between
epidermis and dermal layer.
≤ Intense inflammatory response
in dermal layer
≤ Healing results in pustules.

Front 105

HSV-1 accounts for 95% of _____ in US.

Back 105

viral encephalitis

Front 106

HSV-1 and yer eyes

Back 106

Herpetic keratitis AND Corneal ulcer with hypopyon (collection of pus in the anterior chamber of the eye).

Front 107

Acyclovir treats what and how does it work?

Back 107

HSV-1

nucleoside chain terminator
ACV phosphorylated
1st by viral thymidine
kinase (TK) and then
by cellular kinase to
produce ACV triphosphate
which competes with dGTP
for DNA polymerase

Front 108

____ of all Americans are infected with HSV-1

Back 108

50-80%

Front 109

True or False

Most people who transmit HSV-1 are asymptomatic.

Back 109

True

Front 110

True or False

Co-infection with HSV-1 and HSV-2 is common

Back 110

True

Front 111

Chicken pox

Back 111

(Varicella)
10 replication at site of infection
followed by spread through blood
stream (viremia).
Complications are rare.

Front 112

Shingles

Back 112

(Zoster)
After primary infection, virus
persists in sensory ganglia of CNS

Front 113

Varicella-Zoster Virus (VZV) QUICKIES

Back 113

Enveloped icosahedral
capsids.
• Linear dsDNA– 112 kb in
size with 68 ORFs.
• Molecular biology similar to
HSV in many respects…

Front 114

IN VZV every bump =

Back 114

1 infected T-cell
(that eventually undergoes
apoptosis

Front 115

Pathogenesis of VZV

Back 115

respiratory/contact
transmission
-systemic infection
-Tonsil T-cells - motility
-virus delivered to skin through cappillaries

Front 116

True or False
VZV and HSV can be distinguished from one another by classical histological staining such as hematoxylin & eosin.

Back 116

False- it cannot

Front 117

Varicella most common in ___, but zoster is common ___

Back 117

winter/spring
all year long

Front 118

VZV: Therapeutics

Back 118

Acyclovir/Ganciclovir
Foscarnet
Vidarabine
VZIG

Front 119

Acyclovir/Ganciclovir

Back 119

Most effective drug against VZV. Reduces duration of
disease, pain and viral shedding.

Front 120

Foscarnet

Back 120

Used for acyclovir-resistant strains of VZV.

Front 121

Vidarabine

Back 121

Inhibits nucleic acid synthesis. (VZV)

Front 122

VZIG

Back 122

Varicell-zoster immunoglobulin can prevent or reduce
symptoms. Protection lasts ~ 3 weeks. This passive
immunnization is recommended for immunocompromised
individuals, pregnant women, newborns and hospital
personnel who have been exposed to the virus.

Front 123

VZV Vaccine: ______% EFFECTIVE

Back 123

85

Front 124

VZV Differences from HSV:

Back 124

-Respiratory secretions are infectious
-Systemic disease
-The rash itches
-Virus is latent in multiple sensory ganglia

Front 125

Cytomegalovirus (CMV/HHV5) QUICKEE

Back 125

Betaherpesvirinae
≤ One serotype
≤ Structure similar to
HSV (envelope,
tegument, capsid)
≤ Linear dsDNA
genome (230-240 kb
in size)… the
largest!

Front 126

CMV: Transmission by

Back 126

Age Group

Fetus ----- Across placenta
Infant ----- Contact with maternal body fluids
during birth; breast-feeding
Youth ----- Contact with urine/saliva from
other children
Adults ----- Kissing; sexual intercourse; blood
transfusion

Front 127

True or False
CMV goes away eventually

Back 127

False - though it is silent, it lasts a lifetime.. however no destruction of human cells

Front 128

CMV latent persistance in ____ and_____

Back 128

monocytes and neutrophils

Front 129

Immune response ____ against primary infection of CMV,
but not against reactivations.

Back 129

(IgM and IgG)

Front 130

True or False

Most people are infected with CMV worldwide

Back 130

TRUE

Front 131

Symptoms of CMV (HHV5)

Back 131

prolonged high fever, chills, severe fatigue

Front 132

CMV diagnosis with....

Back 132

Test for IgM or IgG using ELISA.

PCR (the ‘gold-standard’).

Front 133

Treat CMV with...?

Back 133

Treated with Ganciclovir
(Acyclovir is not effective
because CMV does not have
thymidine kinase).

Front 134

Does CMV have a vaccine?

Back 134

No

Front 135

____ is the most common virus transmitted to a pregnant
woman's unborn child

Back 135

CMV

Front 136

Congenital CMV (meaning present at birth) is as common a cause of serious disability such as:

Back 136

Down syndrome, fetal alcohol
syndrome, and neural tube defects

Front 137

CMV: Histopathology

Back 137

Cytoplasmic Inclusions
CMV nuclear inclusions with perinuclear halo
reactive alveolar lining cells

Front 138

_____ blocks antigen presentatio nby MHC-1 in HSV-1

Back 138

ICP47

Front 139

Is there a treatment for CMV

Back 139

No

Front 140

HHV6 and HHV7 are what kind of herpesvirus?

Back 140

Beta

Front 141

HHV6/7 Tropism

Back 141

CD4+ T- cells predominant
targets– CD4 is not the
receptor).
• B- cells & macrophages
can be infected
• Enlargement of
lymphocytes followed by
lytic degeneration.

Front 142

What are the two variants for HHV6/HBLV (human B-lymphotropic virus?

Back 142

HHV6-A and HHV6-B

Front 143

HHV6 in children cause what?

Back 143

"roseola infantum", a common childhood rash

Front 144

HHV6: Transmission & clinical manifestations

Back 144

Virus present in saliva- may spread by
fomites and aerosol.
CNS infection - encephalitis
Skin infection - rash
Liver infection - liver dysfunction

Front 145

HHV6 Latency and
reactivation (draw it)

Back 145

Ugh

Front 146

HHV6 Latency and
reactivation (draw it)

Back 146

Ugh

Front 147

Human herpesvirus 7 (HHV-7)quickee

Back 147

•betaherpesvirus
• First isolated from human CD4+ cells in 1990.
• Genome ~170 kbp, organization similar to HHV-6.
• The complete genome sequence of HHV-7
determined; shows a high degree of conservation
with HHV-6.
• However, only limited antigenic cross-reactivity
between the two viruses.
• At present, there is no clear evidence for the
direct involvement of HHV-7 in any human disease.

Front 148

List two Gammaherrpessvviirrussess

Back 148

EBV (HHV-4) and Kaposi's Sarcoma (HHV8)

Front 149

EBV caused by ___ and causes ___.

Back 149

•Transmitted by intimate contact, particularly via the
exchange of saliva

infectious mononucleosis

ALSO-•Post-transplant lymphoma, Burkitt’s lymphoma,
Hodgkin’s lymphoma, nasopharyngeal carcinoma

Front 150

HHV8: Kaposi’s sarcoma herpesvirus QUICKEE

Back 150

Structural genes similar
to other HV.
≤ Genome has numerous
homologs to mammalian
regulatory genes (incl.
VEGF) in an “oncogene
cluster”.
o Molecular piracy.

Front 151

How many serotypes does HBV have?

Back 151

Two

Front 152

This HV is ...
• Associated with tumors:
✔ Burkitt’s lymphoma
✔ Nasopharyngeal carcinoma

Back 152

EBV

Front 153

EBV Infects and establishes
latency in _____.

Back 153

B-cells

Front 154

True or False
EBV is Often asymptomatic children

Back 154

True

Front 155

EBV: Pathology/Clinical Manifestations

Back 155

Barfing, tonsillar exudate, skin rash, fever, accumulation of atypical lymphocytes

Front 156

Burkitt’s Lymphoma Quickee

Back 156

Proliferative B-cell
disease.
• Rate of cell division
among highest in
human tumors.
• C-Myc mutation linked
to Burkitt’s Lymphoma.
• Role of EBV still
under study.

Front 157

“The Commonest Children’s
Cancer in Tropical Africa”

Back 157

Burkett's Lymphoma

Front 158

True or False

Shingles may provide chronic
stimulus of B-cells that
carry latent EBV.

Back 158

False- It's Malaria that is the constant stimulus

Front 159

EBV: Genomic Structure Quickee

Back 159

dsDNA; 172 kb
• Long & short repeat
regions
differentiate EBV-1
from EBV-2.
• Replication occurs
in the nucleus

Front 160

Infection Cycle in B-cells

Back 160

Mimics normal
B-cell differentiation
• Virus appears to drive B-cell differentiation into “long-lived memory cells”

Front 161

Why cause differentiation
into memory cells? (Burkitts lymphoma)

Back 161

EBV not recognized by immune system

Front 162

Role of EBNA-1 (Epstein-Barr
nuclear antigen) in replication?

Back 162

EBNA-1 piggybacks on host cell chromosomes,mediating viral replication

Front 163

What does EBV have to do with cancer?

Back 163

Burkitt’s Lymphoma cells have a “germinal centre”
phenotype
- microscopically distinguishable regions of lymphoid tissue where B
cells expand and undergo selection
• It is thought that c-myc (host cell cycle regulation protein)
translocation occurs during somatic
hypermutation
- process during B cell differentiation to mutate variable regions
of immunoglobulin genes to recognize foreign elements

EBV is a virus that infects B lymphocytes, causing them to grow and divide and extending their lifespan. In most people, it causes infectious mononucleosis, also known as "mono." Mono is usually not a serious disease because the patient’s T cells destroy B cells infected with EBV. But when people have a T-cell deficiency (which may be present at birth, secondary to HIV infection, or caused by drugs that decrease their function such as after a transplant), the EBV-infected B cells grow and accumulate. These growing cells have an increased risk for developing DNA mutations or gene translocations. If these changes affect certain oncogenes or tumor suppressor genes, lymphoma will develop.

Front 164

_____is a process during B-cell differentiation, during
which mutations are actually part of the process

Back 164

somatic hypermutation

Front 165

Role of C-Myc (host cell cycle regulation protein)

Back 165

• Oncogene
• Normal cell C-Myc gene
functions in regulation of:
- Cell cycle and growth
• Mutation of C-Myc causes “gain
of function” phenotype
• BUT- rarely (if ever) is cancer
associated with just one
mutated gene

Front 166

EBV Host Cell Entry - whats the receptor?

Back 166

Main receptor is viral gp350, binding to CD21
- MHC Class II co-factor
- Important co-receptor is gp42, thought to
mediate membrane fusion
Much less know about entry in epithelial cells.

Front 167

EBV Genome & Replication qUICKEE

Back 167

dsDNA linear genome in virion
- DNA circularizes upon entry into
nucleus
-172 kb, encodes over 100 viral proteins
-Replication occurs in the nucleus,
associated with viral replication
compartments
-which may block host cell DNA
replication
-Compartments dissociate when vDNA is
packed into nucleocapsid in nucleus
- Virion packaged in cytoplasmic vesicles

Front 168

Protein of EBV

Back 168

UGH

Front 169

EBV can transform resting B-cell to Post-Immortal B-cell in vitro

How?

Back 169

Resting B-cell
Pre-Immortal B-cell
Post-Immortal B-cell
Tumorigenic Cell

Strong Telomerase Upregulation
Activity Critical
-Telomeres cap chromosomes, and serve to regulate how many times a cell can replicate
- Telomerase maintains/ increases telomere length

* c-Myc translocation
causes this too!

Front 170

Role of EBNA-1

Back 170

Burkitt’s Lymphoma tissue only expresses
one viral protein: EBNA-1
- EBNA-1 is also the only protein expressed in dividing memory B-cells
- Expressed in all EBV-related
malignancies
• EBNA-1 is critical to transcription and
replication of the virus
- it’s also critical to regulating the push from naïve infected B-cell to long-lived memory cell