Molecular Biology And Human Herpes 1

Question 1

How are herpesviruses transmitted?

Answer 1

Via intimate contact with body fluids

Question 2

What is the herpes virus structure?

Answer 2

Linear ds DNA genome

Question 3

What are alpha herpesviruses?

Answer 3

Herpes simplex virus types 1 and 2, and varicella-zoster virus

Question 4

What are characteristics of alpha herpesviruses?

Answer 4

Short replicative cycle, broad host range, characteristically establish latent infection in sensory nerve ganglia

Question 5

What are beta herpes viruses?

Answer 5

Cytomegalovirus, human herpesviruses 6 and 7

Question 6

What are characteristics of beta herpesviruses?

Answer 6

Long replicative cycle, restricted host range
Establish latent infection in secretory glands or reticuloendothelial system and the kidneys

Question 7

What are gamma herpesviruses?

Answer 7

Epstein-Barr virus and human herpes viruses 8

Question 8

What are characteristics of gamma herpes viruses?

Answer 8

Very restricted host range
Latent infection in lymhoid cells
Lytic infection in specific epithelial

Question 9

What is the HSV1 genome?

Answer 9

Segmented linear genome, unique long and short covalently attached molecules

Question 10

How many different genome rearrangements can HSV-1 genome have?

Answer 10

Both segments (long and short) can be inverted, resulting in 4 different genome rearrangement possibilities
(P, IL, IS, or ILS)

Question 11

How many different glycoproteins of HSV-1 are there?

Answer 11

12
(B, C, D, E, G, H, I, J, K, L, M and N)

Question 12

What is overview of HSV-1 life cycle entry?

Answer 12

Virus particles encounters a cell, glycans on surface allow lots of things to weakly assocaited, low affinity reactions before virus bumps into primary receptor and initiates high affinity
Then get fusion and glycoprotein D undergoes structural change to induce membrane fusion then release of capsid into cytoplasm

Question 13

What happens in HSV-1 following fusion?

Answer 13

Capsid is released to cytoplasm with some attached tegument proteins
VP16 separates and translocates to the nucleus
Capsid travels to the cell nucleus using microtubukes
Linear DNA enters the nucleus

Question 14

What happens in HSV-1 immediate early transcription?

Answer 14

VP16 enters the nucleus with HCF-1 and Oct-1
Transcription of alpha genes
ICP0
ICP4
ICP22
ICP27

Question 15

What does ICP0, 4, 22 and 27 do?

Answer 15

0 - potent transactivator of gene expression
4 - positive regulation of intermediate and late genes
22 - regulates expression of 0
27 - negatively regulates alpha genes and upregualted late genes

Question 16

What happens in HSV-1 early transcription?

Answer 16

Alpha genes participate in transcription of beta genes
Genes work cooperatively to induce transcription of late gamma genes
True-late genes down-regualte beta gamma genes progressively expressed, gene transcription

Question 17

What happens in HSV-1 encapsulation?

Answer 17

Mature, DNa containing capsids exit nucleus
Glycoproteins traverse form ER thorugh Golgi to the cell surface
Capsid acquire elements of tegument en route to exosome machinery
Mature particle buds from exosome

Question 18

What stimulates alpha gene expression?

Answer 18

VP16

Question 19

What is the negative feedback loop of alpha beta and gamma genes?

Answer 19

Alpha genes stimulate beta genes
Alpha and beta genes simulate gamma gene trasncpriton
Gamma genes downregulate beta genes
Gamma and beta genes downregulate alpha genes

Question 20

What is lysis event of HSV-1 induced by?

Answer 20

Caspase 8 activation

Question 21

What cell type does HSV-1 primarily infect?

Answer 21

Epithelial cells
But can invade and replicate in CNS, establishing latent infection in dorsal root ganglia

Question 22

What are the key features of HCMV life cycle?

Answer 22

Oropharyngeal cavity is seeded and lungs become infected
Innate effector recruitment
Imamate immune cell infection
Primary dissemination
Viral replication to high titre
Secondary dissemination
Viral replication in salivary gland, mammary glands, kidneys etc.
HCMV infected bodily secretions

Question 23

What is the prevalence of HCMV in adult populations?

Answer 23

Is roughly 70%

Question 24

How is HCMV transmitted?

Answer 24

Via urine, saliva, blood, tears, semen, breast milk, transplanted organs and blood transfusions

Question 25

How can HCMV enter?

Answer 25

Tries to enter via fibroblast - get pH independent plasma membrane fusion Epithelial cells - similar receptors bit endosome uptake - Endocytosis Myeloid cells - macropinocytosis

Question 26

How does innate immune system detect cytosolic dsDNA?

Answer 26

CGAS detects dsDNA CGAS catalyses synthesis of cGAMP cGAMP activates mediator of IRF3 activation (MITA) MITA activates IRF3 leading to transcription of type 1 IFNs

Question 27

Why is MITA important in HCMV

Answer 27

Important has HCMV will inhibit it , number of proteins act on this pathway to disrupt expression of type 1 interferons

Question 28

What does UL82 do in HCMV?

Answer 28

Inhibitors MITA

Question 29

What does HCMV latently infect?

Answer 29

CD33+/CD34+ cells in the bone marrow and differentiated CD14+ monocytes in the peripheral blood

Question 30

How does HCMV reactivate?

Answer 30

Occurs when HCMV-infected cells enter the tissue, cells differentiate into macrophages or dendritic cells Spread of locally-reactivated HCMV infection is prevented

Question 31

What is reactivation of HCMV mostly assocaited with?

Answer 31

Pneumonitis

Question 32

What is the seroprevalence of EBV?

Answer 32

80-90%

Question 33

Where does EBV replicate?

Answer 33

In epithelial cells of the pro-pharynx

Question 34

Where does EBV establish latent infection?

Answer 34

In dividing populations of B cells

Question 35

How does EBV entry occur?

Answer 35

Not just one mechanism Have clusters of glycoproteins that cna bind different ligands to infected either a B cell (CD21/MHC2) or epithelial cell (integrins)

Question 36

What is primarily involved in initiating fusion of EBV?

Answer 36

GHGL

Question 37

What does primary infection with EBV lead to?

Answer 37

Infectious mononucleosis

Question 38

What does chronic infection of B cells from EBV lead to??

Answer 38

Burkitt’s lymphoma Nasopharyngeal carcinoma Primary effusion lymphoma

Question 39

What type of burkitt’s lymphoma is EBV assocaited with?

Answer 39

Endemic BL

Question 40

What is the likely cellular origin of EBV assocaited burkitt’s lymphoma?

Answer 40

B cells of the germinal centre

Question 41

What is EBV-associated nasopharyngeal carcinoma?

Answer 41

Rare type of cancer affecting the throat connecting the back of the nose to the back of the mouth

Question 42

What does the development of nasopharyngeal carcinoma involve?

Answer 42

Early exposure to environmental factors Early exposure to high risk EBV subtypes Hereditarily genetic predisposition EBV-induced genetic destabilisation in NP cells

Question 43

What is NPC genetic predisposition?

Answer 43

More common in men Increased prevalence in south-eastern Asia and southern china

Question 44

What is PEL?

Answer 44

EBV assocaited primary effusion lymphoma Is a rare B cell lymphoma

Question 45

Where is PEL usually found?

Answer 45

In body cavities

Question 46

What is an effusion?

Answer 46

An abnormal collection of fluid in hollow spaces or between tissues of the body