Test 1 - Effects of Viruses on Host Cell (9)

Question 1

What are the three mai effects that a virus can have on the host cell?

Answer 1

1. Cytocidal (leads to death)
2. Non-cytocidal (persistent infection)
3. Cell transformation (Tumor cells)

Question 2

What is the cytopathic effect?

Answer 2

Refers to damage or morphological changes to host cells during virus invasion.

Primary: induced by viral replication and viral proteins toxic to host

Secondary: effects of metabolic needs of the virus

Question 3

Describe the changes seen in the following cytopathic effects.

1. Complete destruction of cells
2. Subtotal destruction of cells
3. Focal destruction of cells

Answer 3

1. Most severe. All cells in the monlayer rapidly shrink become dense (pyknosis) and detach from the glass within 72 hours.
2. Consists of detachment (death) of some but not all of the cell sin the monolayer.
3. Produce localized areas of infection

Question 4

Define pyknosis.

What kind of cytopathic effect is this associated with?

Answer 4

A degenerative condition of a cell nucleus marked by clumping of the chromosomes, hyperchromatism, and shrinking of the nucleus.

Question 5

What are visible effects of virus induced cell damage?

Answer 5

• Cell lysis
• Cell rounding
• Cell detachment
• Vacuoles in cytoplasm
• Inclusion bodies
• Syncytium formation
• Antigenic changes in cell membrane
• Swelling and Clumping

Question 6

Describe the process of cell fusion.

Answer 6

AKA Syncytium or polykaryon formation

• Involves the fusion of the plasma membranes of four or more cells to produce an enlarged cell with four or more nuclei. Prone to premature Cell Death.
• Result from the fusion of an infected cell with neighboring infected or uninfected cells.
• Enveloped viruses specifically direct the insertion of their surface glycoproteins, including fusion proteins, into host‐cell membranes as part of their budding process, often leading to membrane fusion and syncytium formation.
• Syncytia formation may be the only detectable CPE of some paramyxoviruses.

Question 7

What are inclusion bodies?

Answer 7

• An abnormal structure in a cell nucleus or cytoplasm or both, such as aggregates of proteins, having characteristic staining properties and associated with certain viral infections.
• Help to identify certain viral infection.

Question 8

What can inclusion bodies be made of?

Answer 8

• Accumulation of viral components, such as Negri bodies consist of ribonuclear proteins produced by the rabies virus.
• Result from degenerative changes in cell, such as Owl’s eye inclusion bodies seen in herpesvirus infection
• Crystalline aggregates of virions, such as in adenovirus infection.

Question 9

TRUE/FALSE.

Inclusion bodies are usually type of protein and therefore, stain basophilic.

Answer 9

FALSE.

They can be either basophilic or acidophilic.

Question 10

What are some general mechanisms of virus-induced cell injury and death?

Answer 10

• Inhibition of Host-cell nucleic acid synthesis
• Inhibition of Host-cell RNA Transcription (mRNA production and processing)
• Inhibition of Host-cell protein synthesis
• Release of lysosomal hydrolytic enzymes
• Interference with cellular membrane function (e.g. formation of syncytium)

Question 11

In relation to the viral life cycle, how do lysis and apoptosis differ?

Answer 11

During lysis, viral replication is complete and progeny virions are released. However

Question 12

What are the two apoptotic pathways?

Answer 12

• Mitochondrial (intrinsic)
• Death receptor (extrinsic)

Question 13

Describe the mitochondrial pathway.

Answer 13

The mitochondrial pathway is activated as a result of increased permeability of mitochondrial membranes subsequent to cell injury, such as that associated with a viral infection.

Question 14

Describe the death receptor pathway.

Answer 14

The extrinsic pathway is activated by engagement of specific cell‐membrane receptors, which are members of the TNF receptor family (TNF, Fas, and others). Thus binding of the cytokine TNF to its cellular receptor can trigger apoptosis.

Similarly, cytotoxic T lymphocytes that recognize virus‐infected cells in an antigen‐specific manner can bind the Fas receptor, activate the death domain, and trigger the executioner caspase pathway that then eliminates the cell before it becomes a functional virus factory.

Question 15

What cells can initiate apoptosis? What enzymes are released?

Answer 15

Cytotoxic T lymphocytes and natural killer cells can also initiate apoptosis of virus‐ infected target cell, utilizing preformed mediators such as perforin and granzyme that directly activate caspases in the target cell.

Question 16

TRUE/FALSE.

Non-cytocidal viruses typically produce persistent infections which produce and release virions. Many times, the cells may still grow and divide.

Answer 16

TRUE.

Question 17

How do non-cytocidal changes in virus affect somatic cells and terminally differentiated cells differently?

Answer 17

With few exceptions (e.g., some retroviruses), these slow progressive changes ultimately may lead to cell death.

• However, in the host animal, cell replacement occurs so rapidly in most organs and tissues that the slow fallout of cells as a result of persistent infection may have no effect on overall function.
• But, terminally differentiated cells such as neurons (Nerve Cells), once destroyed, are not replaced, and persistently infected differentiated cells may lose their capacity to carry out specialized functions.

Question 18

Define cell transformation.

Answer 18

the changing of a normal cell into a cancer cell

Question 19

Define neoplasia.

Answer 19

a descriptive term that denotes an abnormal tissue overgrowth that may be either localized or disseminated. It is the process that leads to the formation of neoplasms (syn. carcinogenesis).

Question 20

Define oncology.

Answer 20

study of neoplasia and neoplasms

Question 21

A _______ is a growth produced by abnormal cell proliferation that remains

localized and does not invade adjacent tissue.

Answer 21

benign neoplasm

Question 22

A _______ is locally invasive and may also be spread to other parts of the body (metastasis).

Answer 22

malignant neoplasm (syn. cancer)

Question 23

Define oncogenic viruses.

Answer 23

Viruses that cause or give rise to tumors.

Question 24

TRUE/FALSE.

Neoplasms (tumors) arise as a consequence of the dysregulated growth of cells derived from a population of genetically altered progenitor cells.

Answer 24

FALSE.

It only takes one

Question 25

How does metastasis occur?

Answer 25

Metastasis is the spread of cancer cells from the part of the body where it started (the primary site) to other parts of the body. When cancer cells break away from a tumor, they can travel to other areas of the body through the bloodstream or the lymph system, and develop secondary tumors in other parts of body.

Question 26

___________ encode proteins that function in normal cellular growth and differentiation, while _______ encodes proteins that regulates and inhibits uncontrolled growth (keeps cell division in check)

Answer 26

Proto-oncogenes

Tumor suppressor genes

Question 27

What are proto-oncogenes involved in?

What do they encode?

Answer 27

Growth signaling and anti-apoptotic pathways.

Growth factor proteins, growth factor receptors, transcription factors, intracellular signaling proteins, signal transducers.

Question 28

Mutated forms of proto-oncogenes or aberrantly expressed proto-oncogenes are known as ________.

Why are they cause problems?

Answer 28

Oncogenes

Why:

• These onco-proteins function in an unregulated manner, i.e. do not respond to regulatory signals.
• Synthesis of aberrant growth factors, growth factor receptors, etc. that trigger uncontrolled proliferation of cells.
• Defective differentiation of cells.
• Failure to undergo apoptosis.

Question 29

What kind of proteins do tumor suppressor genes encode? What are their functions?

Answer 29

Encode proteins that inhibit cell proliferation (by holding cell cycle at G1 phase).

Functions:

• Inhibits the expression of genes that are essential for the continuing of the cell cycle.
• Connecting the cell cycle to DNA damage, i.e. if cell has damaged DNA it will not divide.
• Repair of damaged DNA
• If repair effort fails, apoptosis of cells
• Adhesion proteins known as metastasis suppressors that prevent spread of cancer
• cells, or metastasis.

Question 30

What are some tumor suppressor proteins?

Answer 30

Retinoblastoma protein

p53 protein

Question 31

What kind of genome do oncogenic viruses normally have?

Answer 31

DNA

Retroviruses are the most important

Question 32

TRUE/FALSE.

DNA oncogenes are an essential part of the viral genome, encoding proteins which alter patterns of gene expression and regulation of cell growth (induce transformation).

Answer 32

TRUE

In every case the relevant genes encode early proteins having a dual role in virus replication and cell transformation.

Question 33

What are the two ways that oncogenic DNA viruses interact with cells?

Answer 33

(1) productive infection in Permissive cell, in which the virus completes its replication cycle, resulting in cell lysis, or
(2) non-productive infection in Nonpermissive cell, in which the virus transforms the cell without completing its replication cycle. During such non-productive infection, the viral genome or a truncated version of it is integrated into the cellular DNA; alternatively, the complete genome persists as an autonomously replicating plasmid (episome).

Question 34

All RNA tumor viruses belong to the family __________.

Answer 34

Retroviridae

Question 35

____________ are host genes that encode important cell signaling products that regulate normal cell proliferation.

Answer 35

c-onc genes/proto-oncogenes

Question 36

How are acute transforming retroviruses directly oncogenic?

Where does this originate from? How does this become oncogenic?

Answer 36

By carrying an additional viral oncogene, v-onc

The retroviral v-onc originates from a host c-onc gene/proto-oncogene which is inserted into the virus genome usually by recombination events between provirus DNA and host DNA, i.e. v-onc genes are c-onc genes separated from host genome and inserted in virus genome.

Viral genome is inserted into the host genome via recombination. However, when it is inserted it lacks regulatory machinery, giving it the ability to divide uncontrollably.

Question 37

Describe a slow/chronic transforming retrovirus.

Answer 37

Virus gene do not contain v-onc gene. The integration of retroviral genes into host chromosomal DNA can occur at promoter or enhancer sites that drive the increase in proto- oncogene/c-onc gene expression, leading to malignant transformation of the cell.

Question 38

Define promoter and enhancer genes.

Answer 38

Promoter: DNA sequence at which DNA-dep RNA polymerase binds to initiate transcription

Enhancer: A transcriptional regulatory sequence located some distance from the promoter; it increases the rate of initiation of transcription

Question 39

What are the characteristics of transformed (neoplastic) cells?

Answer 39

• Changes in morphology (more spindle-shaped)
• Loss of contact inhibition
• Expression of tumor antigens

Question 40

What are tumor antigens?

Answer 40

New antigens appear on the surface of tumor cells that may provoke an immune response. These are abnormal proteins that arise from mutations and are broadly classified into.

• Products of Mutated Oncogenes and Tumor Suppressor Genes (Tumor-Specific antigens)
• Products of Other Mutated Genes (Tumor-associated antigens)

The immune system recognizes these abnormal antigens as foreign and tries to destroy the tumor cells. However, these abnormal molecules often are not appropriately presented to cells of immune system, such as cytotoxic T cells.

Question 41

What are the 5 classes of tumor antigens?

Answer 41

• Differentiation antigens
• Mutated proteins
• viral coded proteins
• Cancer/testis antigens
• Excessive amounts of normal proteins