Module 9

Front 1

Question 1: State 2 living and non-living characteristics of viruses.

Back 1

Living characteristics of viruses:
- The reproduce at a fantastic rate, but only in living host cells.
- They can mutate

Non-living characteristics of viruses:
- Acellular (contain no cytoplasm or cellular organelles).
- No metabolism on their own and must replicate using the host cells metabolic machinery. (ie don’t grow and divide). Instead, new viral components are synthesized and assembled within the infected host cell.
- Possess DNA or RNA but never both.

Front 2

Question 2: Briefly explain why viruses can’t replicate on environmental surfaces or in synthetic laboratory medium.

Back 2

Viruses contain only one type of nucleic acid: DNA or RNA, but not both.
Viral components must assemble into complete viruses (virions) to go from one host cell to another.
Since viruses lack metabolic machinery of their own and are totally dependent on their host cell for replication, they cannot be grown in synthetic culture media.

Front 3

Question 3: List 4 shapes of viruses

Back 3

1) Helical: viruses consist of nucleic acid surrounded by a hollow protein cylinder or capsid and possessing a helical structure (‘naked virus’)
2) Polyhedral: viruses consist of nucleic acid surrounded by a polyherdral (many-sided) shell or capsid, usually in the form of an icosahedrons (‘naked virus’).
3) Enveloped: viruses consist of nucleic acid surrounded by either a helical or holyhedral core and covered by an envelope.
4) Binal: (complex) viruses have neither helical nor polyhedral forms, are pleomorphic (irregular shaped), or have complex structures.

Front 4

Question 4: Briefly describe the structure of most viruses that infect humans and state where the viral envelope is derived from.

Back 4

- A genome: the viral genome is a single or segmented, circular or linear molecule of nucleic acid functioning as the genetic material of the virus. It can be single-stranded or double stranded DNA or RNA, and codes for the synthesis of viral components and viral enzymes for replication.
- A capsid: or core is a protein shell surrounding the genome and is usually composed of protein subunits called capsomeres. The capsid serves to protect and introduce the genome into host cells. Some viruses consist of no more than a genome surrounded by a capsid and are called nucleocapsid or naked viruses. Attachment protein project from the capsid and bind the virus to susceptible host cells.
- An envelope: most animal viruses, also have an envelope surrounding a polyhedral or helical nucleocapsid, in which case they are called enveloped viruses. The envelope is composed of phospholipids and glycoprotein and for most viruses, is derived from host cell membranes by a process called budding.
- The viral envelope is derived from:
i. (If) Enveloped, derived from host cell by budding: viral glycoprotein spikes in envelope bind host cell receptors
ii. The envelope may come from the host cell’s nuclear membrane,

Front 5

Question 5: Name the 6 steps involved in the productive life cycle of enveloped viruses.

Back 5

Attachment or adsorption
– Penetration
– Uncoating
– Replication
– Maturation
– Release
– Reinfection

Front 6

Question 6: When a virus infects the body, the body responds by producing antibodies that coat the virion. Discuss briefly how these antibodies offer protection to the body and state what would happen if a person was unable to produce antibodies to that virus.

Back 6

One of the major defences against free viruses is the production of antibodies (Ab) against the virus. The "tips" of the antibody (the Fab portion) have shapes that have a complementary shape to portions of viral attachment protein and glycoprotein epitopes on the viral surface. When Ab binds the viral epitopes, they block viral adsorption to host cell receptors and, thus, block viral replication. Ab made to virus also opsonise viruses to increase phagocytosis.
In the absence of the antibodies against the infected virus, virus would proliferate at an exponential rate until the host is severely damaged or dead.

Front 7

Question 7: One of the experimental approaches to preventing viral infection is to use recombinant DNA technology to artificially synthesize the host cell receptor molecule to which a specific virus would normally attach and then therapeutically administer this receptor to people prior to viral exposure. Briefly discuss how this might offer protection to the body.

Back 7

For a virus to infect a host cell, that cell must have receptors for the virus on its surface and also be capable of supporting viral replication. The host cells which have artificially synthesised receptors will not have the specific requirements for the virus to reproduce. Hence it prevents the continuity of the life-cycle of the particular virus in the host.

Front 8

Question 8: Comment on why viruses are generally ecotropic. That is, very specific as to the types of hosts, tissues, and cells they are able to infect.

Back 8

Viruses are generally ecotropic because it is evolved to suit specific conditions. Different types of cells of the body are often unique from other cells in relations to its environment, cellular content, enzymes and activity. Therefore, viruses that have been adapted and selected to suit the above factors are allowed to strive.

Front 9

Question 1: Name 4 herpes viruses that may have a latent life cycle, state in what cell types they become latent, and name the diseases each cause.

Back 9

1) Herpes simplex type 1 (HSV-1)
- Which usually causes fever blisters or oral herpes
HSV-1 tends to reside in the trigeminal ganglia
2) Herpes simplex type 2 (HSV-2)
- Which usually causes genital herpes
HSV-2 tends to reside in the sacral ganglia
3) Epstein- Barr virus (EBV)
- Latency in B-cells
- Which causes infectious mononucleosis and plays a role in certain cancers
- Swollen adenoids (glandular fever)
- Cancer in B-cells: Burkitts lymphoma.
- Nasopharyngeal carcinoma, periodontitis, hairy lekoplakia.
4) Varicella – Zoster virus (VZV)
- Which causes chicken pox and shingles
Remains dormant in trigeminal and dorsal root ganglia.
5) Cytomegalovirus (CMV)
- Which causes a variety of infections in immunosupressed persons and is also a leading cause of birth defects.
Remains dormant in Bone marrow (T-cells)

Front 10

Question 2: Define provirus.

Back 10

A provirus is a virus genome that has integrated itself into the DNA of a host cell (wiki)

Front 11

Question 3: Name 4 viruses that have been implicated in human cancers.

Back 11

1) Hepatitis B virus (HBV)
2) Hepatitis C virus (HCV)
3) Human papilloma virus (HPV)
4) Epstein- Barr virus (EBV)
5) Human T-lymphotropic virus type 1 (HTLV-1)

Front 12

Question 4: Briefly describe at least 6 ways viruses can damage infected host cells

Back 12

) Inhibiting normal host cell DNA, RNA or protein synthesis. This can cause structural or functional defects in the infected host cell leading to cytolysis or altered cell functions.
2) Causing nicks or breaks in the host cells chromosomes.
3) Changing the antigenic surface of the host cell’s cytoplasmic membrane resulting in it being recognized as foreign and destroyed by the body’s immune defenses.
4) Depleting the host cell of cellular material essential for life or normal function
5) Stimulating body cells to release inflammatory cytokines and chemokines.
6) Stimulating body cells to release inflammatory vasoactive peptides, bradykinines, histamines etc. resulting in vasodilatation and increase mucous secretion.
7) Inducing adjacent host cells to fuse together forming giant multinucleated cells of syncytias as seen with cytomegalovirus (CMV), VZV and HIV.
8) Cell transformation by oncogenic viruses to initiate malignancy.
9) Causing cytolysis of the infected host cell.

Front 13

Question 5: Comment on 2 different ways viruses can evade host immune defenses.

Back 13

Some viruses (e.g. influenza) undergo what is called antigenic drift and shift.

With antigenic drift, mutations cause a gradual change in the virus antigens (e.g. influenza haemagglutinin) preventing adsorption to host cell receptors.
Antigenic shift is caused by a virus (e.g. human influenza) acquiring a new genome segment from a similar virus (e.g. duck influenza). This new genome segment alters the viral antigens and affects the ecotropic range of the virus. Also, Ab against the original virus can no longer bind to or opsonise the new strain of virus because of the altered surface antigens of the virus.
Interfering with MHC-I function: Cytomegalovirus prevents the host from producing MHC-I. Hence CTL cannot recognise it.
Blocking destruction of the infected cell: Epstein-Barr Virus (EBV) code for proteins that blocks apoptosis,
MHC-I structure modification: cytomegalovirus modifies the host to produce MHC-I molecules that cannot present viral epitopes. Hence it is not recognised by CTL and NK cells.

Front 14

Question 6: Give an example of a virus that uses an immune- evasion mechanism and state the mechanism it uses and the disease the virus causes.

Back 14

Epstein-Barr virus (EBV) down regulates host proteins that attach viral epitopes to MHC-I. Interferes with MHC-I function.
-causes infectious mononucleosis and plays a role in certain cancers
-Swollen adenoids (glandular fever)
-Cancer in B-cells: Burkitts lymphoma.
-Nasopharyngeal carcinoma, periodontitis, hairy lekoplakia

Front 15

Question 7: Explain why some viruses actively modify MHC-I and how this affects their ability to survive within the host.

Back 15

Some viruses interfere with MHC-I function.

E.g. Cytomegalovirus and adenoviruses block the formation of MHC-I, so CTLs cannot recognize that the cell is infected and cannot kill it.

Front 16

Question 8: State 3 major components of the immune system targeting viruses and briefly comment on the way in which each component acts against a virus.

Back 16

Production of antibodies (Ab) against the virus. The "tips" of the antibody (the Fab portion) have shapes that have a complementary shape to portions of viral attachment protein and glycoprotein epitopes on the viral surface. When Ab binds the viral epitopes, they block viral adsorption to host cell receptors and, thus, block viral replication. Ab made to virus also opsonise viruses to increase phagocytosis.
Killing of virus-infected host cells by cytotoxic T8-lymphocytes (CTLs). Virus-infected host cells naturally bind viral epitopes to MHC-I and place the MHC-1 with bound viral epitope on the surface of the infected cell where they can be recognized by T-cell receptors (TCR) on the surface of the CTLs. In this way the CTL can target and kill the infected cell by apoptosis or cytolysis.
NK cells recognize infected cells not displaying MHC-I molecules on their surface and kill these cells. Other cells targeted for killing such as malignant cells deficient in MHC-I are also killed by NK cells.

Front 17

Question 1: Give an example of a virus causing:

acute viral infection
chronic viral infection
latent viral infection
slow viral infection

Back 17

a. cold viruses
b. influenza viruses
c. gastrointestinal infections (e.g. rotavirus, Norwalk virus)

a. Hepatitis B
b. Hepatitis C


a. HSV-1 (fever blisters)
b. HSV-2 (genital herpes)
c. VZV

a. AIDS (caused by HIV-1 and HIV-2)
b. Lentiviruses that cause tumours in animals.

Front 18

Define

a) acute viral infection
b) chronic viral infection
c) latent viral infection
d) slow viral infection

Back 18

ii) Viral infections of relatively short duration with rapid recovery.

iii) Viral infections where the virus can be demonstrated in the body at all times and the disease may be present or absent for an extended period of time.

Viral infections where the virus remains in equilibrium with the host for long periods of time before symptoms again appear, but the actual viruses cannot be detected until reactivation of the disease occurs.

Viral infections in which the infectious agents gradually increase in number over a very long period of time during which no significant symptoms are seen.

Front 19

Question 3: Name 4 approaches to diagnosis of viral infections.

Back 19

1) Direct microscopy on tissue samples for CPE (CytoPathic Effect) or the presence of viral antigens
2) Isolation and identification of virus from tissue samples
3) Detection of antibodies to virus or virus antigens in serum (Serodiagnosis)
4) Molecular detection of virus nucleic acid.

Front 20

Question 4: Comment on the major advantage of using serodiagnostic methods as an alternative to direct virion detection for patient with chronic viral infection.

Back 20

During acute illness, when virus is actively shed, virions are relatively easy to detect. But subsequent to the acute phase, it is difficult to detect virions directly in clinical samples. Serology is widely used as an alternative to direct detection methods.
- IgM, which is indicative of recent disease
- Rising antibody titre, using paired blood samples 10 days between the acute and convalescent phase.

Front 21

Question 5: Discuss 3 mechanisms of action of current antiviral drugs.

Back 21

Some antivirals (e.g. amantadine, rimantidine for influenza A) prevent the virus from the uncoating, which is necessary for viral replications.

Others (e.g. zanamivir and oseltamivir for influenza A) inhibit viral surface enzymes involved in budding and release of newly formed viruses from the infected cell.

Most antiviral agents, however, work by inhibiting viral DNA synthesis:
i. Some resemble normal DNA nucleosides, and the virus inserts them into the growing viral DNA strand. Once inserted, these can’t attach and DNA synthesis is stopped. Selectively toxic because viral polymerases incorporate them into their nucleic acid more than host cell polymerases.
ii. Some do not resemble regular DNA building blocks. They bind to an allosteric site that regulates reverse transcriptase activity rather than to the enzymes active site itself as do the above nucleoside analogues. This can prevent formation.

Front 22

Question 6: Name 5 types of viral vaccines.

Back 22

1) Live attenuated vaccines
a. e.g. polio, MMR, TB, Typhoid
2) Inactivated whole vaccines
a. e.g. Rabies, influenza, Cholera, old pertussis
3) Toxoid vaccines:
a. Inactivated toxins such as diphtheria, tetanus.
4) Subunit vaccines:
a. Uses only the antigens that best stimulate the immune response: includes recombinant vaccines (e.g. hepatitis B) and acelluar vaccines (e.g. new pertussis vaccine.
5) Conjugated vaccines
a. Uses LPS to induce T-independent antibody production.
6) Nucleic acid vaccines
a. Injection of ‘Naked’ DNA, triggers CMI, being considered against cancer, some viruses like influenza and HIV.
7) Peptide vaccines
8) Viral vectors

Front 23

Question 7: Briefly discuss the major considerations for development of new viral vaccines.

Back 23

Oral delivery
- Recombinant or cell culture production
- Single dose
- Lifelong protection
- Low toxicity
- High effectiveness
- Low cost
- Low temperature- independent shelf life.

Front 24

Question 8: Give 3 examples of live attenuated viral vaccines.

Back 24

1) Polio vaccine
2) MMR vaccine
3) TB vaccine
4) Typhoid vaccine

Front 25

Question 9: Explain the pattern of antibody production induced by primary and secondary (booster) vaccines with use of a diagram.

Back 25

At the first exposure to a virus it takes several days (2 to 3 days) for the first adaptive immune response to occur. As the virus is removed from the body the memory B and T cells against the strand of virus remain dormant within lymph nodes. When the second exposure to the same virus is detected, the adaptive immune response is now much quicker (immediate) with much increased production of the antigens due to the memory B and T cells.

In medicine, a booster dose is an extra administration of a vaccine after an earlier dose. After initial immunization, a booster injection or booster dose is a re-exposure to the immunizing antigen. It is intended to increase immunity against that antigen back to protective levels after it has been shown to have decreased or after a specified period of time. For example, tetanus shot boosters are often recommended every 10 years.