Patterns of Viral infection

Question 1

Define tropism.

Answer 1

The predilection of viruses to infect some tissues and not others

The tropism of the virus is the place where it replicates.

Question 2

What three factors are tropisms based on?

Answer 2

1. expression of the host cell receptor
2. essential intracellular host cell components
3. extracellular factors required for activation of virus infectivity

Tropism may be determined by the expression of the host cell receptor. HIV enters cells through the CD4 molecule found on T cells.

Tropism may also be limited by the ability of the virus to replicate inside a particular cell type due to abundance or paucity of essential intracellular host cell components. Polioviruses with mutations in their 5’ noncoding regions cannot utilize neuronal host cell factors to translate their mRNAs.

Tropism may also depend on extracellular factors required for activation of virus infectivity. Influenza virus HA protein requires to be cleaved by a host encoded protease expressed in respiratory secretions.

Question 3

Describe the type of tropism exhibited by HIV.

Answer 3

GP120 on HIV interacts with CD4 on the T cell It attaches to co-receptors CCR5 or CXCR4
-tropism switch: virus eveoles to bind to other receptors

Question 4

how are some people resistent to HIV?

Answer 4

• mutation in CCR5 which means they dont make a proper CCR5 receptor
• some who are exposed but are unaffected produce a large amount of chemokine which blocks the use of the co-receptors.

Question 5

Describe the type of tropism exhibited by Measles.

Answer 5

Measles bind to SLAM or CD155 on immune cells when they enter the host They bind to Nectin 4 on airway epithelia when they leave the host

Question 6

Why do measles bind to immune cells>

Answer 6

To hijack a ride to the lymph nodes, so the virus can infect more cells

Question 7

Describe the type of tropism exhibited by Influenza.

Answer 7

Haemagglutinin on influenza binds to sialic acid to gain entry to the cell Sialic acid is ubiquitous so, in theory, influenza can infect all cells Once it’s in the endosome, the low endosomal pH allows a massive conformational change that is required for the virus to fuse with the endosome membrane and uncoat The cleaving of the protein of the virus is essential for the viral genome to gain access to the host cell genetic material So influenza can only infect cells that have the necessary proteases to cleave the protein into 2 The fluid that lines our lungs have these proteases present

Question 8

How can influenza tropism be changed?

Answer 8

Influenza tropism is extended by mutation of the HA cleavage site The mutation could change the cleavage site meaning that more proteases, found in other parts of the body, can cleave the protein

Question 9

At what point does Varicella-Zoster infection become symptomatic?

Answer 9

After the secondary viraemia

Question 10

What is the classic triad of Rubella?

Answer 10

Eye Abnormalities (e.g. cataracts) Deafness Congenital Heart Disease

Question 11

What are some strategies for viral persistence?

Answer 11

evading immune surveilance

• MHC downregulation
• CTL escape by mutation- hep C
• infecting cells with reduced immune surveillance e.g CNS

Question 12

Describe the latency of Herpes simplex virus.

Answer 12

Herpes simplex virus can remain latent on nerve cells and then become activated in an attack of shingles The virus then moves end of the neurones and replicates through the skin (forming a cold sore)

this keeps happening as nerves never die until we do, so the nerves may contain lots of viral genomes which causes epidoses of reactivation

Question 13

Give 5 examples of oncogenic viruses and the types of cancer that they cause.

Answer 13

HHV8/KSHV – Kaposi Sarcoma
HTLV-1 – adult Leukaemia Merkel Cell Polyoma Virus-Merkel Cell Polyoma
HPV –Cervical Cancer
PapilloViruses encode inhibitors of tumour supressor- forces cells into S phase

Question 14

What type of cancer do Hepatitis B and C cause?

Answer 14

Hepatocellular Carcinoma

Question 15

What types of cancer can Epstein-Barr Virus cause?

Answer 15

Burkitt’s Lymphoma Hodgkin’s Lymphoma Nasopharyngeal Carcinoma

Question 16

Give an example of viral load affecting the outcome of an infection.

Answer 16

Second child in a household infected with chicken pox will have a worse infection because they’ll get a large dose from the first child

Question 17

Give an example of co-infections affecting the outcome of an infection.

Answer 17

HHV8 can cause Kaposi Sarcoma in people who are infected with HIV and hence are immunocompromised Hepatitis Delta Virus only infects people with Hepatitis B

Question 18

Give an example of genetic resistance to a viral disease.

Answer 18

• Delta 32 mutation causes the formation of a different CCR5 receptor and so these people are naturally resistant to HIV
• Killer-cell immunoglobin like receptor protein 3 can determine the outcome of hep c infection

Question 19

Give an example of viral sequence affecting the outcome of an infection.

Answer 19

• 2 strains of poli virus may vary in virulence
• a single mutation in the genome can mean one strain acts as a live attenuated vaccine and the other invades the motor neurone and causes paralysis

Question 20

What do these words mean?
Iatrogenic
Nosocomial
vertical
horizontal
germ line

Answer 20

Iatrogenic: due to medical care e.g. contaminated needle
Nosocomial: acquired in hospital
vertical: from parent to offspring
horizontal: all other forms
germ line: part of the host genome

Question 21

How are influenza and rhinovirus spread?

Question 22

How is Hep B and C transmitted?

Answer 22

-nosocomial blood contamination (HIV or hepatitis B or C).

Question 23

How is poxyvirus, papillomavirus transmitted?

Answer 23

-Viruses in skin can be transmitted by direct skin contact, poxvirus, papillomavirus

Question 24

Ebola and dengue transmission?

Answer 24

-Viraemic viruses are transmitted through blood (dengue virus when bitten by an arthropod, Ebola virus)

Question 25

Poliovirus, norovirus and Hep A virus?

Answer 25

Enteric viruses are transmitted through the fecal oral route (poliovirus, norovirus, hepatitis A virus)

Question 26

EBV, cytomegalovirus and mumps

Answer 26

-Viruses may be shed into the oral cavity and transmitted in saliva (human cytomegalovirus, EBV, mumps).

Question 27

what 3 factors determine the capacity of the virus to cause disease?

Answer 27

1. the effects of its replication
2. the strength of the host’s defence system
3. the ability of the virus to spread in and amongst its hosts

Question 28

What are the different outcomes of infection by viruses and examples of each type?

Answer 28

• Acute infection
• Persistent infection
• Latent reactivating infection
• Slow infection
• Oncogenesis

Question 29

example of acute infection and what happens?

Answer 29

Acute infection is the typical expected outcome for influenza.

Rapid production of infectious virus, rapid resolution and elimination of virus by host immune system.

The outcome is determined by intrinsic and innate immunity.

Acquired immunity stimulated after several days mediates final clearance from the host. Memory provides defense against subsequent exposure.

Acute infections frequently cause epidemics. Transmission occurs before symptoms. Inapparent infections (asymptomatic) are common.

Question 30

what are persistent infections?

Answer 30

Persistent infections also have to overcome innate defense at the start of infection. They are not cleared by the adaptive immune response. They may be chronic or lifelong (latent, slow).

Question 31

Examples of persistent infections?

Answer 31

75-85% people infected by Hepatitis C virus will not clear the virus with their CTL response. This may be because the virus rapidly mutates to escape the response by changing its T cell epitopes.
Chronically infected hepatocytes are destroyed by the immune system leading to fibrous scars (cirrhosis).

Question 32

give an example of a latent virus infection

Answer 32

Herpes simplex virus.
The virus first replicates in mucosal or epidermal cells. Perpiheral ganglia become infected and produce a large burst of virus that disappears after 1-2 weeks. The virus establishes a latent infection in terminally differentiated non-dividing neurons of the peripheral nervous system. Since neurons do not replicate their DNA nor divide, the HSV genome survives inside these host cells. The only evidence of the virus is the expression of RNAs known at latency associated transcripts LATs. By this time the infected host is ‘immune’, they have antibodies to their latent virus. Some people reactivate their virus every 2-3 weeks, others experience few or no reactivation events. Stress signals can trigger reactivation. Reacitvation can also be by drugs like glucocorticoids that stimulate transcription but suppress immune responses. Transient production of virions allows spread of the virus across innervated mucosal surfaces to a new host. Then the infected host’s immune response curtails virus production.

Question 33

what type of virus is HIV

Answer 33

retrovirus

Question 34

which cells present CD4

Answer 34

surface of helper T cells, regulatory T cells, monocytes, and dendritic cells

Question 35

DESCRIBE THE hiv replication cyle

Answer 35

Fusion of the HIV cell to the host cell surface.
HIV RNA, reverse transcriptase, integrase, and other viral proteins enter the host cell.
Viral DNA is formed by reverse transcription.
Viral DNA is transported across the nucleus and integrates into the host DNA.
New viral RNA is used as genomic RNA and to make viral proteins.
New viral RNA and proteins move to cell surface and a new, immature, HIV virus forms.
The virus matures by protease releasing individual HIV proteins.