Viral infections, oncoviruses & antiviral chemotherapy

Question 1

Dynamics of viral infections
To cause diseases:

Answer 1

Infect their specific host’s cells
replicate efficiently within the host
damage targeted tissues

Question 2

Viral pathogenesis: the process of a virus producing a disease
3 requirments;

Answer 2

Enough virus
Accessible Cells that permits the viral replication
Local antiviral defense/immune system absent or overcome

Question 3

Acute viral infections
(short-term)

Answer 3

Asimptomatic infection
Acute infection

Question 4

Asymptomatic infection
what are the signs and symptoms?

Answer 4

Most virus encounters have no consequence
Many infections are inapparent or asymptomatic

Signs: Evidence of disease that can be observed by others
Symptoms: Apparent only to the patient

Question 5

Acute infection

Answer 5

Viruses can cause acute infections
display short incubation periods upon virus entry into the host.
Rapid onset of disease
Brief period of sympthoms
Quick resolution (elimination of virus by the immune system)

Question 6

The range of clinical manifestations. Factors?

Answer 6

Genetic factors
Age
Comorbidity (other diseases)
Individual immune response

Question 7

Latent or persistent viral infections

Answer 7

Latent infection
Persistent/Chronic infection

Question 8

Latent infection

Answer 8

Latent virus remains in asymptomatic host cell for long periods
No symptoms or viruses are detectable/active
May reactivate due to changes in immunity
Cold sores (e.g. herpes simplex virus, HSV-1), shingles (varicella zoster virus, VZV)

Question 9

Persistent/Chronic infection

Answer 9

A persistent viral infection occurs gradually over a long period;
Hepatitis B virus (HBV )infection, where the virus continue to replicate over time a low level
Not all HBV infections become chronic

Question 10

Herpesvirus – latency

Answer 10

Herpes simplex viruses (HSVs) and varicella-zoster virus (VZV) remain latent in a quiescent but persistent form (latent infection), in neural ganglia cells

Question 11

Primary infection occurs producing:

Answer 11

1. cold sore usually for HSV-1
2. Chicken pox for VZV

Infections produces progeny virions that spread elsewhere
Virus enters innervating sensory neurons, and viruses are transported to the neuronal cell body

Question 12

Where is viral DNA released?

Answer 12

released into the neuronal nucleus and
circularizes (episomal state)

Circular viral DNA persists in the neuronal cell nucleus

Question 13

Herpesvirus – reactivation

Answer 13

HSV-1
Varicella Zooster Virus

Question 14

HSV-1

Answer 14

HSV-1 can periodically reactivate to cause cold sores, in response exposure to sunlight, psychological stress, fever, menstruation and surgical resection

Reactivation in the neuronal cell body
Newly formed capsids are transported to the axonal termini

Infectious virus is released from the axon and infects epithelial cells, resulting in recurrent infection and virus shedding

Question 15

Varicella Zooster Virus

Answer 15

VZV after years of inactivity, may produce the skin disease shingles (herpes zoster)

localised painful and maculopapular rash
in one or two adjacent dermatomes - on trunk

Question 16

Several types of cancer are caused by viruses

Answer 16

develop long after a viral infection
Cancers caused by viruses are not contagious

Question 17

What type of viruses that cause cancer called?

Answer 17

Oncoviruses

Most of them (not all), become integrated into the host cell’s DNA and induce tumours

Question 18

Mechanisms how viruses induce cancer transformation
What can Oncoviruses do:

Answer 18

Encode proteins that act as oncogenes themselves

Activate cellular proto-oncogenes (normal) to oncogenes (hyperactive) - different ways

Inactivate tumour suppressor genes

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Cell cycles are no longer regulated at checkpoints

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Unregulated cell proliferation – cell cycle/division is always on
Genetic/chromosome instability - mutations accumulation in many genes

Question 19

Viruses have been implicated in the genesis of cancers = contribute to 20% of human cancers

Answer 19

info:
Epstein-Barr virus (EBV) - Burkitt’s lymphoma
Hepatitis B virus (HBV) - hepatocellular carcinoma (liver cancer)
Hepatitis C virus (HCV) - hepatocellular carcinoma (liver cancer)
Human herpesvirus 8 (HSV-8) and HIV - Kaposi’s sarcoma (cancer of connective tissue)
Human papillomaviruses (HPV) – Cervical cancer (MAIN ONE*), Head and Neck Cancers, Anal, Oral, Pharyngeal, and Penile Cancer
* Importance of Cervical screening (smear test) – Prevention measure
Human T-cell lymphotropic virus I (HTLV-1) – T cell leukemia
Human T-cell lymphotropic virus II (HTLV-2) - hairy-cell leukemia

Question 20

Isolation and Cultivation of Viruses -

Answer 20

ely on their need to infect cells

Question 21

Viruses can be propagated - labs

Answer 21

Animals (used only before the tests of drugs/vaccines on humans)
Embryonated eggs
Cell cultures

Question 22

Continuous eukaryotic cell lines: cells commercially available (originally derived from donors) with indefinitely ability to _____ in a laboratory.

Answer 22

divide

Question 23

Isolation and Cultivation of Viruses - how are they prepared in a lab:

Answer 23

• grow = in plates similar to petri dishes and sample containing viruses are added to allow virus to attach to the cells and then removed
• cell covered with agar to block diffusion of viruses
• virions progenies produced by a single cell could only infect surrounding cells
• RESULt - localised area of cell destroyed 9viral plaques) detected using a dye to stain just the viable cell
• cells of plaque not retain the dye
• each plaque corresponds to an area of cells infected and dead by single virus; expressed as plaque-forming units (PFU)

Question 24

Vaccinations
- prevent viral infections/ severe diseases

Answer 24

• possible infection and/or subsequent illness when they come into contact with the respective pathogens
• developed vaccines (e.g. providing dead/attenuated viruses or proteins or mRNA to trigger a specific immune response)
• Some viral diseases, often deadly have been eradicated (e.g. Smallpox) or almost eradicated (e.g. Poliomyelitis caused by poliovirus)

Question 25

Antiviral drugs - to treat specific viral infections

Answer 25

A drug interfering specifically and selectively with the virus replication (effective) with no/low effects on the host cell activity

Question 26

What are the 6 steps of viral replication??

Answer 26

1) Attachment of virus

2) Penetration

3) Uncoating

4) Genome replication

5) Protein synthesis, protein maturation and virion assembly

6) Genome replication

Question 27

Human Immunodeficiency Virus (HIV)
Lifespan chronic infection

Answer 27

HIV belongs to the Retroviridae family, classified into two subtypes: HIV-1 and HIV-2. HIV-1 is more virulent and more infective

Viruses that insert a copy of its RNA genome into the host cell’s genome

Question 28

HIV causes acquired immunodeficiency syndrome (AIDS)

Answer 28

progressive failure of the immune system (decreasing CD4+ T-lymphocyte count) allows life-threatening opportunistic infections (e.g. Criptococcus) and cancers (oncovirus) to thrive

Question 29

HIV infection progresses in 3 stages:

Answer 29

1) Acute HIV = flu-like symptoms that occur days to weeks after contracting HIV

2) Chronic HIV= the latent and asymptomatic stage that can last several years

3) AIDS: occurs when CD4 cell count falls below 200 cell/mm3. This makes people vulnerable to opportunistic infections and AIDS-defining conditions

Question 30

Does HIV need to be treated?

Answer 30

HIV infection is not treated, the median time from infection to the development of AIDS is 8-10 years.
HIV infection NEEDS to be treated.

Question 31

HIV Combinational therapy (cART/HAART)

Answer 31

The highly active antiretroviral therapy (HAART

Question 32

Explain HAART treatment

Answer 32

treatment regimen typically comprised of a combination of two/three antiretroviral drugs with different mechanisms of action

Different mutations are required to develop drug resistance to all drugs
Reduced risk of drug resistance

Question 33

Principle of combination therapy

Answer 33

Combining different antiviral drugs with distinct mechanisms of action having a proved synergistic activity against HIV

Question 34

The goals of HAART in patients with HIV infections :

Answer 34

1. Reduce plasma viral RNA to an undetectable level
2. Prevent or reduce drug resistance
3. reduce morbidity and mortality
4. Prevent HIV transmission