Topic 8: Viruses ✅ Flashcards

1
Q

Viruses overview

A

Simpler forms of life

Non-cellular infectious particles

DONT CONSIST OF CELLS -> not microorganisms

Much smaller than bacteria (10-300 nm)

Visualises only with EM

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2
Q

What are viruses?

A

Obligate intracellulaire parasites

-depend on host cells for replication

-use enzymes of host cells to replicate

-can infect eukaryotic and prokaryotic cells

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3
Q

Bacteriophages

A

Phares

Viruses that infect bacteria

-important pathogenic agents in animals and plants

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4
Q

Virus structure

A
  1. Nucleic acid: DNA or RNA
  2. Capsid for protection
  3. Envelope (only present in some)
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5
Q

Capsid

A

Protein coat that encloses viral genome

Composed of protein subunits: capsomeres

-encloses and protects from nucleases

-may have fibers that assist the attachment of the virus to the host cells

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6
Q

Capsid shape

A

Variable

-icosahedral (spherical) symmetry

-helical symmetry

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7
Q

Envelope

A

Only present in some viruses (enveloped viruses)
-consists of membrane
-carries glycoproteins

Most animal viruses are enveloped

Function: helps viruses to infect host cells (envelope fusion with host cell)

Comes from host cell’s membrane (cytoplasmic or nuclear)

Formed during exit of viral particles from host cell

->contains combo of viral and host cell molecules

Contains viral glycoproteins which bind to specific receptor molecules on host cell’s surface

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8
Q

What do viral genomes consist of?

A

Double or single stranded DNA

Double or single stranded RNA

2 virus types:
-DNA viruses
-RNA viruses

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9
Q

Where do viruses replicate?

A

Only in HOST CELLS

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10
Q

Viral Replicative Cycles: stages

A
  1. Attachment to the host cell via receptors
  2. Penetration of virus genome into host cell
  3. Uncoating of viral genome (aka capsomeres fall apart)
  4. Replication: viruses uses host replication machinery (enzymes, ribosomes, tRNAs, amino acids, ATP etc) to replicate viral genome and produce viral proteins
  5. Gene expression: transcription in nucleus and translation is cytoplasm
  6. Assembly: viral nuclei acid molecules and capsomeres spontaneously self-assemble into the new viruses which are released from the cell
  7. Release (exit): new viruses released from the cell
  8. Maturation (enveloped viruses only): when they acquire their envelope
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11
Q

What do Viral Replicative Cycles vary depending on?

A

Their nucleic acid type and envelopes

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12
Q
  1. Attachment of virus to host cell
A

Enveloped viruses: glycoproteins on envelope attach on receptors on the host’s plasma membrane

Non-enveloped: fibers or spikes on the capsid attach on the host cell’s membrane receptors

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13
Q
  1. Penetration
A

Viral entry to host cedll

Enveloped: mostly by membrane fusion (of viral envelope with host cells plasma membrane)

Non-enveloped: by endocytosis

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14
Q

Viral replication in the host cell includes

A

Replication of the viral genome

Replication of the new viral proteins

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15
Q

DNA Virus Replication

A

Use same mechanisms as host cells

Replicate using the host DNA polymerase

Viral DNA -> cDNA (multiple copy)

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16
Q

SS RNA viruses

A

Different categories so different cycles:

-Positive sense: 5->3

-Negative sense: 3–>5

-Retroviruses

RNA viruses use different mechanisms than the host

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17
Q

Retroviruses

A

SS RNA viruses

Use the viral enzyme reverse transcriptase and then the host RNA polymerase

Viral RNA —viral reverse transcriptase (RNA template)—> viral cDNA

—host RNA polymerase—> viral RNA (copy- use DNA as a template)

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18
Q

What do RNA viruses use to replicate?

A

The viral enzyme RNA-dependent: RNA polymerase

Viral RNA —RNA polymerase—> viral RNA (copy: use RNA as a template)

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19
Q

Transcription and translation of the viral nuclei acid

A

Viral protein production

DNA viruses: viral mRNA is produced from viral DNA using the host cell RNA polymerase

Viral DNA —transcription: host RNA polymerase (DNA template)—> viral mRNA —translation: ribosomes—> viral proteins

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20
Q

Translation

A

The viral mRNA is translated into the viral proteins using the host ribosomes and the translation machinery of the host cell

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21
Q

What does the viral RNA serve as in RNA viruses?

A

-as mRNA (positive sense RNA viruses)

-as template for production of viral mRNA (negative sense RNA viruses) using viral RNA-dependent RNA polymerase

Viral RNA —viral RNA dependent RNA polymerase—> viral mRNA
—translation: ribosomes—> viral proteins

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22
Q

Clarifications on host and viral

A

Host DNA polymerase= DNA dependent DNA polymerase
->uses DNA as template to synthesize a new DNA strand

Host RNA polymerase= DNA dependent RNA polymerase
->uses DNA as template to synthesize new RNA strand

Viral RNA polymerase= RNA dependent RNA polymerase
->uses RNA as template to synthesize new RNA strand

Viral Reverse Transcriptase= RNA dependent DNA polymerase
->uses RNA as template to synthesize DNA strand

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23
Q

Viral assembly

A

Assembly: viral proteins (capsomeres) assemble to produce new capsids

Capsids then encapsulate new viral genomes to produce new viral particles

Capsomeres —assemble—> capsids
—encapsulate viral genomes—>new viral particles

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24
Q

Viral release from the cell

A

Non-enveloped viruses: released by lysis of the host cell
(lysosomal enzymes)

Enveloped viruses: released by budding => acquire envelope (maturation)

Host cell is destroyed by:
→ the change in the permeability of the plasma membrane (due to the presence of viral proteins)
→ inhibition of the host cell gene expression (the virus “steals” the host enzymes)

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25
Q

Retroviruses’ special replicative cycle

A

Single stranded RNA viruses that use the viral enzyme Reverse Transcriptase to convert their RNA genome into DNA

Eg HIV (Human Immunodeficiency Virus)
-the retrovirus that causes AIDS (Acquired Immunodeficiency Syndrome)

Retroviruses dogma: RNA → DNA → RNA → protein

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26
Q

What is the the only exception to the central dogma of transfer of genetic information?

A

Retroviruses

27
Q

Retroviruses: replicative cycle

A
  1. Attachment and entry: the viral glycoprotein binds to host cell receptor
  2. Reverse transcriptase: viral enzyme converts the viral RNA into cDNA (copy DNA)
  3. Integrase: viral enzyme integrates the viral genome into the host genome
    →The retrovirus cDNA produced is integrated at random into the host genome as a provirus
  4. The host’s RNA polymerase transcribes the proviral DNA into RNA molecules
  5. The viral RNA molecules function:
    -as mRNA for synthesis of viral proteins
    -as genomes for new virus particles released from the cell
  6. Protease: this viral enzyme cuts the viral polypeptide produced by translation
    →Assembly and release from the cell
28
Q

Lytic cycle

A

Cell destruction

29
Q

Lysogenic cycle

A

Cell not destroyed

30
Q

Evolution and Origin of viruses

A

Viruses do not consist of cells => do not fit the definition of living organisms

Origin: nucleic acid fragments released from cellular organisms

Possible sources of viral genomes: plasmids, bacterial and yeast DNA, and transposons (small mobile DNA segments)

There is controversy about whether viruses evolved before or after cells

31
Q

Viral diseases in Animals: pathogenicity

A

Viruses may damage or kill host cells by different mechanisms:

  1. NON ENVELOPED…
    Cause the release of hydrolytic enzymes from lysosomes => cell lysis
  2. BOTH…
    Cause the infected cells to produce toxins that lead to disease symptoms
  3. ONLY ENVELOPED..
    Have toxic macromolecules( e.g. suchasenvelope proteins) and/or change the permeability of the plasma membrane (due to the presence of viral proteins)
  4. BOTH…
    Inhibition of the host cell replication machinery
32
Q

Vaccines: control of Animal viral diseases

A

Consist of dead or inactivated micro-organisms or their products (e.g. proteins/nucleic acids)

Vaccines can prevent certain viral illnesses (as well as certain bacterial illnesses)

Antiviral drugs can help to treat, though not completely cure, viral infections

Disease eradication through systematic vaccination campaigns (e.g. smallpox)

33
Q

Emerging viruses that suddenly become apparent

A

Eg the 2009 flu outbreak (pandemic) caused by the influenza virus strain H1N1
-from Spanish flu

2009 flu pandemic was likely passed to humans from pigs —> originally called the “swine flu”

34
Q

SARS-CoV-2

A

Severe Acute Respiratory Syndrome Coronavirus 2

The virus strain that causes the respiratory illness named coronavirus disease 2019

An enveloped positive-sense ssRNA virus

SARS-CoV (2003), MERS (2012) and SARS-CoV-2 (2019): serious respiratory disease
-another 4 coronaviruses strains: cause common cold

Originated in Hubei province, China, in December 2019

Zoonotic origin: current hypothesis is its passed from bats to pangolins and then to humans

It enters human cells by binding to the receptor angiotensin converting enzyme 2 (ACE-2)

Morphology: Corona (crown) like appearance around a sphere

35
Q

What are the only approved antiviral drugs currently?

A

Remdesivir: viral RNA polymerase inhibitor-nucleoside analogue

Molnupiravir: viral RNA polymerase inhibitor-nucleoside analogue

Nirmatrelvir/ritonavir: (market name Paklovid) Pfizer protease inhibitor

36
Q

COVID-19:
-common symptoms
-complications
-transmission
-diagnostic methods

A

Common symptoms: include fever, cough, fatigue, shortness of breath, loss of smell and taste, loss of appetite, fatigue, sputum production, muscle and joint pains.

Complications: pneumonia, multi-organ failure, or cytokine storm

Transmission: air-borne (via respiratory droplets)

Diagnostic methods:
➢ Real-time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) from a nasopharyngeal swab sample (includes viral particles => viral RNA detection).
➢ Antigen tests (rapid tests/self tests): viral antigen detection from nasal/ nasopharyngeal swab.

37
Q

Treatment types for COVID-19

A
  1. Anti-viral drugs
  2. Anti-inflammatory drugs: dexamethasone, corticosteroid drug with anti-inflammatory and immunosuppressive function
    -used for patient requiring oxygen support only.
  3. Neutralising antibodies: mimic the immune system and attack the virus.
    -only used for non-hospitalized patients in high risk (until 2022)
38
Q

COVID-19 vaccinations (EU)

A

Pfizer/Moderna: mRNA vaccines

Johnson & Johnson (Janssen)/ Astra Zeneca: vector vaccines (carrying
viral genes)
-DNA-carrying (more stable)

Novavax: protein subunit

39
Q

How do the vaccine types produce antibodies?

A
  1. mRNA coding a SARS-CoV-2 surface protein
    -> viral protein
    -> formation of antibodies against SARS-CoV-2
  2. Recombinant SARS-CoV-2 (subunit vaccine)
    -> formation of antibodies against SARS-CoV-2
  3. Viral vector packaging SARS-CoV-2
    -> viral protein
    -> formation of antibodies against SARS-CoV-2
40
Q

What causes the common cold?

A

Adenoviruses, coronaviruses, rhinoviruses, enteroviruses.

41
Q

Herpes

A

Herpesviruses: Herpes simplex virus (HSV-1 and HSV-2)

HSV-1: oral infection (blisters and cold sores)

HSV-2: genital infection (blister and genital sores)

42
Q

VZV

A

Varicella Zoster Virus

Causes chickenpox in kinds

Causes shingles in adults (herpes zoster)

43
Q

EBV

A

Epstein-Barr Virus

Causes infectious mononucleosis (kissing disease)

44
Q

CMV

A

Cytomegalovirus

Causes CNS infections (hearing loss, encephalitis)

45
Q

Ebola virus

A

Causes haemorrhagic fever (fatal)

46
Q

HIV Replication cycle

A
  1. HIV attaches to CD4 receptor
  2. Reverse transcriptase synthesises virus RNA into DNA
  3. Integrase integrates viral DNA into the cell genome (ds DNA) into nucleus
  4. After integration, transcription resumes
  5. Viral RNA leaves the nucleus
  6. Translation in cytoplasm —> VIRUS protein
  7. Protease cuts up the protein (VIRUS RNA)
  8. New virus released
47
Q

HPV

A

Human Papilloms Virus

Cause cervical cancer (types HPV-16/18) and genital warts (benign papillomas; types HPV-6/11)

Sexually transmitted

Prevention measures:
-Vaccination: vaccines Gardasil (types HPV 16/18/11/6) and Cervarix (HPV 16/18) 
-Pap test: cervical smear => detection of morphological abnormalities (e.g. cervical dysplasia)

48
Q

Poliovirus

A

Causes poliomyelitis (can cause paralysis)

Prevention: Sabin or Salk vaccine

49
Q

Mumps, measles and rubella viruses

A

Characteristic Koplik spots

Prevention: MMR vaccine

Mumps virus causes Parotitis disease

Measles virus causes measles

Rubella virus causes Rubella

50
Q

Hepatitis viruses

A

7 different viruses that cause hepatitis (Hep A-G)

Hepatitis: liver inflammation

2 major forms:
-Acute hepatitis: jaundice (characteristic symptom)
-chronic hepatitis: can cause liver cirrhosis and hepatocellular carcinoma

51
Q

Major Hepatitis viruses

A

Hepatitis A virus (ΗAV): RNA virus
-food-borne transmission
-vaccine available 

Hepatitis B virus (HBV): DNA virus
-transmitted by blood and other biological fluids (sexually transmitted disease)
-vaccine available 

Hepatitis C virus (HCV): RNA virus
-transmitted by blood or sexually
-vaccine has not been developed yet

52
Q

HIV

A

Human Immunodeficiency Virus

2 types: HIV-1 and HIV-2 

Infects the Τ- helper lymphocytes (Th-cells) 

Viral glycoprotein gp 120 attaches to the CD4 receptor on the surface of Th- cells causes AIDS (Acquired Immunodeficiency Syndrome) 


53
Q

What is Anti retroviral therapy’s target?

A

The reverse transcriptase and protease

54
Q

AIDS

A

Acquired Immunodeficiency syndrome

HIV carriers remain asymptomatic for years

AIDS onset is <200 Th- cells/mm^3 of blood

Opportunistic infections:
-e.g. candidiasis, toxoplasmosis, pneumonia

Malignant tumours:
-Κaposi sarcoma: malignant tumour of the endothelial cells of the blood vessels
-Burkitt’s lymphoma: Β-cell cancer 


55
Q

HIV transmission

A

Sexual intercourse:
-sperm/vaginal fluids

Blood:
-e.g. by infected needles/syringes
-blood transfusion

Mother to child:
-during pregnancy
-birth
-breast feeding

56
Q

HIV diagnosis

A

Detection:
-the virus can be detected in blood 3-6 weeks after the suspected infection date (window period) depending on the detection method used

Window period:
-virus cannot be detected, low levels in blood, but can still be transmitted

Diagnostic methods:
-detection of anti-HIV antibodies in the blood using ELISA (6-8 weeks after infection)
-detection of viral RNA in the blood using RT-PCR (3 weeks after infection)

57
Q

AIDS therapeutic strategies

A

There is no cure for HIV infection, just prolonging life 

There is no vaccine available due to the high mutation rate of the virus

 Treatment strategies:
- ΗΑΑRT: Highly Active Anti-Retroviral Therapy
- Combination of different types of antiretroviral drugs

Common problems of antiretroviral therapy: toxicity, resistance

58
Q

AIDS antiretroviral drug types

A

Nucleotide analogues:
-inhibit the viral RNA replication by being incorporated into the growing cDNA chain (e.g.AZT)

Non-nucleotide analogues:
-inhibit the activity of reverse transcriptase

Protease inhibitors:
-inhibit the HIV protease which is responsible for the viral polypeptide cleavage and hence the maturation of the new virus particles

59
Q

Anti retroviral drug: AZT

A

Azido-deoxy-thymidine

The next nucleotide cannot be incorporated into the growing DNA chain due the presence of nitrogen (Ν ) instead of -OH 3
=>Inhibits the viral RNA replication

60
Q

HIV polymorphism

A

New strains keep emerging due to the high mutation rate of the HIV

HIV RNA uses reverse transcriptase to become HIV cDNA

61
Q

Non-conventional viruses

A

Viroids: viruses without protein capsid (nucleic acid only)
-infectious nucleic acids that replicate in tissues
-plant pathogens

Prions: viruses without nucleic acid (proteins only)
-small infectious proteins that replicate in tissues
-animal pathogens

62
Q

Viroids and Prions

A

The simplest infectious agents

Viroids:
-small circular RNA molecules
- infect plants => disrupt their growth 

Prions (more important)
- slow-acting indestructible infectious proteins
- Prions propagate by converting normal proteins into prion => aggregation in tissues
-cause serious CNS infections (spongiform encephalopathies) 

Examples of prion diseases: Scrapie disease in sheep, mad cow disease, Creutzfeldt-Jakob disease in humans

63
Q

Prion diseases

A

Mad cow disease: infects cattle (e.g. cows) 
-transmitted to humans by consumption of contaminated beef (cooking does not destroy prions) 
 -causes Creutzfeldt-Jacob disease (CJD) in humans 

Creutzfeldt- Jacob disease (CJD): characteristic of Spongiform encephalopathies
-Spongiform encephalopathies: brain shrinkage and deterioration
-fatal CNS infection by prions 
-symptoms: ataxia, memory loss, convulsions, coma 


64
Q

Prions cause what?

A

Spongiform encephalopathies