Topic 8: Viruses ✅ Flashcards
Viruses overview
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
What are viruses?
Obligate intracellulaire parasites
-depend on host cells for replication
-use enzymes of host cells to replicate
-can infect eukaryotic and prokaryotic cells
Bacteriophages
Phares
Viruses that infect bacteria
-important pathogenic agents in animals and plants
Virus structure
- Nucleic acid: DNA or RNA
- Capsid for protection
- Envelope (only present in some)
Capsid
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
Capsid shape
Variable
-icosahedral (spherical) symmetry
-helical symmetry
Envelope
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
What do viral genomes consist of?
Double or single stranded DNA
Double or single stranded RNA
2 virus types:
-DNA viruses
-RNA viruses
Where do viruses replicate?
Only in HOST CELLS
Viral Replicative Cycles: stages
- Attachment to the host cell via receptors
- Penetration of virus genome into host cell
- Uncoating of viral genome (aka capsomeres fall apart)
- Replication: viruses uses host replication machinery (enzymes, ribosomes, tRNAs, amino acids, ATP etc) to replicate viral genome and produce viral proteins
- Gene expression: transcription in nucleus and translation is cytoplasm
- Assembly: viral nuclei acid molecules and capsomeres spontaneously self-assemble into the new viruses which are released from the cell
- Release (exit): new viruses released from the cell
- Maturation (enveloped viruses only): when they acquire their envelope
What do Viral Replicative Cycles vary depending on?
Their nucleic acid type and envelopes
- Attachment of virus to host cell
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
- Penetration
Viral entry to host cedll
Enveloped: mostly by membrane fusion (of viral envelope with host cells plasma membrane)
Non-enveloped: by endocytosis
Viral replication in the host cell includes
Replication of the viral genome
Replication of the new viral proteins
DNA Virus Replication
Use same mechanisms as host cells
Replicate using the host DNA polymerase
Viral DNA -> cDNA (multiple copy)
SS RNA viruses
Different categories so different cycles:
-Positive sense: 5->3
-Negative sense: 3–>5
-Retroviruses
RNA viruses use different mechanisms than the host
Retroviruses
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)
What do RNA viruses use to replicate?
The viral enzyme RNA-dependent: RNA polymerase
Viral RNA —RNA polymerase—> viral RNA (copy: use RNA as a template)
Transcription and translation of the viral nuclei acid
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
Translation
The viral mRNA is translated into the viral proteins using the host ribosomes and the translation machinery of the host cell
What does the viral RNA serve as in RNA viruses?
-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
Clarifications on host and viral
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
Viral assembly
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
Viral release from the cell
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)
Retroviruses’ special replicative cycle
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
What is the the only exception to the central dogma of transfer of genetic information?
Retroviruses
Retroviruses: replicative cycle
- Attachment and entry: the viral glycoprotein binds to host cell receptor
- Reverse transcriptase: viral enzyme converts the viral RNA into cDNA (copy DNA)
- 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 - The host’s RNA polymerase transcribes the proviral DNA into RNA molecules
- The viral RNA molecules function:
-as mRNA for synthesis of viral proteins
-as genomes for new virus particles released from the cell - Protease: this viral enzyme cuts the viral polypeptide produced by translation
→Assembly and release from the cell
Lytic cycle
Cell destruction
Lysogenic cycle
Cell not destroyed
Evolution and Origin of viruses
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
Viral diseases in Animals: pathogenicity
Viruses may damage or kill host cells by different mechanisms:
- NON ENVELOPED…
Cause the release of hydrolytic enzymes from lysosomes => cell lysis - BOTH…
Cause the infected cells to produce toxins that lead to disease symptoms - 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) - BOTH…
Inhibition of the host cell replication machinery
Vaccines: control of Animal viral diseases
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)
Emerging viruses that suddenly become apparent
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”
SARS-CoV-2
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
What are the only approved antiviral drugs currently?
Remdesivir: viral RNA polymerase inhibitor-nucleoside analogue
Molnupiravir: viral RNA polymerase inhibitor-nucleoside analogue
Nirmatrelvir/ritonavir: (market name Paklovid) Pfizer protease inhibitor
COVID-19:
-common symptoms
-complications
-transmission
-diagnostic methods
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.
Treatment types for COVID-19
- Anti-viral drugs
- Anti-inflammatory drugs: dexamethasone, corticosteroid drug with anti-inflammatory and immunosuppressive function
-used for patient requiring oxygen support only. - Neutralising antibodies: mimic the immune system and attack the virus.
-only used for non-hospitalized patients in high risk (until 2022)
COVID-19 vaccinations (EU)
Pfizer/Moderna: mRNA vaccines
Johnson & Johnson (Janssen)/ Astra Zeneca: vector vaccines (carrying
viral genes)
-DNA-carrying (more stable)
Novavax: protein subunit
How do the vaccine types produce antibodies?
- mRNA coding a SARS-CoV-2 surface protein
-> viral protein
-> formation of antibodies against SARS-CoV-2 - Recombinant SARS-CoV-2 (subunit vaccine)
-> formation of antibodies against SARS-CoV-2 - Viral vector packaging SARS-CoV-2
-> viral protein
-> formation of antibodies against SARS-CoV-2
What causes the common cold?
Adenoviruses, coronaviruses, rhinoviruses, enteroviruses.
Herpes
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)
VZV
Varicella Zoster Virus
Causes chickenpox in kinds
Causes shingles in adults (herpes zoster)
EBV
Epstein-Barr Virus
Causes infectious mononucleosis (kissing disease)
CMV
Cytomegalovirus
Causes CNS infections (hearing loss, encephalitis)
Ebola virus
Causes haemorrhagic fever (fatal)
HIV Replication cycle
- HIV attaches to CD4 receptor
- Reverse transcriptase synthesises virus RNA into DNA
- Integrase integrates viral DNA into the cell genome (ds DNA) into nucleus
- After integration, transcription resumes
- Viral RNA leaves the nucleus
- Translation in cytoplasm —> VIRUS protein
- Protease cuts up the protein (VIRUS RNA)
- New virus released
HPV
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)
Poliovirus
Causes poliomyelitis (can cause paralysis)
Prevention: Sabin or Salk vaccine
Mumps, measles and rubella viruses
Characteristic Koplik spots
Prevention: MMR vaccine
Mumps virus causes Parotitis disease
Measles virus causes measles
Rubella virus causes Rubella
Hepatitis viruses
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
Major Hepatitis viruses
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
HIV
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)
What is Anti retroviral therapy’s target?
The reverse transcriptase and protease
AIDS
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
HIV transmission
Sexual intercourse:
-sperm/vaginal fluids
Blood:
-e.g. by infected needles/syringes
-blood transfusion
Mother to child:
-during pregnancy
-birth
-breast feeding
HIV diagnosis
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)
AIDS therapeutic strategies
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
AIDS antiretroviral drug types
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
Anti retroviral drug: AZT
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
HIV polymorphism
New strains keep emerging due to the high mutation rate of the HIV
HIV RNA uses reverse transcriptase to become HIV cDNA
Non-conventional viruses
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
Viroids and Prions
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
Prion diseases
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
Prions cause what?
Spongiform encephalopathies
