Viruses Flashcards
What is a virus?
Ultramicroscopic infectious agent that replicates itself only within cells of living hosts; many are pathogenic; a piece of nucleic acid (DNA or RNA) wrapped in a thin coat of protein.
Where did viruses come from?
- Regressive evolution: degenerate life-forms which have only retained essential genetic information for their parasitic way of life.
- Cellular origins: sub-cellular macromolecules which have escaped their origins inside cells.
- Independent entities: evolved from self-replicating molecules from the RNA world. Separate from cellular organisms.
What is the RNA world hypothesis?
- A world filled with life based on RNA predates the current world of life based on DNA and protein.
Describe an example where a virus is not ‘bad’.
- HERV-derived proteins, such as syncytin, have become necessary for normal human placental function.
List a few characteristics of viruses.
- Not cells
- A genome surrounded by a protective protein coat
- Dependent on host for cellular machinery
- Intracellular parasite
- Formed form assembly of newly synthesised components made in host cell
What are viruses made of?
- Contain genome with DNA or RNA, ss or ds, packaged in a protective protein coat or capsid
- May also have an envelope made of cell membrane modified to contain virus proteins
How has international committee on taxonomy of viruses grouped viruses?
- Grouped based on genome (nucleic acid type, fragmentation, organisation, sequence), strategy for replication (reverse transcription, integration, site of replication, morphology (envelope..)
What are 4 types of distinguishing structures a virus may possess?
- Icosahedral protien coat, helical protein coat, viral envelopes, complex symmetry
What are the features of an icosahedral coat?
- Repeating units of protein (capsomers) or may be subunits of protomers (all together is called capsid)
- 12 vertices and 20 equilateral triangles
- 2, 3 and 5 fold axes of symmetry
- usually pentons and hexons detected
What are the number type of symmetry a virus can have? Give an example of a virus with a particular axes of symmetry.
- 2-fold, 3-fold, 5-fold (odd numbers?)
- Icosahedral adenovirus capsid has 3 rotational symmetry of axes. (causes respiratory illness or conjunctivitis)
What are the features of a helical protein coat? Give a few examples of a viruses with this feature.
- rod shaped coat consisting of repeating units
- a single protomer associates with nucleic acid in a spiral or helical arrangement
- ebola virus, rabies virus, measles virus
What are the features of a viral envelope? Give a few examples of viruses with this feature.
- Icosahedral or helical nucleocapsid surrounded by a membrane
- A host derived lipid from intracellular membrane ( nuclear, endoplasmic reticulum, golgi or plasma membrane
- Contains virus-encoded proteins or glycoproteins (spikes)
- May be flexible (pleiomorphic)
- influenza virus, herpesvirus, measles virus, SARS-CoV virus
Which virus has the most complex symmetry?
- Poxviruses are the largest and most complex with more than 100 different proteins in the virion and the genome is 130 kbp dsDNA
- Vaccinia virus and bacteriophage also have complex symmetry
What are the forms of viral nucleic acid a virus can have?
- ss DNA or RNA
- ds DNA or RNA
- Sometimes can be divided into segments
- ssRNA can be +ve sense (like mRNA) or -ve sense (complementary to mRNA)
What is virus classification based on? (not the same as taxonomix groupings)
- Based on epidemiologic/pathogenic criteria
- Grouped into enteric viruses or respiratory viruses or arboviruses or sexually transmitted viruses or hepatitis viruses
What are features of enteric viruses? What are a few examples of these viruses?
- Replicate primarily in and are localised to the intestinal tract
- Acquired by ingestion of material contaminated with faeces
- rotavirus, calicivirus, astrovirus, some adenoviruses
What are features of respiratory viruses? What are a few examples of these viruses?
- Replicate primarily in and are localised to the respiratory tract
- acquired by inhalation of droplets
- rhinovirus, coronaviruses, adenoviruses, orthomyxovirus
What are features of arboviruses? What are a few examples of these viruses?
- Infects insects that ingest vertebrate blood
- replicate in the insect and are transmitted by bite
- orbivrus, flaviviruses, togaviruses
What are features of sexually transmitted viruses? What are a few examples of these viruses?
- include some herpesviruses and papillomaviruses that cause lesions in the genital tract
- also certain retroviruses and hepatitis viruses that are transmitted during sexual activity but can cause generalised disease
What are features of hepatitis viruses? What are a few examples of these viruses?
- principal target organ is the liver
- hepatitis A and E (spread via enteric route) and B, C and D (spread by blood or sexually)
What can virus receptors be made of? Give a few examples.
- protein (ICAM-1 for most rhinoviruses; ACE2 for SARS-CoV-2)
- carbohydrate (sialic acid for influenza virus)
- Viruses can use 2 different receptors on the same host cell (initial attachment and closer attachment)
What are two ways in which a virus can enter the host cell?
- fusion or endocytosis
- Viruses can uncoat at plasma membrane or within endosome or after endocytosis, uncoat at the nuclear membrane
How does fusion occur between virus and host cell?
- The viral envelope and the cell membrane must mix and form a pore for the nucleocapsid to be released.
Which virus uncoats at the plasma membrane?
- HIV contents are released directly into cytoplasm.
Which virus enters through endocytosis?
- Alphaviruses (ross river virus) initially taken into the endosome before fusion
- Release from endosome is triggered by the low pH of the vesicles
How is the viral genome amplified in the host cell?
- Nucleic acid replication produces new viral genomes for incorporation into progeny virions
- mRNA is transcribed from viral DNA and codes for viral proteins that are translated by host
Where do DNA and RNA viruses replicate?
- DNA virus replicates in nucleus (except pox)
RNA viruses replicate in cytoplasm (except flu)
What special enzyme is used to copy DNA to DNA in us?
- DNA-dependent DNA polymerase (DpDp)
What special enzyme is used to transcribe DNA to mRNA in us?
- DNA-dependent RNA polymerase (DpRp)
What can’t our special enzymes do? What is significant about this?
- copy RNA to RNA
- copy RNA to DNA
- all RNA viruses must encode for their won RNA-dependent polymerase (RdRp) to copy RNA to RNA or RNA to DNA as we don’t have those machinery
What do RdRps require for replication?
- require a template, always generate a copy 5’ to 3’, generally form a dsRNA replication intermediate
How does -ive sense viruses replicate within host? Why is it different from +sense viruses?
- They cannot be recognised by host genome (like influenza) so its RdRp must be carried in with the virus particle.
- It needs to do this to first copy it’s negative sense genome into mRNA
- This is also true for dsRNA viruses who need to initially make the ss mRNA for translation
Which virus uses reverse transcriptase and what does it do?
- An enzyme required by Retroviridae
- It can copy RNA to DNA, digest RNA and copy DNA to DNA
- Enables viruses like HIV to integrate their RNA genome into the host DNA chromosome
What is required for post-translational cleavage of polyproteins of viruses?
- virus-encoded proteases but also some host-encoded proteases
Where does glycosylation of envelope glycoproteins of virsuses occur?
- in rough endoplasmic reticulum and golgi vesicles of host cell
What do all non-enveloped animal viruses have?
- An icosahedral structure
What are the strategies for assembly and release of non-enveloped animal viruses?
- Spontaneous assembly of capsid proteins around the nucleic acid genome
- Proteolytic cleavage to induce final conformation in the capsid proteins of mature infectious virions. (carried out of host or viral prteases)
- Accumulation of virions in cytoplasm or nucleus wait until cell lyses to be released.
What are the strategies for assembly and release of enveloped viruses?
- Release may take place by budding from cell surface
- membrane surrounding nucleocapsid bulges out and becomes ‘nipped off’ to form new enveloped virion
- Some enveloped viruses use the cellular secretory pathway to exit (through golgi vesicles)
What are some possible effects of animal viruses on cells?
- Transformation of normal cells to tumor cells
- Lytic infection
- Persistent infection
- Latent infection
What must viruses do to cause infection?
- gain entry into body
- multiply and spread
- target appropriate organ
What must viruses do to be maintained in nature?
- spread into the environment (cough, sneeze) or
- taken up by an arthropod vector or needle or
- passed congenitally
What are ways a respiratory virus can be transmitted?
- droplets produced by coughing, sneezing, talking
- direct contact with infected individual
- contact with contaminated surface, touch mouth or eyes or nose
How does a virus enter through the alimentary tract (gastrointestinal tract)
- ingested virus is swallowed or infect oropharynx and be carried elsewhere
- Constant movement of contents in intestinal tract allows some virus to contact specific receptors
- These viruses are usually acid and bile resistant and generally do not have an envelope (membrane bilayer is easily destroyed by acid/bile)
- HIV can infect rectal route
Which alimentary viruses infect the mouth or oropharynx?
- Herpes simplex virus 1 (cold sores): acquired by direct contact of infected saliva with damaged skin
- Epstein-Barr virus (infectious mononucleosis): acquired by direct contact of saliva with oropharynx (kissing)
What are the mechanisms of spread of virus in the body?
- Local spread on epithelial surface eg. herpes
- Sub-epithelial invasion and lymphatic spread
- Sub-epithelial invasion and neuronal spread eg. rabies
- Spread via bloodstream (viraemia)
What is disseminated and systemic infection?
- Spread beyond primary site
- many organs infected eg. ebola
How does viraemia work? Give a few examples.
- Virus can be free in plasma eg. arboviruses, neurotropic viruses
- either produced by infected vascular endothelium or released in large amounts from secondary lymphoid tissues (liver, spleen)
- Neutralised by developing Ab response and removed by macrophages (1-2wks)
- Virus can be cell-associated eg. measles spread by monocytes
- can persist from months to years if viral genomes latent to avoid CTL attack
What are ways virus can be shed into the environment?
- Respiratory, faeces, skin, blood, urine, milk, genital secretions
What is a cytocidal virus? Give an example.
- disease may result directly from the cell death caused by viral replication
- influenza virus infection
What is a non-cytocidal virus? Give an example.
- cells may lose ability to perform particular functions
- SARS-CoV-2 and ACE2
What are consequences of immune response?
- Immunopathology (fever, inflammation, enlarged lymph nodes, killing of infected cells)
- Immunosuppression (virus grows in cells of immune system eg. HIV)
What does cytokine release syndrome increase?
- immune activation, IL-6 and others, vascular permeability, inflammatory monocytes and neutrophils, liver/kidney damage, hypoxia, mechanical ventilation, death
What are the outcomes of virus infection?
- fatal (man is not natural host, high mortality rates) eg. ebola
- full recovery (completely cleared by immune system) eg. influenza
- recovery but permanent damage (virus cleared but left with symptoms) eg. cancer
- persistent infection (virus not cleared and can resurface to cause disease)
Why can we get some diseases repeatedly?
- ineffective immunity eg. warts
- effective immunity but multiple serotypes of virus eg. rhinovirus
- constantly evolving virus eg. influenza, HIV
What are ways which viral genomes repeatedly change?
- mutation (nucleic acid copying errors)
- If 2 viruses infect same cell, recombination (exchange of nucleic acid sequence) or reassortment ( swapping of segments for viruses that have segmented genomes)
- Antigenic drift resulting from RNA copying errors which give rise to new seasonal epidemic strains (influenza)
- Antigenic shift resulting from genetic reassortment give rise to pandemic of influenza
What is an example of a latent infection?
- varicella-zoster virus (chickenpox and shingle)
- Immunodeficiency virus (AIDS)
