Flashcards in Viruses; Structure, Classification, Replication Deck (40)
What are viruses?
- Small, subcellular (smaller than cells) organisms with an obligate parasitic intracellular lifestyle (can't survive outside cells for long)
- Composed of proteins, nucleic acids (DNA or RNA) and sometimes lipids (stealing cell membrane from host)
- From Latin; 'poison/slime/vermin'
Are viruses alive?
- Cannot reproduce on their own (non-living criteria), but can do so in living cells and can also affect behaviour of host profoundly
- Plays a major role in shaping evolution, including humans (not just negative)
How large are viruses?
- Viruses: 20-100 nm (Smallpox is big at 300nm)
- Bacteria: 1 - 10 μm (10,000nm = 10μm)
- Animal cells: 1 - 100 μm
Where are viruses found?
- Ubiquitous; everywhere (every living organism can host viruses; bacteria, fungi, animals, plants etc.), even other viruses (e.g. mamavirus infected with Sputnik virus)
How many viruses are humans on average infected with?
- At least two different viruses e.g. HSV-1/2, EBV, CMV
Can viruses be transmitted to future generations?
Yes, they can become part of the host genome and be transmitted to future generations
Are viruses always bad?
1) They play a key role in cycle of life in aquatic environments; maintaining equilibrium
2) Can be used to treat bacterial infections (bacteriophage therapy; confers no resistance)
3) 8% of human genome is of viral origin (retroviruses); shaped our evolution and made us into us (but the 8% has no activity)
WHat are the common features of viruses?
- Viral genomes (DNA or RNA) are packaged into particles (not stable on their own), necessary for transmission between hosts
- Viral genome contains information needed for replication within permissive host cell (one that allows viral replication)
- Viral survival esnured by establishing its genome in host cell population
- All viruses are obligate parasites; they NEED the cellular machinery (ribosomes, tRNA etc.) to replicate themselves
What is one way of classifying viruses? (Shapes)
Classified according to their structure and morphology, using the criteria:
- Absence OR presence of an envelope (enveloped vs. naked viruses; arising from hijacking cell membranes)
- Shape of the capsid; protein containing viral DNA or RNA, which is either helical or icosahedral
How many faces does an icosahedron have? Why is this shape preferred?
- 20 identical sides; nearest geometrical shape to sphere
- Spheres have the highest volume/surface ratio; can pack bare nucleic acids w/o too much protein for 'packaging'
- Structure can be built from multiple repetitions of a single protein (only one gene required; gene economy, utilising space inside icosahedron capsid)
What are the rules for viral capsid self-assembly?
Capsids can self-assemble w/o need for additional proteins if:
1) Each subunit has identical bonding contacts w/its neighbouring proteins; usually achieved by symmetrical assemblies of oligomers (mainly pentamers/hexamers/dimers of a single protein)
2) Proteins are linked together by non-covalent bonds; allowing rapid assembly and disassembly of capsid to release nucleic acid
Why is the capsid needed?
1) Provides protection for nucleic acid outside the cell (BUT; needs to be released after entry to host cell too)
> Capsid made from multiple subunits non-covanlently linked (symmetry provides maximal contact between subunits)
> Capsid is metastable 'spring-loaded' during assembly; unfolds in cells like 'bakugan'/Jack in the Box vibes, as conditions change (e.g pH/salt concentration)
2) Provides specific attachment to cell receptors (for naked viruses)
How does the enveloped/non-enveloped nature of viruses affect transmission?
- Sensitive to: dryness, heat, detergents, acids (must stay wet to be transmitted); does not survive in GIT (thus not transmitted by food) e.g. HIV-1
Non-enveloped (much tougher/easier to transmit):
- Resistant to: dryness, heat, detergents, acids, proteases (can remain infective upon drying, transmitted on fomites, survive GIT, and in environment on surfaces) e.g. Adenovirus (cold), Rotavirus (stomach upset)
Protein shell containing the viral genome (RNA or DNA)
Capsid containing nucleic acid
Individual protein molecules which together form the capsid (monomer of capsid)
Lipid bilayer derived from host cells which surrounds the capsid
Additional protein layer located between capsid and envelope in some viruses; same as matrix
A complete, mature infective viral particle outside the cell.
What are the distinct steps of the animal virus life cycle?
- Attachment (docking)
- Transcription (or reverse transcription; generate copies)
- Release & Maturation
How do viruses attach to host cells?
Bind to specific receptors on host cells:
- HIV-1 to CD4 and CXCR4 (co-receptor) on T-cells and macrophages
- Rhinovirus to ICAM-1 on nasal epithelium (Intracellular Adhesion Molecule 1)
- Influenza to sialic acid on respiratory epithelium (hence lung symptoms)
What is cell tropism?
Where the specific viral attachment to host cells results in a preference for specific cell types/tissues (as well as a specific host range)
What is host range? Give examples.
The ability of a virus to infect different species:
- Rabies; wide host range, can infect all mammals
- HIV; narrow host range, can only infect humans
What are zoonotic infections?
Diseases which normally affect animals but CAN infect humans; e.g. swine/bird flu, viral haemorrhagic fever.
Do viruses have preferred routes of entry? Give examples if so.
- Rhinovirus + Influenza = via respiratory tract
- Rotavirus = via GIT
- HIV = via genital tract
What are meant by non-natural routes of entry?
Other routes of entry for virus possible e.g. skin trauma, transplants, blood transfusions/blood products.
Where is a common site for viral attachment, and why?
- Special regions of cell membrane rich in cholesterol and sphingolipids
- More densely packed, rigid regions that are more suitable for stable attachment to cell surface; allowing mechanism of penetration
How does penetration and uncoating occur for enveloped viruses?
- Fusion of viral envelope w/host cell plasma membrane
- Followed by capsid disassembly (uncoating)
>>> Fusion of cell membranes (host - host as envelope is stolen)
How does penetration and uncoating occur for non-enveloped viruses?
- Attachment onto specific receptors of cell surface membrane
- Virus is then endocytosed (in vesicles), and taken into the cell (virus in an endosome - vesicle ting)
- Protein pumps (ATPase?; ATP > ADP) on endosome pump H+ from cytosol into endosome, dropping pH to 4.5
- pH-triggered release of capsid (uncoating)