Viruses - structural diversity Flashcards
Who is the founder of virology?
Martinus Beijerinck in 1899
-filtrate free of bacteria retains ability to cause disease in plant
What contagious living fluid and virus did Martinus Beijerinck discover?
Contagium vivum fluidium
Tobacco Mosaic Virus
Look at diagram on how we study ´viruses slide
What do all viruses contain?
- Viral genome - DNA OR RNA
- Capsid - the protective structural proteins and sometimes viral replicative enzymes. Individual components of a capsid are called capsomeres that are arranged in highly precise and repetitive patterns
-Some have an envelope and attachment spike proteins
Purpose of the ‘wrapping’ or virion
Sculpted to deliver the nucleic acid to particular cell type
What is resolution
What governs our ability to see very small objects
The ability to distinguish between 2 adjacent objects as distinct and separate
Resolving power of light microscope (photons) is about 0.2 micrometres - giant viruses only
Resolving power of transmission electrons microscope - 0.2 nanometres - high resolution due to shorter wavelength of electrons compared to visible light
How much better is transmission electron microscope vs light microscope?
1000 times better resolution
When was the first electron microscope made?
1931 by Ernst and Max Knoll - enabled virus morphology to be observed for the first time
SEM
Scanning
-Sample prep: fix, dehydrate, gold coat
-Any thickness
-Surface view (3D)
-Large field of view
-Lower Resolution (10nm)
-Cells/virions
TEM
-Sample prep: fix, dehydrate, resin embed, section, neg stain
-Must be thin (<100nm)
-Internal morphology (X-section)
-Higher resolution (0.05nm)
-Membranes, organelles, protein complexes
What is Cryo-EM?
A version of EM that freezes many copies of a delicate sample into a glassy state and hits them with an electron beam
-Takes average of many frozen particles in diff orientations to create images into a high-res 3D models of the sample
What distinguishes viroids and prions?
The presence of protein and nucleic acid
Prions - infectious agents composed of RNA and protein alone
What are the 2 types of virus symmetry?
-Helical
-Icosahedral
T4 phages head is icosahedral and tail is helical
What is the most efficient arrangement of subunits in the capsid and why?
Icosahedral symmetry because it requires the smallest numbers of capsomeres to build the shell (3D structure)
Icosahedron- 20 triangular faces, 5 top/bottom, 10 around middle
What is the most common form of a naked virus symmetry?
-Picronavirus - 28nm capsid
-HIV - 100nm capsid
-Smallpox - 200nm capsid
What are all capsid proteins?
20-60kDa
-most have multiples of 60 subunits
What is the T number
(triangular facets per face)
-value given to capture the complexity and size of the virus
–more copies of capsid protein
–more triangular facets per fece, the higher the T number
What shapes are the capsomeres
Pentons or Hexons
look at isohedral viruses
What is present in envelope in viruses
-lipid envelopes
-Contains viral glycoproteins (spikes) for attachment and masking from immune system
-Envelope critical for infectivity - fragile to environmental destruction - detergents/alcohols
What is an example of an enveloped virus and what spikes does this have?
Influenza virus
-Neuraminidase (N) - aids virus to penetrate mucus layer of airways
-Haemagglutinin (H) aids cell attachment and virulence
Circulating human Coronaviruses (mild symptoms)
-HCoV.229E (Alphacoronavirus)
-HCoV-NL63 (Alphacoronavirus)
-HCoV-OC43 (Betacoronavirus)
-HCoV-HKU1 (Betacoronavirus)
What are the novel coronaviruses and what years did they happen?
SARS-CoV (Betacoronavirus) - 2003 10% fatality
MERS-CoV ‘’’’ 2012 30& fatality
SARS-Cov-2 ‘’’’ 2024 - 1.5% fatality
What coronaviruses infect animals only?
Gammacoronavirus and Deltacoronavirus
SARS-CoV-2 structrure
-Long single strand RNA genome of 29 kilobases
-Encodes 29 proteins - only 4 of which are structural proteins (components of virion)
What are the virion structural proteins?
-Spike (S) forms a 600kDa trimeric spike protein
-Membrane (M)
-Nucleocapsid/Ribonucleoprotein (N/RNP)
-Envelope (E)
RNA structure of coronavirus
-have longest RNA genome of any known RNA virus
-genome is 29-30 kilobases of ribonucleotides
-This is wrapped into a ribonucleotide particle (RNP) by multiple copies of the virus encoded N protein
-This approx. 30kb long RNP must be packed into the 80nm diameter lumen of the virus particle
-EM shows single stranded helical RNPs with diameters of approx 15-18nm
What are the packing arrangements of coronavirus?
-‘beads on a string’ - for RNP formation through interactions between virus genomic RNA, nucleocapsid protein, M protein
Tetrahedral arrangements of portions of the RNP promote ellipsoidal virus particles
Hexagonal RNP arrangements promote more circular virions
What is the spike protein?
The virus attachment and fusion protein
What cell receptor binds to the virion Spike protein?
ACE-2 - angiotensin converting enzyme 2
What do the cellular protease TMPRSS2 and Furin aid in?
(transmembrane serine protease 2)
Cleave S1 and S2
Activate the spike
What does Omicron only need to get inside?
Only needs ACE2 so cells without TMPRSS2 are available for infection
What does Omicron have mutations to?
To amino acids in 2 important spike regions
-receptor-binding domains
-N-terminal domain
thus antibodies that would normally neutralise coronavirus do not
