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N) Therapeutics [term 2] > Virology - Viral classification, Structure and Replication > Flashcards

Virology - Viral classification, Structure and Replication Flashcards

1
Q

What is a virus?

A
  • Smallest replicating organism.
  • Nucleic acid enclosed in a protein coat.
  • No metabolic processes. [not on its own, it needs a host, not within a host? no metabolic processes it depends completely on the host for that]
  • Small, infectious obligate intracellular pathogen.
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2
Q

Viral classification

A

Classification: the process of grouping biological pathogens, based on similar features that viruses have in common

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3
Q

Two classification systems used in Virology:

A
  1. International Committee of Taxonomy of Virology ( ICTV)

2. Baltimore classification

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4
Q

Viral Classification: History of taxonomy

A

Initially,
There was no system and there was haphazard naming
E.g. According to the disease – rabies, hepatitis viruses
E.g. according to the cause – influenza
E.g. According to the body site – rhinovirus
E.g. According to the area, it was discovered – Rift Valley fever virus
E.g. According to the person who discovered it - the Epstein-Barr virus (EBV)

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5
Q

History of taxonomy in the ’60s

A

Then, in the ’60s

  • Advent of electron microscopy
  • Deciphered more information about viruses – e.g. structure, shape, composition
  • Realized the complexity and diversity of them
  • They don’t fit neatly into existing classification systems for cellular organisms

=A new hierarchical system was developed:

- Nature of the nucleic acid in the virion
- Symmetry of the protein shell
- Presence or absence of a lipid membrane
- Dimensions of the virion and capsid
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6
Q

History of taxonomy in the ’70s

A

Then, in the 70s

  • Advent of sequencing technologies
  • Genomics started to play a role in taxonomy
  • The classification, therefore, needed adjusting and reclassifying
  • The International Committee on the Taxonomy of Viruses (ICTV) was developed
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7
Q

International Committee on the Taxonomy of Viruses (ICTV)

A
  • ICTV deals with viral species in a polythetic fashion [looks at any characteristics before grouping and classifying]
  • Requires consideration of various properties of viruses
  • A group of virologists has to rationalize the assignment properties to group viruses
  • The system evolves over time as more information becomes available
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8
Q

Nomenclature in ICTV

A

Suffixes are given for the various taxa

  1. Order - virales
  2. Family - viridae
  3. Subfamily - virinae
  4. Genus - virus
  5. Species - No specific suffix
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9
Q

Example 1 of the Nomenclature in ICTV

e.g Human Respiratory Syncytial Virus

A

The formal description of Human Respiratory Syncytial Virus

This virus belongs to the -
Order :Mononegavirales, 
Family: Paramyxoviridae, 
Subfamily: Pneumovirinae, 
Genus: Pneumovirus, 
Species: Human respiratory syncytial virus
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10
Q

Example 2 of the Nomenclature in ICTV

e.g Severe acute respiratory syndrome- Coronavirus 2(SARS-CoV 2)

A

The formal description of Severe acute respiratory syndrome- Coronavirus 2(SARS-CoV 2)

This virus belongs to the 
Order: Nidovirales, 
Family: Coronaviridae, 
Genus: BetaCoronavirus, 
Species: SARS CoV 2 virus.
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11
Q

Key fact on viruses that make life easier:

A

All viruses on the planet follow this rule, no known exception.

Viral genomes must make mRNA that can be read by the host ribosomes

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12
Q

Baltimore Classification

A

Based on:

  • Nature of genome (DNA vs RNA)
  • Polarity of the genome (positive vs negative sense)
  • Reverse transcription (Yes or no)
  • Based on the nature of the pathway from nucleic acid to mRNA synthesis

Central Dogma is:

DNA–> RNA–> Protein
If it is reverse [RNA –> DNA] it is known as reverse transcription, because it goes against the central dogma [DNA –> RNA]

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13
Q

Baltimore classification groups

A

Divided into 7 groups.

  1. dsDNA –> mRNA transcribed directly from DNA
  2. ssDNA –> ssDNA 1st converted to dsDNA then mRNA
  3. dsRNA –> and mRNA can be transcribed from the RNA genome
  4. ssRNA + –> mRNA directly from RNA genome
  5. ssRNA (-) –> mRNA directly from RNA genome.
  6. ssRNA –> use reverse transcriptase to make DNA from the RNA. Then from the DNA, we transcribe mRNA.
  7. dsDNA –> RNA intermediate mRNA or template to make mRNA.
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14
Q

Viral structure overview

A
  1. Principles viral Structure
  2. Nomenclature in virus structure
  3. Functions of a virion
  4. Methods of studying the viral structure
  5. Capsid symmetry
    • Helical Symmetry
    • Icosahedral symmetry
    • Self-assembly
  6. Viruses with envelopes
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15
Q

My learning goals in terms of Viral Structure

A
  • Understand virus structure
  • Be able to label a diagram of an enveloped virus
  • Definition of viral structure nomenclature
  • Function of the structural proteins in relation to the function of the virion.

-Structural difference between enveloped vs non-enveloped viruses and how this impacts other biological properties.

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16
Q

Viral Structure

A

Inside –> out

  1. Viral genome
  2. Nucleocapsid
  3. Viral tegument
  4. Envelope
  5. Envelope protein -usually glycoproteins
17
Q

The nomenclature used in virus structure

A
  1. Subunit = Single, folded polypeptide chain
  2. Structural unit = Unit from which capsid or nucleocapsid are built (may be made up of one more protein subunits)
  3. Capsid - Coat = Protein shell surrounding the viral nucleic acid
  4. Nucleocapsid - Core = Nucleic acid-protein assembly packaged within the virion.
  5. Envelope - Viral membrane = Host cell-derived lipid bilayer with viral glycoproteins
  6. Virion - viral particle = Infectious viral particle
18
Q

Principles of viral structure

A

-Viral particles (virions) are made up of structural proteins and nonstructural components eg. enzymes

  • *The primary function of a virion:
    1. Protect viral genome
    2. Effective transmission of the viral genome from one host cell to another
  • Viral particles (virions) are designed to protect the viral genome.
  • Genetic economy dictates the construction of capsids from small subunits
19
Q

Virus capsid

A
  • All viruses possess a capsid or nucleocapsid (aka ‘core’)
  • Most viral particles appear rod-shaped or spherical under EM ( Watson and Crick)
-Small coding capacity of viral genomes- capsid constructed from a small number of proteins, regularly and repetitively arranged:  
>Maximal contact
>Non-covalent bonds
>Results in a symmetrical structure:
   1. Helical symmetry
   2. Icosahedral Symmetry
Capsomere: = 
#Regardless of their structural complexity, all virions contain at least one protein coat- capsid or nucleocapsid.  The repetitive arrangement of a limited amount of proteins allows the construction of a symmetrical structure.
20
Q

Helical symmetry

A

Nucleocapsid of most viruses are rod-shaped or filamentous structures with helical symmetry.

  • Examples: Influenza, Measles, Rabies
  • All helical animal viruses happen to have ss RNA genomes, and all are enveloped
  • Looks filamentous or rod-like
  • Open structure – can enclose any volume by varying the length
  • The longer helical particles can curve or bend – strength through flexibility
21
Q

Icosahedral symmetry

A

Icosahedron 20 triangular faces and 12 vertices related by two, three, and fivefold axes of rotational symmetry. Most closed capsids appear spherical and often have prominent surface structures or glycoproteins in the envelope that don’t conform to the underlying icosahedral symmetry of the capsid shell.

  • Examples: Herpesviruses, adenovirus, picornaviruses
  • Closed structure- restricted volume
  • An icosahedron is a shape consisting of 20 triangular faces arranged around a sphere
  • Most icosahedral viruses are made of 60 protein subunits (3 subunits (i.e. a trimer) per face). This is the simplest conformation, and each subunit binds with the neighbors identically
22
Q

Other capsid architectures [complex]

A

-Most viruses are helical or icosahedral
-Some exceptions to the rule:
Retroviridae
Poxviridae

23
Q

Envelopes

A

Many viruses have structural elements in addition to the viral capsid- viral envelopes vary in morphology, structural complexity, and size. The envelope forms the outermost layer. Lipid composition differs from different cellular membranes.

Some viruses exit the cell without destroying it
They instead ‘bud’ from the surface of the cell, acquiring a lipid envelope in the process.

Embedded in the envelope are:

  1. Transmembrame proteins
  2. External proteins
##The protein coat of most viruses displays helical or icosahedral symmetry. 
Irrespective of whether they are enveloped or non enveloped
24
Q

Transmembrane proteins and External proteins.

A
  1. Transmembrane proteins [pass through membrane]
    >Contain hydrophobic domains
    >Form a channel through the envelope e.g. ion channels
    ?Enables the virus to control the permeability of the membrane
    >E.g. influenza M2 protein
  2. External proteins
    >Sits outside the membrane, but anchored with a transmembrane domain
    >May be glycosylated – glycoproteins

> Important:

  • Major antigens
  • Receptor binding
  • Membrane fusion
  • haemagglutination [clumping of virally infected cells]
25
Q

Viral replication

A
  • Viruses like other organisms need to replicate
  • The biological purpose of viral replication cycle is to generate new viral genomes and proteins

-In order to continue their infectious cycle and spread to a new host

-The replication strategy of viruses is dependent on the coding capacity of the genome:
>Small viruses e.g. parvovirus - heavy reliance on host cell
>Large virus e.g. poxviruses – encode most of the information required for replication. Only needs the cells for its machinery e.g. ribosomes

26
Q

Overview of viral replication

A
  • Most RNA viruses replicate in the cytoplasm( except Influenza and HIV)
  • Most DNA viruses replicate in the nucleus ( except Poxvirus)
  • Viruses attach to the host cell, enter, release the genome (uncoating), replicate the genome, express whatever structural or non-structural proteins are required, self assemble, and then exit.
27
Q

A basic representation of the viral replication:

A
  1. Slide 30.
28
Q

Attachment

A

The first cell surface molecule essential for viral attachment is called its receptor
Virus particles bind to host cell receptors to initiate entry
Viruses may use more than one receptor – i.e. infect different types of cell
Viruses may use a receptor and a co-receptor

29
Q

Attachment HIV as an example.

A

Example: HIV binds to the CD4 cell receptor and then requires an additional co-receptor such as CXCR4 for entry.

  • The cell receptor may determine the tropism of viruses (i.e. the type of cell its ability to replicate in) and the host range
  • Binding of virions to cell receptors may activate signaling pathways and facilitate viral entry
30
Q

Entry into the cell and uncoating

A

Via Endocytosis and through fusion.

Uncoating: Partial or complete removal of the capsid, exposing genome

31
Q

The central dogma of molecular biology

A

DNA –> mRNA –> Protein are made structural and non-structural to make new viruses.

32
Q

Summary Baltimore Classification - Transcription and Translation

A

-Transcription: the process of transferring the information encoded in the base sequence of a template nucleic acid molecule to another. It can be either the formation of mRNA from DNA or the production of a complementary strand from single-stranded RNA. The enzymes involved are DNA-dependent RNA polymerase, RNA-dependent RNA polymerase, and RNA-dependent DNA polymerase (reverse transcription).

-Translation: the process of making a protein chain from the information in the mRNA. The four-letter language of the nucleic acid (sequence of bases) is translated into a 20-letter protein
(sequence of amino acids).

33
Q

Assembly and Maturation

A

Assembly = Collection of all the components necessary for the formation of a mature virion

Maturation = Is when the virus becomes infectious

  • Involves structural changes of the viral particle
  • Frequently requires cleavage of larger proteins into smaller ones - usually requires proteases
  • Some viruses mature within the cell. Some mature after release from the cell.
34
Q

Release

A
  1. Lytic release
    - Infected cell breaks open and releases the virus
    - Usually non-enveloped viruses
  2. Budding
    - Virus buds through cell membrane or an intracellular vesicle to acquire an envelope
    - May (e.g paramyxoviruses) or may to (e.g hepadnaviruses) be damaging to the cell.

N) Therapeutics [term 2] (2 decks)

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