MODULE 3

MCB 102

LECTURE

MODULE 3: virus structure, components, function

DEFINITION OF TERMS

  1. subunit
  • single folded polypeptide chain
  • CAPSOMERE
  1. structural unit (protomer, asymmetric unit)
  • one or more subunits
  • unit from which capsids or nucleocapsids are built
  • CAPSID
  1. capsid (“box” in latin)
  • protein shell surrounding the genome
  1. nucleocapsid (core)
  • nucleic acid and protein assembly within the particle
  • used when substructure is discrete
  • nucleic acid + capsid
  1. envelope (viral membrane)
  • host-cell derived lipid bilayer
  1. virion
  • infectious virus particle

virion size

average size: 10 – 300 (or 400) nm in diameter

comparison

  • Nanometer: 10-9 meters = 10 angstrom = 0.001 microns
  • Alpha helix in protein: 1 nm in diamter
  • DNA: 2 nm in diameter
  • Ribosome: 20 nm in diameter
  • Poliovirus: 30 nm in diameter
  • Pandoravirus: 1000 nm in diameter

2003 - mimivirus

  • Giant MIMIVIRUS was described but was sequenced in 2004

2011 – megavirus chilensis

  • Megavirus chilensis was discovered
  • largest virus
  • 440 nm
  • most complex genome with 1.2 Mb

2013 – pandoravirus

  • infect amoeba
  • larger than some bacteria
  • size: 1.0 um / 1000 nm
  • genome 2.8 Mb

comparison – PITHOVIRUS SIBERICUM

  • SIZE: 1.5 UM / 1500 NM
  • GENOME: 0.6 Mb

SUMMARY OF VIRAL STRUCTURES

  1. VIRION
  2. CAPSID/PROTEIN COAT
  3. VIRION SYMMETRY
  4. VIRAL GENOME
  5. VIRAL PROTEINS
  6. ENVELOPE
  7. VIRAL CARBOHYDRATES
  8. OCCLUSION BODIES

structure of viruses

PROTOMER

  • Basic protein building block of the capsid

CAPSOMERE

  • Morphological unit on the surface of the virus
  • Either 5 protomers (PENTAMER) or

6 protomers (HEXAMER)

VIRION SYMMTERY

  1. Helix
  2. Icosahedral
  3. Rod
  4. Cone

Note: most common are helical and icosahedral

VIRION

  • Complete virus particle that represents the extracellular phase of the virus life cycle
  • FUNCTIONS:
  1. Protects the genome
  2. Delivers the genome
  3. Delivers protein contained in the virion
  4. Interacts with the host

CAPSID/PROTEIN COAT

  • Constructed from many copies of one or few types of protein subunits (protomers)
  • CAPSOMERE: subunit (self assembles to form the capsid)
  • CAPSID: structural unit
  • FUNCTIONS:
  1. Protects the genome
  2. Recognizes and interacts with the host cell
  3. Facilitates the transfer of the viral nucleic acid
  4. Determines the antigenic characteristic of the virus

VIRION SYMMETRY

ICOSAHEDRAL (CUBIC)

  • 20 FACES (each an equilateral triangle)
  • 12 VERTICES (where the vertices of 5 triangles meet)
  • 30 EDGES (each of which the sides of two triangles meet)

capsids with icosahedral symmetry

  • Exemplified by many common plants and animal viruses
  • Constructed from identical protein molecules
  • Pentamers are found at the VERTICES
  • Hexamers are found at the FACES

ADVANTAGES of icosahedral symmetry

  1. Allows tight-packing of subunits
  2. Subunits can be smaller (focus on genetic info)
  3. Most efficient arrangement of subunits in a closed shell

(smallest number of subunits used to build a shell)

HELICAL

  • Nucleic acid is coiled in the form of a helix
  • Protein subunits are arranged helically like hollowed cylinders around a coil
  1. RIGID in plant virus
  2. LONG AND FLEXIBLE in animal viruses
  • SIZE is determined by both NUCLEIC ACID and CAPSOMERES
  • DIAMETER is dependent on SIZE and SHAPE PROTEIN INTERACTION
  • LENGTH is determined by LENGTH of NUCLEIC ACID

viruses with helical symmtery

  1. Measles Virus
  2. Beet Yellows Virus Particle
  3. Tobacco Mosaic Virus
  4. Vesicular Stomatitis Virus

COMPLEX

  • ATYPICAL viruses
  • Neither icosahedral nor helical

VIRUS

DESCRIPTION

Poxviridae

Oval/Brick-shaped

Bacteriophage T4 (E.coli)

Tailed phages

HIV-1

Conical capsids

Baculovirus

Rod-shaped capsids

Note: in HIV-1 and Baculovirus, virus genome is coated in highly basic protein (enveloped virions)

VIRAL GENOME

  • Stores the genetic information of the virus
  • REQUIREMENT:

Genome MUST contain the information coded in a form that can be RECOGNIZED and DECODED by the cell parasitized

CATEGORIES OF VIRAL GENOMES

  1. Double-stranded DNA (dsDNA)
  2. Single-stranded DNA (ssDNA)
  3. Double-stranded RNA (dsRNA)
  4. Single-stranded RNA (ssRNA)

CLASSIFICATIONS:

  1. According to NUCLEIC ACID CONFIGURATION:
  2. LINEAR
  3. CIRCULAR
  4. SEGMENTED
  5. According to SINGLE-STRANDED (ss) viral genomes:
  6. POSTIVE SENSE
  7. NEGATIVE SENSE
  8. AMBISENSE

DNA GENOMES

EXAMPLES

ss // linear

Parvovirus

ds // linear

Poxvirus

ss // circular

Phage Phi X174

ds // circular

Baculovirus

RNA GENOMES

EXAMPLES

ss // linear

Tobacco Mosaic Virus

ds // linear

Reovirus

ss // circular

Hepatitis delta virus

IMPORTANT!!

  • Most PLANT viruses have ssRNA genomes
  • Most FUNGAL viruses have dsRNA genomes
  • Most PROKARYOTIC viruses have dsDNA genomes

Reason: Diverse origin of viruses in different host types

GENOME SIZE

  • LARGE VIRUS GENOMES are composed of dsDNA
  • Largest RNA genomes: CORONAVIRUSES (33 kb ssRNA)
  • LARGEST VIRUS GENOME: Pandoravirus (2.8 Mb)

SEGMENTED GENOME

  • Genome DIVIDED INTO SEVERAL PARTS but enclosed into the same capsid
  • Example:

INFLUENZA VIRUS (ORTHOMYXOVIRIDAE)

8 RNA segments

Each segment codes for one protein

SEGMENT 4 codes for HEMAGGLUTININ

MULTIPARTITE GENOMES

  • Also have SEGMENTED GENOMES but are not contained in the same capsid, rather each segment is packaged into A SEPARATE VIRUS PARTICLE
  • Occurs in both RNA and DNA PLANT VIRUSES

ADVANTAGE OF MULTIPARTITE GENOMES

SOLVES THE PROBLEM OF BREAKAGES

DISADVANTAGE OF MULTIPARTITE GENOMES

THE HOST CELL MUST TAKE UP ALL VIRUS PARTICLES TO ESTABLISH A PRODUCTIVE INFECTION

IMPORTANT notes

SEGMENTED GENOMES:

  • More common in RNA VIRUSES than in DNA VIRUSES

MULTIPARTITE GENOMES:

  • More common among PLANT VIRUSES

VIRAL proteins

STRUCTURAL PROTEINS

  • Proteins that are COMPONENTS OF THE VIRIONS
  • FUNCTIONS:
  1. PROTECTION of the virus genome
  2. ATTACHMENT of the virion to the host cell (for many viruses)
  3. FUSION of the virion envelope to a cell membrane
  4. Provide STRUCTURAL SYMMETRY
  5. Determine ANTIGENIC CHARACTERISTICS of the virion

NON-STRUCTURAL PROTEINS

  • Proteins synthesized by the virus in an infected cell but are NOT VIRION COMPONENTS
  • FUNCTIONS:
  1. ENZYMES (protease, reverse transcriptase)
  2. TRANSCRIPTION FACTORS
  3. PRIMERS for NUCLEIC ACID REPLICATION
  4. INTERFERENCE with host immune response

NOMENCLATURE OF VIRAL PROTEINS

  1. STRUCTURAL PROTEINS: VP1, VP2, VP3…

note: VP = VIRAL PROTEIN

  1. NON-STRUCTURAL PROTEINS: NSP1, NSP2, NSP3
  2. STRUCTURAL CHARACTERISTIC:

G – GLYCOPROTEIN

P – PHOSPHOPROTEIN

  1. FUNCTION:

F – FUSION

P - POLYMERASE

RT – REVERSE TRANSCRIPTASE

ENVELOPE

  • LIPID-PROTEIN STRUCTURE that encloses the nucleocapsid
  • FLEXIBLE MEMBRANOUS STRUCTURE (thick lipid bilayer)
  • Derived from the HOST CELL MEMBRANE (Golgi, Nuclear Membrane, Cell Membrane)
  • Released by BUDDING of the particle through the membrane
  • Mostly found in ANIMAL VIRUSES
  • FEW in plant and bacterial viruses
  • Dissolved by ORGANIC SOLVENTS (e.g. ETHER)

ENVELOPE

EXAMPLES

Helical Nucleocapsid

Influenza Virus

Icosahedral Nucleocapsid

Herpesvirus

ENVELOPE PROTEINS

  1. GLYCOPROTEINS
  • TRANSMEMBRANE PROTEINS anchored to the membrane by a HYDROPHOBIC DOMAIN
  • Coded for by the VIRUS GENES
  • TYPES:
  1. EXTERNAL GLYCOPROTEINS

Referred to as SPIKES or PEPLOMERS

Project about 10 nm from the surface at 7-8 nm intervals

FUNCTIONS:

  1. Major Ag of enveloped viruses
  2. Provide contact with EXTERNAL ENVIRONMENT
  3. NEURAMINIDASE and HEMAGGLUTININ for influenza virus
  4. TRANSPORT CHANNEL PROTEINS

FUNCTIONS:

  1. Enable virus to alter the PERMEABILITY OF THE MEMBRANE
  2. Form PROTEIN-LINED CHANNEL through the envelope
  3. Contain MULTIPLE HYDROPHOBIC TRANSMEMBRANE DOMAINS
  4. Allows MODIFICATION OF THE INTERNAL ENVIRONMENT of the virion
  5. MATRIX (M) PROTEINS
  • INTERNAL virion proteins in the INNER SURFACE OF THE ENVELOPE (non-glycosylated)
  • LINKS the INTERNAL NUCLEOCAPSID to the ENVELOPE for stability
  • ABUNDANT because it encompasses 30% of the total weight of retroviruses

LOSS OF ENVELOPE LEADS TO LOSS OF VIRAL INFECTIVITY

REASONS:

  1. Lipid/lipoprotein may be required for attachment
  2. Loss of lipids may lead to loss of protection of nucleoproteins
  3. Solvents may extract lipids and denature proteins

VIRION SHAPE

EXAMPLES

Sphere

Influenza virus

Bullet

Rabies virus

Rod

Baculovirus

Thread

Ebola virus

With Internal Lipid Membrane

Iridovirus

VIRAL CARBOHYDRATES

  • Viral proteins have CARBOHYDRATE MOITIES found in the envelope
  • Attach the virus to the cell by INTERACTING WITH A RECEPTOR
  • Functions as an ANTIGEN

OCCLUSION BODIES

  • PROTEIN CRYSTALS produced by some viruses which provide ADDED PROTECTION outside the host

VIRION STRUCTURE

GENOMES

Icosahedral Naked

All genomes

Icosahedral Enveloped

Lacks ssDNA

Helical Naked

Lacks dsRNA

Helical Enveloped

ssRNA only