Lecture 16-17: Virus Structure and Function

What Is a Virus?

  • Noncellular particle that must infect a host to replicate.

  • Usually hijacks the host cellular machinery to make more viruses.

  • Depends on host metabolism (obligate intracellular parasites).

    • Energy, materials, enzymes all come from the host.

  • Virion: virus particle and consists of the nucleic acid and protein coat.

  • Always has a small genome.

    • DNA or RNA, single- or double-stranded.

  • Always has a protective capsid (protein coat).

Viruses are Everywhere

  • Viruses are everywhere: in all environments and places.

  • Different viruses infect every group of organisms.

  • Estimate of 103210^{32} viruses on earth.

  • Each virus infects a specific group of hosts (host range).

  • Viral genomes contain only information for taking over host cell.

    • “Early” genes.

    • Information for making viral proteins.

      • Capsid, genome replication proteins.

Virus Structure and Classification

  • The viral capsid packages the genome and delivers it into the host cell (capsid + genome = nucleocapsid).

  • The viral capsid is composed of repeated protein subunits.

  • This maximizes the capacity while minimizing the required number of genes.

  • Different viruses make different capsid forms.

    • These can be divided into two main types:

      • Symmetrical and asymmetrical

  • Viruses can be classified by their shape and structure.

  • Viruses can be classified by genome composition or replication mechanism.

    • This classification is more useful and important.

Icosahedral Viruses

  • Polyhedral with 20 identical triangular faces.

  • Have a structure that exhibits rotational symmetry.

Icosahedral Viruses with Envelopes

  • In some icosahedral viruses, the capsid is enclosed in an envelope, formed from the host cell’s membrane.

  • Between the envelope and capsid, you’ll find tegument proteins.

Filamentous Viruses

  • The capsid consists of a long tube of protein, with the genome coiled inside.

  • Vary in length, depending on genome size.

  • Include bacteriophages as well as animal and plant viruses.

  • Helically symmetrical

  • Capsid monomers form a tube around the genome.

Asymmetrical Viruses

  • These have complex multipart structures.

  • T4 bacteriophages

    • Have icosahedral “head” and helical “neck.”

Pox Viruses

  • The genome is surrounded by several layers.

    • Core envelope studded with spike proteins.

    • Outer membrane.

Viral Life Cycles

  1. Attach to host cell

  2. Get viral genome into host cell

  3. Replicate genome

  4. Make viral proteins

  5. Assemble capsids

  6. Release progeny viruses from host cell

Viral Genomes

  • DNA or RNA

  • Single- or double-stranded (ss or ds)

  • Linear or circular

  • Include genes encoding viral proteins

    • Capsid

    • Envelope proteins (if need be)

    • Any polymerase not found in host cell

Viral Genomes and Classification (Baltimore Classification)

  • Viruses classified by their nucleic acids and replication mechanisms.

  • Group I. dsDNA (e.g. herpes, smallpox)

  • Group II. ssDNA (e.g. Parvovirus, Geminiviruses)

  • Group III. dsRNA (e.g. Rotavirus, Reoviruses)

  • Group IV. (+)ssRNA (e.g. COVID, HepC, cold viruses)

  • Group V. (-)ssRNA (e.g. Flu, rabies, Ebola)

  • Group VI. RNA retroviruses (use reverse transcriptase to make DNA from RNA: e.g. HIV)

  • Group VII. DNA pararetroviruses (e.g. HepB)

Baltimore Classification of Viruses - Detailed

  • Class I: dsDNA

    • Replication: dsDNA

    • Transcription: mRNA

    • Translation: Protein

  • Class II: ssDNA

    • Replication: ssDNA -> dsDNA

    • Transcription: mRNA

    • Translation: Protein

  • Class III: dsRNA

    • Replication: dsRNA -> positive sense ssRNA

    • Transcription: mRNA

    • Translation: Protein

  • Class IV: (+)ssRNA (positive sense)

    • Replication: (+)ssRNA -> (-)ssRNA -> (+)ssRNA

    • Translation: Protein

  • Class V: (-)ssRNA (negative sense)

    • Replication: (-)ssRNA -> (+)ssRNA

    • Transcription: mRNA

    • Translation: Protein

  • Class VI: RNA Retroviruses

    • Replication: ssRNA(+) -> dsDNA

    • Transcription: mRNA

    • Translation: Protein

  • Class VII: DNA Pararetroviruses

    • Replication: dsDNA -> ssRNA -> dsDNA

    • Transcription: mRNA

    • Translation: Protein

RNA Viruses - Classification Criteria

  • Nucleic acid: dsRNA, (+)ssRNA, (-)ssRNA

  • Symmetry of capsid: Icosahedral, Helical

  • Naked or enveloped

  • Genome architecture

  • Baltimore class: III, IV, V, VI

  • Family name: Reo, Birna, Calici, Picorna, Flavi, Toga, Retro, Corona, Filo, Rhabdo, Bunya, Orthomyxo, Paramyxo, Arena

The Flu (Influenza) - A Detailed Example

  • Humans have been dealing with Influenza for a long time.

  • Influenza (The Flu) is caused by a –ssRNA virus.

  • Key components:

    • Neuraminidase (NA)

    • Ion channel (M2)

    • Envelope: Lipid bilayer

    • Matrix protein (M1)

    • Hemagglutinin (HA)

    • Segmented (-) strand RNA genome

    • Cap and RNA polymerase (PB1, PB2, PA)

    • Nuclear export protein (NEP)

    • Nucleocapsid protein (NP)

  • (-) strand RNA segments undergo mRNA synthesis and translation.

  • Splicing occurs, resulting in different proteins (e.g., M1, M2).

  • Proteins produced: PB2, PB1, PA, HA, NP, NA, M1, M2, NEP.

  • RNA-dependent RNA polymerase is involved.

The Flu - H1N1 and Reassortment

  • Eight RNA segments from a given strain.

  • H1N1

    • PB2, PA

    • NP, M, NS

    • H1, N1

  • Sporadic infection of humans with swine reassortant viruses.

  • Triple-reassortant swine H1N1 2009 human outbreak.

    • H1 from classical swine.

    • N1, M from avian-like swine.

  • Avian virus components: PB2, PB1, PA.

  • Seasonal H3N2.

The Flu - Sialic Acid and Receptor Binding

  • Avian sialic acid: α-2,3 to galactose.

  • Human sialic acid: α-2,6 to galactose.

  • Swine sialic acid: α-2,3 or α-2,6 to galactose.

  • Sialic acid binds to receptor proteins on the cell membrane.