[1] Adsorption

• In adsorption, virus particles attach to molecule on host cell surface

  • There is Virion - Host receptor interaction
• Viruses always binds to a specific receptor on the host cell
• Host receptors may be:

  1. Proteins
  2. Lipids
  3. Carbohydrates
• The first virus receptor identified was the receptor for bacteriophage lambda

  • Receptors are involved in the uptake of maltose by host cell
  • Example of a transporter
• Functions of the receptors for the cell:

  1. Signaling molecules
  2. Adhesion molecules
  3. Transporters
• Because receptors have specific functions in the cell, we cannot genetically engineer cells to not have receptors
• If host lacks receptors for a virus, it is not a permissible host for the virus
• Viruses that do not have receptors:

  1. Fungal
  2. Yeast
  3. Plant
• Fungal and yeast viruses do not have an extracellular phase
• Bridging of hyphae

  Anastomosis
• Plant viruses are able to enter via cell wall damage

  • Facilitated by arthropod vectors feeding on leaves
• Most receptors are integral proteins
• Most receptors are involved in cellular adhesion
• Influenza A is an enveloped virus

  • Has several glycoproteins described as spikes
  • Requires sialic acid to enter the cell
• Receptor protein positioned perpendicularly

  Hemagglutinin
• Glycoprotein that binds to sialic acid

  Hemagglutinin
• Match Influenza with host sialic acid:

  1. Avian - Alpha 2, 3 linked sialic acids
  2. Human - Alpha 2, 6 linked sialic acids
  3. Porcine trachea - Alpha 2, 3 and Alpha 2,6 linked sialic acids
• Process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype

  Antigenic shift
• Melting pot for the emergence of new flu viruses

  Pigs
• Virus and Host Receptor Interactions:

  1. One virus can recognize multiple receptors
  2. Different viruses can bind to the same receptor
  3. Some viruses require more than one receptor
  4. Some bind to soluble proteins
• One virus can recognize multiple receptors:

  1. Herpes simplex virus type 1
  2. Has several receptors
• Different viruses can bind to the same receptor

  1. Ex. Adenovirus and Coxsackie virus
• Some viruses require more than one receptor

  1. Involves a co-receptor
  2. Ex. HIV CD4 as the main receptor, but also binds to a co-receptor
• In HIV, binding to CD4 is followed by an engagement of CCR5, resulting in membrane fusion
• Some bind to soluble proteins:

  1. Ex. Zika virus binds to receptor and soluble extracellular/membrane proteins
  2. Binding to protein is required
• Virus receptor for HIV

  gp120
• gp120 recognizes cd4 on specific cells

  • Helper T cells and macrophages express cd4
• HIV co-receptor: CCR5

  • Binding to cd4 is followed by CCR5
  • Both bind to gp120
  • gp120 is needed for membrane fusion
• What leads to membrane fusion in HIV?

  Binding to co-receptor
• Individuals homozygous for the 32-CCR5 allele are resistant to HIV infection
• HIV changes in tropism as disease progresses to AIDS

  • Initially, co-receptor is CCR5, which binds to beta chemokine
  • Through random mutation, co-receptor is expressed by CCR4 instead, which binds to alpha chemokine

  
• Therapy for AIDS focuses on chemokine receptor antagonists

  • CCR5 - maraviroc, vicriviroc, aplaviroc
• What stabilizes virus-receptor interaction?

  Each virion has multiple sites that can bind to receptors (high avidity)
• Initially, attachment is reversible

  • Over time, stabilized by several noncovalent interactions
• Methods to verify if cell surface molecule is virus receptor:

  1. Add normal ligand to growing cell (blocks)
  2. Monoclonal antibody against cell surface molecule (blocks)
  3. Soluble derivatives of cell surface molecule (blocks)
  4. Expression of gene encoding molecules into virus-resistant cells (makes cells susceptible)
• Mice and rats cannot get infected with SARS-COV2 because:

  They do not have any receptors
• Providing the receptor protein is sufficient to make cells susceptible to infection
• Virus involved in colds

  Rhinovirus C
• The cysteine in CDHR3-Cys529 protects humans from Rhinovirus C