Attachment to host cells
Lecture 10
BSCI437
Chapter 5, pp. 127 – 151.
Overview
 Viruses must adhere to cells
 Attach to specific receptors
o Exceptions:
 Viruses of Fungi: no extracellular phase (see lect. 7)
 Viruses of plants: entry via mechanical damage (lecture 27)
 Some require a second molecule for further refinement: co-receptor
Finding the right partner
 Susceptible cell: has receptor that virus can recognize
 Permissive cell: has internal machinery/components that virus requires
Cell surface architectures (Fig. 5.1)
 Vertebrate bodies covered with epithelial cells
 Two topological surfaces (polar distribution)
o Apical: presented to outside
o Basal: presented to inside.
 Viral infections are initiated at exposed apical surfaces
 Transcytosis: passage of a virus (or any other molecule) through one cell so that
it may access another. Used by eg. Polio and HIV-1.
The plasma membrane (fig. 5.4)
 Phospholipids/glycolipid bilayer (membrane)
 Membrane proteins
 Phospholipids are ampipathic
o Polar headgroups face into aqueous environment
o Non-polar tails face into the bilayer
 Different associations of lipids create microdomains
o Lipid rafts: dense. Rich in cholesterol and saturated fatty acids.
o Microdomains important for entry and exit of some viruses
o e.g. HIV-1, Ebola.
Cell membrane proteins (Figs. 5.5, 5.6)
Integral
 Embedded into cell membrane
 Many contain membrane spanning domains
o -helical, typically 3.7 nm long, hydrophobic
 Others anchored via carbohydrate chains (fig. 5.6)
o Tend to be on outer side of cell
 Some anchored by myristoyl- or farnesyl- chains.
o Tend to be on inner cytoplasmic face of cell
Indirectly anchored.
 Interact with integral membrane proteins and/or sugars
Interaction of viruses with cell receptors
General principles:
Any surface molecule can serve as a receptor for virus attachment.
Some viruses attach to more than 1 receptor
Different viruses can attach to the same receptor
Expression of surface molecule determines who and what gets infected
 Host range: host must express the surface molecule in order for infection to
occur.
 Tissue Tropism: tissue must express the surface molecule in order for infection
to occur. E.g. HIV-1 can only infect cells that express the CD4 surface protein:
T-helper cells, macrophages, glial cells.
 Experimental strategies for identification and isolation of cellular genes encoding
viral receptors (Fig. 5.7)
Single receptor binding (Figures 5.8 and 5.9)
Picornavirus family has adapted to recognize a wide variety of surface molecules
Focus on Icam-1 / Human rhinovirus interaction (Fig. 5.8).
Numerous different molecules recognize and bind to different regions of
Icam-1 (Fig. 5.9A)
HRV recognizes specific loops on the distal D1 domain of Icam-1 (Fig. 5.9B)
Icam-1 fits into a canyon of HRV that is formed between VP1, VP2 and VP3
(Fig 5.9C).
Focus on PVR/poliovirus interaction (Fig. 5.9D).
Poliovirus capsid evolved so that domain 1 of PVR fits into the canyon at the
interface between the structural units. 60 PVR binding sites/viral particle.
Co-receptors
Many viruses require binding to more than 1 receptor for efficient infection.
 Example: The primary receptor for HIV-1 is the CD4 surface protein of T-cells.
 However, the CCR5 surface protein is also required by HIV-1 for efficient entry.
 People with certain CCR5 mutants do not get AIDS
How virions attach to receptors
Generally, Animal viruses have multiple receptor binding sites.
Various mechanisms
Hooks
Conformational changes: pH, proteolytic
“unzippers”: vSNARES
Nonenveloped viruses
Tend to attach via surface features, e.g. canyons and loops.
Canyons: Picornavirus binding to Icam-1 example, Fig. 5.12A
Loops: Adenovirus binding to Car receptor, Fig. 5.13, top.
Enveloped viruses
Tend to attach to receptors via viral membrane glycoproteins
Example: attachment of HIV-1 SU with cell receptor CD4 (Fig 5.11C)