The common tasks faced by
(almost) all viruses.
1.
2.
3.
4.
5.
6.
7.
8.
Cell attachment – binding to
a cell surface receptor.
Entry via receptor—
mediated endocytosis.
Release of genome into
cytoplasm via membrane
fusion.
Transcription of viral
mRNAs and of new viral
genomes (RNA viruses)
Viral protein synthesis and
assembly of provirus.
Maturation of viral particle.
Release of virus from cell.
Evasion of host defense and
transmission to new host.
Overview
• Viruses must adhere to cells
• Attach to specific receptors
– 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)
– Apical: presented to outside
– 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.
Major types of epithelia
Simple Squamous: thin
cells, e.g. blood vessels
Simple Columnar: thick,
typically mucus
secreting, eg. GI tract,
cervix
Transitional epithelia:
several layers with cells
of different shapes.
Expandable, e.g. urinary
bladder
Stratified Squamous:
nonkeratinized,
resistant to abrasion.
Epidermal layer of skin,
mouth, vagina.
The plasma membrane (fig. 5.4)
• Phospholipids/glycolipid bilayer
(membrane)
• Membrane proteins
• Phospholipids are ampipathic
– Polar headgroups face into aqueous
environment
– Non-polar tails face into the bilayer
• Different associations of lipids create
microdomains
– Lipid rafts: dense. Rich in cholesterol and
saturated fatty acids.
– Microdomains important for entry and exit
of some viruses
• e.g. HIV-1, Ebola.
Cell membrane proteins
Integral
• Embedded into cell membrane (fig.
5.6)
• Many contain membrane spanning
domains
a-helical, typically 3.7 nm long,
hydrophobic
Cell membrane proteins
Integral
• Embedded into cell
membrane
• Anchored via
carbohydrate
chains (fig. 5.6)
• Anchored by
myristoyl- or
farnesyl- chains.
– 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 virus binding and
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 (Fig. 5.9A).
Icam-1 / Human
rhinovirus interaction
Numerous different
molecules recognize and
bind to different regions
of Icam-1 (Fig. 5.9A).
Icam-1 / Human
rhinovirus interaction
• 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).
PVR/poliovirus
interaction (Fig. 5.9D).
• Poliovirus capsid evolved a “canyon”
• Allows 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 Tcells.
• 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 virus
attachment
• 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 virus
attachment
• Tend to attach to receptors via
viral membrane glycoproteins
Example: attachment of
HIV-1 SU with cell
receptor CD4 (Fig 5.11)
CD4
Right: ribbon diagram
Left: space filling
HIV-1 SU
The CD4 – SU
interaction
SU
CD4
SU
CD4