Transcript Virology - Lecture #1

Introduction to Virology
Tony Mazzulli, MD, FRCPC
September 21, 2009
Virology
Objectives
1.
To understand the characteristics/properties of
viruses which make them unique microbial
pathogens
2.
To examine the structure and composition of
viruses
3.
To understand the classification of viruses
4.
To understand the replication strategies of
viruses
Virus Properties
• Virus is defined as a nucleoprotein complex
which infects cells and uses their metabolic
processes to replicate
• Smallest known infective agents
• Metabolically inert - no metabolic activity
outside host cell; must enter host cell to
replicate
• Most are highly species specific
Virus versus Virion
• Virus is a broad general term for any aspect of the
infectious agent and includes:
• the infectious or inactivated virus particle
• viral nucleic acid and protein in the infected cell
• Virion is the physical particle in the extra-cellular
phase which is able to spread to new host cells;
complete intact virus particle
Characteristics of Infectious Microorganisms
Property
Bacteria
Viruses
Fungi
Protozoa
Size (nm)
100 -10,000
30 - 300
4,000 - 40,000
4,000 - 40,000
Nuclear structure
Prokaryotes
----
Eukaryotes
Eukaryotes
Obligate
intracellular
No
Yes
No
No
Nucleic acids
DNA/RNA
Haploid
DNA or RNA
DNA/RNA
DNA/RNA
Yes
No
Yes
Yes
Culture on
Artificial media
Relative Sizes of Microorganisms
Limits of
resolution
Light
microscope
0.2 m
50,000-V
electron microscope
0.003 m
Unaided
human eye
40 m
Microscopic
protozoa & fungi
4 - 40 m
Classes of
organisms
0.001
Viruses
0.03 - 0.3 m
0.01
0.1
Size (m)
Bacteria
0.1 - 10 m
1
10
100
Virus Structure
• consist of a core of nucleic acid surrounded
by a protein coat +/- envelope
• components of virus particle include:
i) nucleic acid - DNA or RNA
- single - or double - stranded
- intact / fragmented;
linear / circular
- encodes very few proteins
Virus Structure
ii) proteins:
a) structural - capsid made of capsomeres
- serve as antigens which elicit an
immune response
b) enzymes - differ from host cell
- targets of antiviral therapy
iii) envelope - found in some viruses;
- lipoprotein envelope containing
viral and host cell components
- destroyed by lipid solvents
Virus Structure
Virus particles exhibit 3 types of capsid symmetry:
1. helical - tubular: most helical viruses possess an
outer envelope (eg. measles)
2. icosahedral - isometric or cubic; may (eg. herpes)
or may not (eg. adenovirus) possess an outer
envelope
3. complex - does not conform to either of above (eg.
vaccinia)
Adenovirus
Herpesviridae
Influenza Virus
Smallpox Virus
Virus Classification
• Historically based on:
– Host preference: Plant, insect, animal, human
– Target organ: respiratory, hepatic, enteric, etc.
– Vector: arboviruses
• Overlapping, inconsistent
• Currently based on molecular biology of
genome and biophysical structure
Virus Classification
• Viruses with similar structural, genomic &
replication properties are grouped into families
(suffix: viridae) e.g. Herpesviridae
• Families subdivided into genera (suffix: virus) e.g.
Herpes simplex virus, Cytomegalovirus, Varicella
zoster virus
• Subtypes based on nucleotide sequence and
antigenic reactivities e.g. Herpes simplex virus
type 1, Herpes simplex virus type 2
Virus Classification
Viruses
Nucleic acid:
Envelope:
Symmetry:
DNA
Yes
Cubic
(Icosahedral)
RNA
No
Helical
(Cylindrical)
Classification of Some Common Viruses
Family
Picornaviridae
Type of
Nucleic Acid
ss (+) RNA
Viruses
Enteroviruses,
polio, hep. A
Caliciviridae
Norwalk virus
ss (+) RNA
Togaviridae
Rubella
ss (+) RNA
Rhabodoviridae
Rabies
ss (+) RNA
Paramyxoviridae Parainfluenza,
ss (-) RNA
RSV, measles,
mumps
Orthomyxoviridae Influenza
ss (-) RNA
Retroviridae
HIV 1,2, HTL I,II
ss (+) RNA
Hepadnaviridae
Hepatitis B
ds DNA
Parvoviridae
Parovirus B - 19
ss (+) or (-) DNA
Adenoviridae
Adenovirus
ds DNA
Herpesviridae
HSV, CMV, EBV,
VZV, HHV6
ds DNA
I = icosahedral, H = helical
Envelope
No
Capsid
Symmetry
I
No
Yes
Yes
Yes
I
I
H
H
Yes
Yes
Yes
No
No
H
I
Unknown
I
I
Yes
I
Virus Classification (Common)
DNA
RNA
Hepatitis B
Human Papilloma Virus
Parvovirus B19
Adenovirus
Herpesviridae
Polyomaviruses
Influenza
RSV
Parainfluenza
Hepatitis A, C, D, E
Enteroviruses
Encephalitis viruses
Measles, Mumps, Rubella
Norwalk, Rotavirus
Virtually all others
Viral Replication
i)
ii)
iii)
iv)
v)
vi)
vii)
adsorption (attachment)
entry
uncoating
transcription
synthesis of virus components
assembly
release
Viral Replication
i) Adsorption (attachment):
• random collision
• interaction between specific proteins on viral surface
and specific receptors on target cell membrane
(tropism)
• not all cells carrying a receptor for a particular virus
can be productively infected by that virus
Viral Replication
i) Adsorption (attachment):
– some viruses may use more than one host
cell receptor (e.g. HIV)
– able to infect a limited spectrum of cell
types (host range)
– most neutralizing antibodies are specific for
virion attachment proteins
Viral Replication
ii) Entry (penetration):
• 2 mechanisms - endocytosis
- fusion of virus envelope with
cell membrane
iii) Uncoating:
• release of viral genome
• cell enzymes (lysosomes) strip off the virus
protein coat
• virion can no longer be detected; known as the
“eclipse period”
Viral Replication
iv) Transcription/Translation/Synthesis:
a)
•
•
•
•
DNA viruses:
replicate their DNA in host cell nucleus mediated by
viral enzymes
synthesize capsid and other proteins in cytoplasm
using host cell enzymes
new viral proteins move to nucleus where they
combine with new DNA to form new viruses
Exception - Poxviruses synthesize their parts in host
cell’s cytoplasm
Viral Replication
iv) Transcription/Translation/Synthesis:
b) RNA viruses:
–“+” sense RNA acts as mRNA - viral
proteins are made immediately in
cytoplasm mediated by viral enzymes
–“-” sense RNA (e.g. influenza) - lst makes a
“+” sense RNA copy via viral enzyme
Viral Replication
iv) Transcription/Translation/Synthesis:
• Retroviridae (e.g. HIV)
• Contain enzyme “Reverse transcriptase”
• “+” sense Viral RNA  cDNA 
integrated into host cell chromosone
• mRNA (for viral proteins) and progeny
virion RNA are synthesized from
integrated viral DNA by host cell enzymes
(RNA polymerases)
Viral Replication
v) Synthesis:
• Protein synthesis - 2 types
• structural
• non-structural (enzymes for replication)
• Nucleic acid synthesis
• new virus genome
• most often by a virus - coded polymerase or
replicase; with some DNA viruses a cell
enzyme carries this out
Viral Replication
vi) Assembly:
• may take place in cell nucleus, cytoplasm or
(with most enveloped viruses) at the plasma
membrane
vii) Release:
• sudden rupture of cell
• gradual extrusion (budding) of enveloped
viruses through the cell membrane
• may occur together with assembly
Enveloped Virus Entry via Fusion
Non-enveloped Virus Entry via Endocytosis
Outcome of Viral Infections
Adsorption (attachment)
Entry
Replication
Latency Transformation
Release
Cell Fusion
Outcome of Viral Infections
Virus-host cell interaction may result in:
1. Cell death (lytic) - due to cytopathic effect of
virus
2. Cell transformation - cell converted to
malignant or cancerous cell
3. Latent infection (occult) - persistent infection
in quiescent state which may reactive
anytime to produce disease; continuous or
intermittent shedding
4. Cell fusion to form multinucleated cells
Persistent Viral Infections
3 types of persistent viral infection (some
overlap):
1. Chronic carrier - eg. Hepatitis B; results in
chronic illness
2. Latent infection - eg. Herpesviridae; result in
symptomatic or asymptomatic shedding
3. Slow virus infections - due to prolonged
incubation period (eg. Measles virus and SSPE)
Host - Organism Relationship
• Interaction between host and organism affecting
the development and outcome of an infection
includes:
– Host’s primary physical barriers
– Host’s immunologic ability to control and eliminate
the invading organisms
– Organism’s ability to evade destruction/virulence
– Ability of organism to spread in the body
Virulence of Viruses & Evasion of the
Immune Response
• Poorly understood processes:
– Antigenic variation
– Some viruses encode receptors for various mediators of
immunity (eg. IL1 & TNF) thus blocking their ability to
interact with receptors on their intended targets
– Some viruses (eg. HIV) reduce expression of class I MHC
proteins, thus reducing ability of cytotoxic T cells to kill the
virus-infected cells
– Direct cell-to-cell propagation
– Attenuated viruses (eg. Vaccine strains)
Definitions
• Exposure: contact with a potentially infectious
agent
• Infection: persistence on or within another living
organism
• Disease: end product (damage) resulting from an
infectious process
• Incubation: time from infection to development of
symptoms / disease
Virus: Incubation Times
Hours to 1-2 days:
• Respiratory viruses
• GI viruses
1 to 3 weeks:
• Measles/Mumps/Rubella
• VZV, HSV
• Chlamydia
• Enteroviruses, Polio
• WNV
Weeks to months:
• Hepatitis viruses
• HIV
• EBV
• Rabies
Months to years:
• Prions
Routes of Transmission
• Horizontal transmission:
– Direct contract (secretions, blood etc.)
– Respiratory (aerosol)
– Contaminated inanimate objects
– Insect vector (mosquitoes, ticks, etc.)
– Zoonoses
• Vertical transmission:
– Mother to fetus [Transplacental
(Congenital), Perinatally]
Viruses - Transmission
• Can occur - with or without disease
- during asymptomatic
shedding
- during incubation period
• Transmission results in primary infection 
disease; reactivation results in secondary
disease
Viruses - Epidemiology
•
•
•
•
•
•
•
•
mode of transmission
age
gender
ethnic background / country of origin
travel history
occupation
season
underlying medical condition(s)
Thank you for your attention!