1. Introduction to Virology
Tony Mazzulli, MD, FRCPC
September 21, 2009

2. 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

3. 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

4. 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

5. Characteristics of Infectious Microorganisms

6. Relative Sizes of Microorganisms
Light
microscope
0.2 m
Limits of
resolution
50,000-V
electron microscope
0.003 m
Unaided
human eye
40 m
Microscopic
protozoa & fungi m
Classes of
organisms
Bacteria m
Viruses m
0.001
0.01
0.1 10
100 1
Size (m)

8. 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

9. 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

10. Virus Structure Virus particles exhibit 3 types of capsid symmetry:
helical - tubular: most helical viruses possess an outer envelope (eg. measles)
icosahedral - isometric or cubic; may (eg. herpes) or may not (eg. adenovirus) possess an outer envelope
complex - does not conform to either of above (eg. vaccinia)

12. Adenovirus

13. Herpesviridae

14. Influenza Virus

15. Smallpox Virus

16. Virus Classification Historically based on: Overlapping, inconsistent
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

17. 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

18. Virus Classification Viruses Nucleic acid: DNA RNA Envelope: Yes No
Symmetry: Cubic Helical
(Icosahedral) (Cylindrical)

19. Classification of Some Common Viruses
I = icosahedral, H = helical

20. Virus Classification (Common)

21. Viral Replication i) adsorption (attachment) ii) entry iii) uncoating
iv) transcription
v) synthesis of virus components
vi) assembly
vii) release

22. 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

23. 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

24. 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”

25. 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

26. 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

27. 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)

28. 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

29. 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

30. Enveloped Virus Entry via Fusion

31. Non-enveloped Virus Entry via Endocytosis

32. Outcome of Viral Infections
Adsorption (attachment)
Entry
Replication Latency Transformation
Release
Cell Fusion

33. Outcome of Viral Infections
Virus-host cell interaction may result in:
Cell death (lytic) - due to cytopathic effect of virus
Cell transformation - cell converted to malignant or cancerous cell
Latent infection (occult) - persistent infection in quiescent state which may reactive anytime to produce disease; continuous or intermittent shedding
Cell fusion to form multinucleated cells

34. Persistent Viral Infections
3 types of persistent viral infection (some overlap):
Chronic carrier - eg. Hepatitis B; results in chronic illness
Latent infection - eg. Herpesviridae; result in symptomatic or asymptomatic shedding
Slow virus infections - due to prolonged incubation period (eg. Measles virus and SSPE)

35. 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

36. 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)

37. 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

38. 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

41. 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]

42. 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

43. Viruses - Epidemiology
mode of transmission
age
gender
ethnic background / country of origin
travel history
occupation
season
underlying medical condition(s)

44. Thank you for your attention!