1. Lecture 21: Dissemination, Virulence, and Epidemiology
Text: Flint et al, Chapter 14

2. General points To establish a successful infection, viruses must
Find a way to enter the host
Find a way to get through the host defences
Move through the host
Find the right cell types to infect
To spread infection, viruses must
Find a way for new viral progeny to exit infected cells and host
Find a way to survive outside of host

3. Initiation of infection
Sufficient virus must be available
High concentrations.
A sneeze droplet contains up to 100 million Rhinovirus particles.
Similar amount of Hepatitis B in 1ml of infected blood.
High survivability in harsh exterior environments
Dilution
pH changes
Dissecation
Cells at site of infection must be
Accessible
Susceptible
Permissive
Local host defenses must be
Absent or
Initially ineffective

4. Viral Entry: respiratory tract
Common route for viruses
Aerosolized droplets
Coughing, sneezing
Large droplets deposited in nose
Smaller ones further down the Resp. tract
Must overcome
Clearance by mucus
Inactivation by antibodies
Destruction by macrophages.

5. Viral Entry: respiratory tract
Fig. 14.2

6. Viral Entry: alimentary tract
Common route of entry and dispersal
Virus must be resistant to
Stomach acids
Bile bases (detergents)
Destroys most enveloped viruses.
Somehow many Coronaviruses survive
Proteases
Many viruses, e.g. Reovirus particles, are actually activated by intestinal proteases.

7. Viral Entry: into M cells

8. Viral Entry: into M cells
Most of gut is lined with columnar villous epithelial cells.
Apical sides are densely packed with microvilli
“Brush border” coated with glycoproteins, glycolipids and mucus
Difficult to penetrate
M cells: lymphoid cells scattered throughout gut
Thin, absorptive,
Normally transmit antigens to underlying lymphtocytes via transcytosis
Some viruses infect only M cells
e.g. Rotavirus, Coronavirus transmissible gastroenteritis
Lyse M cells, cause mucosal inflammation, diarrhea
Others transcytose through M cells into underlying basal membranes and extracellular space. e.g. Reoviruses
From there, can go to
Lymphatic system
Circulatory system
Rest of host

9. Viral Entry: through Urogenical tract
Physical barriers: mucus, low pH (vagina only)
Viral entry via tears and abrasions due to normal sexual activity
Viruses can infect epithelium and cause local lesions, e.g. some papillomaviruses
Others infect underlying tissues, and invariably spread and persist
Neurons, e.g. herpesviruses
Lymphoid tissue, e.g. HIV

10. Viral Entry: through eyes
Physical barriers: tears, mucus, proteases
Entry via abrasions, poor sanitation
Most infections are localized: conjunctivitis
Herpesvirus Type I infections can spread to neurons and become persistent

11. Viral entry: through skin
Presents formidable physical barriers
Entry via breaks in skin
Abrasions, e.g. papillomaviruses: usually local
Insect bites, e.g. West Nile
Animal bites, e.g. rabies
Behavior: needles, tattoos, body piercing
Fig. 14.4

12. Evasion of host defenses
Active and passive mechanisms
Active: knock out immune mechanisms
Passive:
Overwhelming numbers
Infect immunonaive organs, e.g. Rabies

13. Kinetics of viral replication and immune response
Fig. 14.5

14. Viral Spread After replication at site of entry, virus can
Remain localized
e.g. rhinovirus in respiratory epithelium
Spread to other tissues
e.g. polio from gut epithelium to neural tissues
Disseminated infection – virus spread to other tissues
Systemic infection – virus spread to many organs
Shedding – release of virus from infected cells/tissues

15. Polarized viral spread
Direction of virus particle release determines how virus will spread
Release at apical membranes: localized or limited infection
e.g. Influenza
Release at basal membranes: disseminated/systemic infections
e.g. VSV
Vessicular Somatitis Virus
Fig. 14.6

16. Hematogenous Spread Spread through the blood.
Virus replicates at site of entry, exits infected cells
Enters bloodstream – primary viremia
Infects other organs, replicates, exits into bloodstream – secondary viremia
Replicates yet again in other organs, exits passed on.
Fig. 14.7

17. Neural spread
Many viruses spread from primary site of infection by entering local nerve endings
Typically, such viruses enter from a nerve ending or axon
Replicate in the cell body
Directionally exit the neuron: retrograde vs. antiretrograde
Routes of entry can be
Neural: poliovirus, herpesviruses
Olfactory: herpesviruses, coronaviruses
Hematogenous: polio, coxackievirus, mumps, measles, CMV

18. Neural spread Box 14.3. anterograde vs retrograde spread
Fig pathways of neural spread
Fig : olfactory spread

19. Organ invasion
From viremia, subsequent replication requires invasion of new cells and tissues
Three main types of blood vessel-tissue interfaces provide routes for invasion
Capillary: very tight basement membrane
Venule: contains pores through basement membrane
Sinusiod: very leaky, macrophages form part of blood-tissue junction
Fig

20. Viral entry routes into the liver
Fig

21. Virus shedding and transmission
Shedding: release of infectious viruses from infected host
Respiratory secretions. e.g rhinoviruses, influenza viruses
Aerosolization – sneezing, coughing
Contamination of fomites by nasal secretions
Saliva. e.g. mumps, cytomegalovirus, rbies
Contamination of fomites – spitting, coughing, wiping hands
Kissing, grooming (animals)
Animal bites
Feces, e.g. enteric and hepatic viruses
Poor sanitation, food contamination, sexual exchange
Blood, e.g. sindbis viruses (West Nile), Denge virus, hepatitis, HIV
Transmission by biting insects, during sex, childbirth, exposure to contaminated blood
Urine (viruea)
Hantaviruses, arenaviruses
Semen
HIV, some herpesviruses, hepatitis B
Milk
Mouse Mammary tumor virus, Mumps, CMV
Skin lesions
Poxviruses, HSV, varicella zoster, papillomaviruses, Ebola virus

22. Epidemiology
Definition: The study of the occurrence of a disease in a population.
Includes:
Mechanisms of viral transmission
Risk factors for infection,
Population size required for virus transmission
Geography
Season
Means of control

23. Mechanisms of viral transmission
Aerosol
Food and water
Fomites
Body secretions
Sexual activity
Birth
Transfusion/transplant
Zoonoses (animals, insects)

24. Factors that promote transmission
Virus stability
Virus in aerosols and secretions
Asymptomatic shedding
Ineffective immune response

25. Geography and Season
Vector ecology; School year; Home heating season

26. Critical population size
Risk factors
Critical population size
Age
health
immunity
occupation
travel
lifestyle
children
sexual activity
Numbers of seronegative susceptible individuals

27. Means of control Quarantine – SARS
Vector elimination – mosquito control and West Nile
Immunization – MMR, DPT, etc…
Antivirals – triple therapy and AIDS