Lecture 21: Dissemination, Virulence, and Epidemiology
Text: Flint et al, Chapter 14.
BSCI437
General points
 To establish a successful infection, viruses must
o Find a way to enter the host
o Find a way to get through the host defences
o Move through the host
o Find the right cell types to infect
 To spread infection, viruses must
o Find a way for new viral progeny to exit infected cells and host
o Find a way to survive outside of host
Initiation of infection
 Sufficient virus must be available
o High concentrations.
 A sneeze droplet contains up to 100 million Rhinovirus particles.
Similar amount of Hepatitis B in 1l of infected blood.
o High survivability in harsh exterior environments
 Dilution
 pH changes
 Dissecation
 Cells at site of infection must be
1. Accessible
2. Susceptible
3. Permissive
 Local host defenses must be
o Absent or
o Initially ineffective
Viral Entry: respiratory tract (Fig. 14.2)
 Common route for viruses
 Aerosolized droplets
o Coughing, sneezing
o Large droplets deposited in nose
o Smaller ones further down the Resp. tract
 Must overcome
o Clearance by mucus
o Inactivation by antibodies
o Destruction by macrophages.
Viral Entry: alimentary tract
 Common route of entry and dispersal
 Virus must be resistant to
o Stomach acids
o Bile bases (detergents)
 Destroys most enveloped viruses.
 Somehow many coronaviruses survive
o Proteases
 Many viruses, e.g. reovirus particles, are actually activated by
intestinal proteases.
Viral Entry: through M cells (Fig. 14.3)
 Most of gut is lined with columnar villous epithelial cells.
o Apical sides are densely packed with microvilli
o “Brush border” coated with glycoproteins, glycolipids and mucus
o Difficult to penetrate
 M cells: lymphoid cells scattered throughout gut
o Thin, absorptive,
o Normally transmit antigens to underlying lymphtocytes via transcytosis
 Some viruses infect only M cells
o e.g. Rotavirus, Coronavirus transmissible gastroenteritis
o Lyse M cells, cause mucosal inflammation, diarrhea
o Others transcytose through M cells into underlying basal membranes and
extracellular space. e.g. Reoviruses
o From there, can go to
 Lymphatic system
 Circulatory system
 Rest of host
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
o Neurons, e.g. herpesviruses
o Lymphoid tissue, e.g. HIV
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
Viral entry: through skin (Fig. 14.4)
 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
Evaision of host defenses
 Active and passive mechanisms
 Active: knock out immune mechanisms
 Passive: overwhelming numbers
 Infect immunonaive organs, e.g. Rabies
Kinetics of viral replication and immune response
See Fig. 14.5.
Viral Spread
 After replication at site of entry, virus can
o Remain localized
 e.g. rhinovirus in respiratory epithelium
o 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
Polarized viral spread (Fig. 14.6)
 Direction of virus particle release determines how virus will spread
 Release at apical membranes: localized or limited infection
o e.g. Influenza
 Release at basal membranes: disseminated/systemic infections
o e.g. VSV
Hematogenous Spread (Fig. 14.7)
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.
Neural spread (see Figs. 14.11, Box 14.3, Fig. 14.12)
 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 (box 14.3)
 Routes of entry can be
o Neural: poliovirus, herpesviruses
o Olfactory: herpesviruses, coronaviruses
o Hematogenous: polio, coxackievirus, mumps, measles, CMV
Organ invasion (Fig. 14.13)
 From viremia, subsequent replication requires invasion of new cells and tissues

Three main types of blood vessel-tissue interfaces provide routes for invasion
1. Capillary: very tight basement membrane
2. Venule: contains pores through basement membrane
3. Sinusiod: very leaky, macrophages form part of blood-tissue junction.
Virus shedding and transmission
Shedding: release of infectious viruses from infected host
 Respiratory secretions. e.g rhinoviruses, influenza viruses
o Aerosolization – sneezing, coughing
o Contamination of fomites by nasal secretions
 Saliva. E.g. mumps, cytomegalovirus, rbies
o Aerosolization – sneezing, coughing
o Contamination of fomites – spitting, coughing, wiping hands
o Kissing, grooming (animals)
o Animal bites
 Feces, e.g. enteric and hepatic viruses
o Poor sanitation, food contamination, sexual exchange
 Blood, e.g. sindbis viruses (West Nile), Denge virus, hepatitis, HIV
o Transmission by biting insects, during sex, childbirth, exposure to
contaminated blood
 Urine (viruea)
o Hantaviruses, arenaviruses
 Semen
o HIV, some herpesviruses, hepatitis B
 Milk
o Mouse Mammary tumor virus, Mumps, CMV
 Skin lesions
o Poxviruses, HSV, varicella zoster, papillomaviruses, Ebola virus
Epidemiology
Definition: the study of the occurrence of a disease in a population.
Includes:
1. Mechanisms of viral transmission
2. Risk factors for infection,
3. Population size required for virus transmission
4. Geography
5. Season
6. Means of control
Mechanisms of viral transmission
 Aerosol
 Food and water
 Fomites
 Body secretions
 Sexual activity
 Birth


Transfusion/transplant
Zoonoses (animals, insects)
Factors that promote transmission
 Virus stability
 Virus in aerosols and secretions
 Asymptomatic shedding
 Ineffective immune response
Geography and Season
 Vector ecology
 School year
 Home heating season
Risk factors
 Age, health, immunity, occupation, travel, lifestyle, children, sexual activity
Critical population size
 Numbers of seronegative susceptible individuals
Means of control
 Quarantine – SARS
 Vector elimination – mosquito control and West Nile
 Immunization – MMR, DPT, etc…
 Antivirals – triple therapy and AIDS