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Lecture 21: Dissemination, Virulence, and Epidemiology

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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


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