1. Sequential Steps in Viral Infection
Entry
Spread
Shedding
Transmission
Propagation
Three Problems Viruses must solve:
Reproduction
Spread
Evasion of Host Defenses
Viral pathogenesis is the result of viral strategies designed to overcome these problems

2. Entry Skin/Mucous Membranes Transcutaneous Injection Urogenital Tract
Oropharynx and GI Tract
Respiratory Tract

4. Entry Skin/Mucous membranes Invasion of intact skin unlikely
Stratum corneum is keratinized, no live cells
Break in skin allows viral access to
specific underlying cells
Herpes Simplex Virus and pox viruses can replicate in germinal cells in epidermis and fibroblasts and macrophages in the dermis
Papillomaviruses (causes cervical warts and cancer) infect germinal cells of the epidermis but complete life cycle only in the more superficial stratum granulosum

5. (Acute Hemorrhagic Conjunctivitis)
Entry
Skin/Mucous membranes
Conjunctiva of the eye; a specialized mucous membrane
Certain adenovirus serotypes
Coxsackie virus A24
Enterovirus 70
Herpes Simplex Virus
Herpes Zoster
Virus infection can cause severe conjuncvititis
Picornaviruses
(Acute Hemorrhagic Conjunctivitis)

6. Entry Transcutaneous Injection Arboviruses (Insect borne)
Virus life cycle must alternate between insect vector and vertebrate host (e.g. West Nile Virus, Dengue Virus)
Virus is injected when the insect takes a blood meal
Symptomalogy can differ widely: non-symptomatic to fatal encephalitis for West Nile, and slight febrile illness to fatal hemorrhagic fever for dengue
Bite of infected animal (Rabies)
Intramuscular innoculation with virus-contaminated saliva
Virus has pre-dilection for the limbic system; produces personality changes
IV innoculation
HIV
Hepatitis C

7. Entry Urogenital Tract (Sexually Transmitted)
Puncture wound from needle
used to culture genital herpes
Urogenital Tract (Sexually Transmitted)
Infects/replicates in epithelial cells
Herpes Simplex Virus-2 (herpes)
Papillomaviruses (warts, cervical cancer)
Transmucosal infection
Hepatitis B
Access circulation via surface capillaries that supply mucous membranes
HIV
textbook is not entirely correct; HIV is probably “ferried” to lymphoid organs to infect CD4+ T-cells by dendritic cells that reside in the submucosa
Condyloma acuminatum (HPV-6)

8. DC-SIGN: A Conduit for Transfer of HIV to Lymphoid Organs?
Geijtenbeek, T.B.H. et al, Cell 100: 594

9. Entry
Oropharynx and Gastointestinal Tract
ReoVirus

10. Entry
Respiratory Tract
Hanta Virus
(Sin Nombre Virus)

11. Spread HIV in semen: Local Spread Dissemination --Cell free virus vs
cell-associated virus
--consequences for
prophylactic treatment

12. Poliovirus Viremia
Viremia decreases with onset of
antibody response

13. Virus Spread from Blood to Tissues
Some Paramyxovirus
(causes vasculitis)
(e.g. Mumps)
(“Trojan Horse”
e.g. HIV)

14. Shedding GI Tract Feces Epithelial Cells (Reovirus)
Liver--->Bile---->Bile duct (Hepatitis A)
Poliovirus
Respiratory Tract (Rhinovirus, Influenza)
Aerosols, pharyngeal secretions
Skin
Papillomavirus (Warts)
Pox viruses (smallpox)
Mucous Membranes (Oral/Genital fluids)
HSV-1 (oral), HSV-2 (genital)
Epstein Barr Virus (mononucleosis--kissing disease in college kids)
Rabies (saliva)
HBV, HIV (semen)
Blood, Urine, Milk
HBV, HIV, HCV, CMV (persistent viremia)

15. Enviromental Survival of Shed Virus
Transmission depends
Amount of shedding
Duration of Shedding
Survival time in environment
HIV not infectious after drying
Poliovirus sensitive to low humidity
Decrease transmission during Winter
Transmission all year in tropical climates
GI Environment (acid inactivates most viruses)
Hep A, B, C, D, E all replicate in liver and are secreted in bile but only Hep. A and E are transmitted by fecal-oral route

16. 1918 flu pandemic
killed 40 million people
in 5 months (~ same # killed
by HIV in the last 20 years)

17. Transmission/Propagation
Acute Infections
Requires minimal population threshold
Transmissibility, Ro>1
E.g. Measles will eventually disappear if isolated population <500,000
Ab prevalence may provide an indicator of transmissibility; age and population-specific incidence
Cases per 100 population
% with Antibody

18. Transmission/Propagation
Persistent Infections
Can persist in small populations
HIV, HBV, VZV

19. Control and Eradication
Effective vaccines can eradicate viral infections that result in acute infections in relatively short periods of time
Smallpox, Polio(?)
Persistent infections will take generations to disappear, even with effective vaccines