Sequential Steps in Viral Infection Entry Spread Shedding

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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

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Entry

• Skin/Mucous Membranes
• Transcutaneous Injection
• Urogenital Tract
• Oropharynx and GI Tract
• Respiratory Tract

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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

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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)
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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

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

• Oropharynx and Gastointestinal Tract

ReoVirus
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Entry

• Respiratory Tract

Hanta Virus (Sin Nombre Virus)
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Spread

• Local Spread
• Dissemination

HIV in semen --Cell free virus vs
cell-associated virus --consequences for
prophylactic treatment
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Poliovirus Viremia
Viremia decreases with onset of antibody response
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Virus Spread from Blood to Tissues
Some Paramyxovirus (causes vasculitis)
(e.g. Mumps)
(Trojan Horse e.g. HIV)
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Shedding

• GI Tract
• Feces
• Epithelial Cells (Reovirus)
• Liver---gtBile----gtBile 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)

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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

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1918 flu pandemic killed 40 million people in 5
months ( same killed by HIV in the last 20
years)
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Transmission/Propagation

• Acute Infections
• Requires minimal population threshold
• Transmissibility, Rogt1
• E.g. Measles will eventually disappear if
  isolated population lt500,000
• Ab prevalence may provide an indicator of
  transmissibility age and population-specific
  incidence

Cases per 100 population
with Antibody
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Transmission/Propagation

• Persistent Infections
• Can persist in small populations
• HIV, HBV, VZV

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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