Transcript Sequential Steps in Viral Infection

Sequential Steps in Viral
Infection
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Entry
Spread
Shedding
Transmission
Propagation
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Three Problems Viruses
must solve:
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Reproduction
Spread
Evasion of Host
Defenses
Viral pathogenesis is
the result of viral
strategies designed to
overcome these
problems
Entry
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Skin/Mucous Membranes
Transcutaneous Injection
Urogenital Tract
Oropharynx and GI Tract
Respiratory Tract
Entry
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Skin/Mucous membranes
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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
Entry
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Skin/Mucous membranes
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Conjunctiva of the eye; a
specialized mucous
membrane
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Certain adenovirus
serotypes
Coxsackie virus A24
Enterovirus 70
Herpes Simplex Virus
Herpes Zoster
Virus infection can cause
severe conjuncvititis
Picornaviruses
(Acute Hemorrhagic Conjunctivitis)
Entry
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Transcutaneous Injection
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Arboviruses (Insect borne)
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Bite of infected animal (Rabies)
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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
Intramuscular innoculation with virus-contaminated saliva
Virus has pre-dilection for the limbic system; produces
personality changes
IV innoculation
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HIV
Hepatitis C
Entry
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Urogenital Tract (Sexually
Transmitted)
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Infects/replicates in epithelial
cells
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Puncture wound from needle
used to culture genital herpes
Herpes Simplex Virus-2 (herpes)
Papillomaviruses (warts, cervical
cancer)
Transmucosal infection
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Hepatitis B
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Access circulation via surface
capillaries that supply mucous
membranes
HIV
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textbook is not entirely correct;
HIV is probably “ferried” to
lymphoid organs to infect CD4+ Tcells by dendritic cells that reside
in the submucosa
Condyloma acuminatum (HPV-6)
DC-SIGN: A Conduit for Transfer
of HIV to Lymphoid Organs?
Geijtenbeek, T.B.H. et al, Cell 100: 594
Entry
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Oropharynx and
Gastointestinal Tract
ocalization of dise ase
astroen te ritis
o enteric illne ss
 system ic illness)
Repl icate in the
pharynx an d/or
gastroen te ric tract
Virus family
Represen tative e xample
YES
YES
YES
Astroviridae
C aliciviridae
C oronaviridae
YES
YES
YES
Rotaviridae
Parvoviridae
Adenoviridae
Astroviru se s
Norwalk virus
Transmissible
gastroen te ritis virus of
swine
Rotaviruses
C an ine parvoviru se s
Adenoviruses 40,41
YES
YES
YES
NO
YES
Picornaviridae
Picornaviridae
Picornaviridae
Picornaviridae
Adenoviridae
Polioviru s
C oxsackieviruses
En te roviru se s
Hepatitis A virus
Adenoviruses
ReoVirus
Entry
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Respiratory Tract
Hanta Virus
(Sin Nombre Virus)
Spread
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Local Spread
Dissemination
HIV in semen:
--Cell free virus vs
cell-associated virus
--consequences for
prophylactic treatment
Poliovirus Viremia
Viremia decreases with onset of
antibody response
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B
O
D
Y
VIREMA(LOG 10 TCD50PERML)
1
0
2
1
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ANTIBODY(TIERP0.25MLSERUM)
2
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0 2 4 6 81
01
2
D
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Virus Spread from Blood to Tissues
Some Paramyxovirus
(causes vasculitis)
(e.g. Mumps)
(“Trojan Horse”
e.g. HIV)
Shedding
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GI Tract
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Feces
 Epithelial Cells (Reovirus)
 Liver--->Bile---->Bile duct (Hepatitis A)
 Poliovirus
Respiratory Tract (Rhinovirus, Influenza)
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Aerosols, pharyngeal secretions
Skin
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Mucous Membranes (Oral/Genital fluids)
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Papillomavirus (Warts)
Pox viruses (smallpox)
HSV-1 (oral), HSV-2 (genital)
Epstein Barr Virus (mononucleosis--kissing disease in college kids)
Rabies (saliva)
HBV, HIV (semen)
Blood, Urine, Milk
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HBV, HIV, HCV, CMV (persistent viremia)
Enviromental Survival of Shed Virus
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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)
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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
1918 flu pandemic
killed 40 million people
in 5 months (~ same # killed
by HIV in the last 20 years)
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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
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CASEPR10POULATION
Acute Infections
1
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1
9
0
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1
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9
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9
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1
9
3
0
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% with Antibody
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Cases per 100 population
Transmission/Propagation
0
1
9
4
0
Transmission/Propagation
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Persistent Infections
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Can persist in small populations
HIV, HBV, VZV
Control and Eradication
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Effective vaccines can eradicate viral
infections that result in acute infections
in relatively short periods of time
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Smallpox, Polio(?)
Persistent infections will take
generations to disappear, even with
effective vaccines