(V) 25: Viral Pathogenesis Flashcards
Why is skin not a good host?
B/c it is mostly DEAD SKIN
- viruses need something alive for ribosomes to work
Inapparent infections
able to transmit even though host does not know they are infected
- no major symptoms but immune system is activated
Flaviridae
ex. West Nile Virus
- INAPPARENT infection
(+) ssRNA - ready to go WITH ENVELOPE
- spread my mosquitoes
- 1st North American case 1999 in NYC
- almost caused cancellation of US Open Tennis Tourney –> instead sprayed insecticide
- CDC was mystified b/c they couldn’t test for a virus they didn’t have in their collection
80% of infected ppl do NOT have symptoms
transmitted IN blood –> could be passed through transfusion (blood donation)
How did West Nile Virus make it to North America?
Likely originated in Israel (closest match to virus in NYC)
discovered through using physical measurement - SEQUENCING
- make primer sequences/oligonucleotides from small bit of viral genome then amplify w/ PCR
First virus known to cause disease in humans
Yellow Fever Virus
- Reed Commission: US soldiers becoming sick in Cuba
Dr. Lazear inoculated Dr. Caroll with an infected mosquito
- inject virus in human –> virus can kill human –> virus can induce pathogenesis
Viral pathogenesis
To produce a disease
TWO ARMS
1. effects of viral replication on HOST
2. effects of HOST RESPONSE on virus and host
Viral pathogenesis steps
- virus enters cell and loses its shell
- virus exposes nucleic acid
- virus uses host ribosome machinery to make viral proteins
- assembly
- leave and infect next cell
need a susceptible AND permissive cell
also need the “right #” of virus particles - no set #
Fenner experiment
unfortunate pathogenesis of mousepox
mousepox was injected into the footpad
- host response = swelling at sit of inoculation
- after viremia: host response = replication in skin = rash (viremia)
- invasion of skin and multiplication in susceptible + permissive cells
- multiplication in lymph node
- primary viremia
- multiplication + necrosis in spleen and liver
- secondary viremia
- swelling of foot - primary lesion
- early rash: Papules
- severe rash: Ulceration
Viremia
presence of virions in the blood
Primary viremia
progeny virions released in blood after initial replication at site of entry
Secondary viremia
delayed appearance of virions in the blood
Viral entry points
- conjunctiva (via outer surface of eyes)
following are lined w/ mucosal cells:
- respiratory
- alimentary
- urogenital
viruses enter via mucosal linings of respirator, alimentary and urogenital tracts - lots of susceptible + permissive cells
Skin
Epidermis (outer layer) = DEAD CELLS
- violates “host requirement”
skin can be broken by insects and viruses may enter via blood (ex. WNV)
- virus gains access to vascularized DERMIS
virions will be INACTIVATED by:
- acidic (pH= 5.5) on skim surface
- anti-viral peptides
- dryness
How are virions inactivated on the skin?
- ACIDIC skin surface (pH = 5.5)
- anti-viral PEPTIDES
- DRYNESS
Respiratory tract viruses
- lots of surface area for viruses to find susceptible + permissive cells
- viruses often enter in form of AEROSOLIZED droplets or through SALIVA CONTACT
- mucous layer production = mucus removes intruders
Ex. Rhinovirus (common cold), influenza virus
Alimentary tract viruses
- can “COME DOWN” with food
- must survive HARSH acidic environments
- can get absorbed by small intestine
upper alimentary tract: acidic pH, proteases, bile detergents (Ex. Reoviruses - viruses that cause gastroenteritis)
lower alimentary tract (anus): virus does not have to withstand harsh environment of upper alimentary tract (Ex. HIV - entry via anal intercourse)
Reoviruses
Non-enveloped, ONION-like genome, dsRNA
onion-like genome = has to go through many layers
- layers protect genome from harsh environment of upper alimentary tract
Lower alimentary tract
Anus
less acidic
Ex. HIV
Urogenital tract
Mucus and pH protection (especially low pH in vagina)
Abrasions during sexual activity will create tears and allow viral entry (ex. losing low pH of vagina)
Ex. Retrovirus (HIV) and HPV
Conjunctival entry
- eyes are covered by layers of cell (conjunctiva)
- blinking is a defense mechanisms
- certain types of ADENOVIRUSES can infect conjunctiva
- cornea is partially covered by conjunctiva
Virus Shedding
Release of virions form infected individual
Transmission - viral population will survive if many infections in series occur in a host population
Methods of Virus Shedding
- aerosol secretions: coughing, talking, sneezing
- feces
- blood
- milk (breastfeeding)
- urine, semen
- skin lesion (ex. herpes infected skin lesions transmits virus during close contact - think wrestling)
Virus Shedding and Envelopes
Enveloped viruses are more fragile = easier to KILL
- mostly AEROSOL transmission
- sensitive to low pH
Non-enveloped: withstand a LOT including LOW pH
- mostly transmitted in RESPIRATORY, FECAL-ORAL route
- also transmitted via FOMITES (objects contaminated by virus)
Modes of transmission
- iatrogenic
- nosocomial
- vertical
- germline
- horizontal
Iatrogenic transmission
Health care WORKER infects a patient
Nosocomial transmission
Patient infected while in a HOSPITAL
- could be due to fomites
Vertical transmission
PARENT TO OFFSPRING
- through childbirth or breastfeeding
Germline transmission
genomic transfer
- through chromosomal segregation
Horizontal transmission
NONE of the others
- transmission btwn two same or different species
MOST COMMON MODE OF TRANSMISSION
Picornaviridae Hep A
(+) RNA
entry: alimentary tract
- spreads to liver causing JAUNDICE
- virus incubates for 30 days
- in later 90s, every February, 10-40% of residents in Puglia, Italy develop Hep A
- residents eat RAW shellfish that live in contaminated water/sewage on NYE
- humans that are Hep A positive poop in water - virus shedding in FECES into shellfish habitat
