Viral Infection and Pathogenesis Flashcards
Primary types of transmission
Vertical: transmission from parent to offspring in utero
• Requires viremia, ability to cross placenta
• Most common during primary infection of mother
• Ex: congenital Rubella or CMV
Horizontal: transmission from one individual to another
• Most infections
List the 6 types of horizontal transmission
Respiratory Fecal-Oral Close contact Insect vector Animal vector Direct injection
Respiratory transmission
- Most common
- Also able to enter through conjunctiva
- Can be used by viruses not causing respiratory infections (measles)
- Spread via wet secretions that contaminate environmental surfaces
- Many viruses able to survive for days
- Also spread via sneezing = disperses fine particles into air
- Higher incidence in winter
Fecal Oral Transmission
- Common (though incidence is under-reported)
- Large amounts virus shed in feces
- Many = resistant to killing (survive long periods in environment)
- Heat resistant
- Protease resistant
- Can be alcohol-resistant
- Require higher bleach concentrations to kill
- Can be used by viruses that don’t cause diarrhea
- Most U.S. outbreaks due to contaminated food or water
- Ex: Rotavirus diarrhea, Poliovirus
Transmission by close contact
- Viruses = labile or shed in low amounts
- Most commonly by kissing or sex; can be via fomites (ex: HPV) or nursing
- Type used by many persistent viruses
Insect vectors
- > 400 viruses
- Mosquitos = most common; also via ticks
- Requires virus be able to replicate in both host and insect (broad host range)
Animal Vectors
- Bats very important
- Many considered “emergent” infections (Ebola virus, Lassa fever, Sin Nombre, SARS Coronavirus)
- Usually highly lethal because humans not natural host
- Requires virus replicates in animal vector
- Transmission via: bites, feces, contaminated urine, or butchering a carcass
- Ex: rabies
Transmission by Direct Injection
- Usually by contaminated needles
- Requires viremia in source host
- Common in IV drug users = needle sharing programs reduce transmission but do NOT eliminate due to cultural/social factors
- At risk = health care workers
Discuss viral entry into a host, including the most common entry sites
• Majority = via respiratory route
• 2nd most common = via GI tract
o Ex: polio virus or Coxsackie virus (both enter through GI but not cause GI symptoms)
• Next = via mucous membranes (genitalia or mouth) or close contact
By animal vectors:
o Direct injection through skin by mosquitoes
o Defecation of insect followed by scratching
o Inhalation of dried urine or feces (ex: Hantaviruses, Lassa fever virus)
Describe the processes involved in the spread of virus through the host in the two basic types of infections (local and disseminated).
Localized Infection.
o Virus remains localized at the site of entry
• Ex: Herpes simplex virus cold sores, Human papillomavirus warts
o Most respiratory viral pathogens (URT or LRT)
o Though virus remains localized, systemic symptoms can result (Influenza muscle aches and fever)
o Can spread in those who are immunocompromised
Disseminated infection.
o Virus spreads throughout the host following entry (usually via lymphatics)
• Must be able to penetrate basement membranes
o Multiple organs and tissues can be infected
Process:
• Localized replication in epithelial cells
• Virus spreads to lymphatics
• Small amounts of virus seed blood = Primary Viremia
• Transient and low titer
• Other cells (permissive cells), tissues, and organs are infected = Secondary Viremia
• Higher titer and more sustained
• Target tissues or organs now infected (liver, brain etc.)
• Development of specific symptoms
• Chance of developing symptoms increases with higher titer and duration of secondary viremia
Describe ways in which viruses directly damage cells and relate this to the causation of symptoms.
Host shut-off: infection → shutting down host gene expression
o Some viruses = severe host shut-off → direct killing of infected cells
o Other = selectively inhibit expression of specific host proteins
Inhibit host translation
o Major mechanism
Mechanisms:
• Altered phosphorylation of host initiation factors
• Proteolytic cleavage of host initiation factors
• Digestion of host mRNA
Inhibit host gene expression
o Block transcription of host genes by affecting DNA dependent RNA polymerase (Pol II)
o Interfere with splicing of host mRNA
o Interfere with transport of host mRNA to cytoplasm
Interfere with cell cycle
o Shutoff of host gene expression = stops the cell cycle
o DNA viruses cause cells to enter S phase = Stop it just before the cellular DNA actually replicates
o Entering S phase → increased expression of proteins and nucleoside substrates used in DNA replication
• The cells make more “goodies” for the virus to use
Apoptosis
o Viral infections triggers apoptosis
Good: defense mechanism
• Cell death before assembly stops infection
• All viruses encode functions to block apoptosis
• Anti-apoptotic functions have role in human cancer
Bad: some viruses activate apoptosis to help virus get out of cell and spread
Cell transformation
Define cytopathic effect and be able to list examples.
Viral infection resulting in changes in cell shape:
o Shrinkage of cell nucleus
o Cell rounding and detachment from plate (From disrupted tight junctions and actin cytoskeleton)
o Development of inclusion bodies (aggregations of viral material or virions) • Can be nuclear or cytoplasmic • Eosinophilic or basophilic Can be diagnostic • Ex: Negri bodies in rabies • Ex: Owl eye cells in Human CMV
o Cell-cell fusion (syncycium formation)
• Induced by enveloped viruses = infected cells fuse with adjacent uninfected cells → forms multi-nucleated cells
• Ex: HSV, Respiratory Syncytial Virus
• Allows for spreading in presence of neutralizing antibodes
Discuss the differences between acute and persistent infection.
Acute Infection o Host acquires virus o Host defenses respond o Host clears virus o Ex: common cold, influenza virus
Persistent Infection o Host acquires virus o Host defenses respond o Defenses not able to clear virus o Host infected for life or long period NOTE: high percentage of viral infections are subclinical
Describe the differences between latent and chronic infection. What is the most significant difference between the two patterns?
Both = types of persistent infections:
Chronic Infections
• The presence of isolatable infectious virus lasting longer than 6 months after initial infection
• Ex: Hepatitis B and C viruses
• Persons are infectious at all times (environmental source)
Latent Infections
• Virus cycles between periods where infectious virus is shed and the person is infectious and times when no infectious virus can be detected.
• Reactivation = virus shed asymptomatically
• Recrudescence = viral replication associated with symptoms
• Ex: Herpes, Adeno-, Papilloma, Papova-, and Parvoviruses
Note: HIV exhibits BOTH patterns
Acute vs. Chronic cancer viruses
Acute cancer viruses o Encode directly transforming genes o Short incubation period o Tumors are polyclonal o Several tumors can occur at the same time in a host o Ex: Kaposi’s Sarcoma (HHV8)
Chronic cancer viruses o Immortalize cells o Additional mutations required for cancer o Long incubation period o Tumors are monoclonal o Ex: HPV induced cervical cancer
