Viral Pathogenesis Flashcards
Viral pathogenesis:
Stages
Animal → cell
entry into the host → absorption
Primary replication → penetration
Spread through the host → uncoating
Cell and tissue tropism → transcription
Host immune response → translation
Secondary replication → replication
Cell injury → assembly
Persistence → release
Viruses in cell culture
Cells / virus are grown in
Tissue culture flasks or plates
Viruses in cell culture:
Cytopathic Effect
CPE: cytopathic effect
can be seen in cell culture as:
inclusions, cytoskeletal disruption, syncytia, necrosis, apoptosis, lysis
Viruses in cell culture:
Inclusion bodies
- Viral replication complexes in the nucleus or in the cytoplasm
- Cells may stain intact, but form “inclusion bodies”
- Inclusions are assembled in the nucleus or cytoplasm for synthesis of viral nucleic acids and assembly of virions
Viruses in cell culture:
Syncytium
- Fusion of cells into a single multinucleated cells
Experimental systems we use to study the virus
diagnostic tool
obtain a pure virus culture
understand basic biological process related to pathogenesis
Develop and test antivirals and vaccines
Replace the use of live animals
Viral pathogenesis:
How do viruses cause disease
enters the host
Primary replication of the virus
Spread in the host
Fate of the virus infection
cleared, persistent, acute, benign
Transmission to another host
Viral Pathogenesis:
Successful infection
- must have:
- enough virus to infect
- susceptible and permissive cells
- Host defenses must be compromised or not effective
Viral pathogenesis:
Enough Virions to infect
- This varies a lot with the host and the virus
- health of host - immune compromised
- Age of host - young or old
- Behavior of host - outside a lot for vector-borne viruses
- Virulence of the virus
Viral pathogenesis:
How does a virus survive outside the host
- some don’t, they go from host to host
- Others stay in body fluids or fecal-oral
- Some are able to survive in the environment
Virus must enter the host
- Something needs to compromise the barrier for the virus to infect
- Virus get through the skin or mucosal membranes
- The skin is a good barrier - can be punctured by bite, puncture
- Eye - conjunctiva can get infected - host defense can be blinking
- Alimentary tract - abrasions during digestion
- Urogenital tract - abrasions can allow the virus to enter
- Mucosal membranes are easy to infect
- Respiratory Tract - does have host defenses such as mucus, cilia, macrophages
Virus must enter the host:
Skin
- Normally a good barrier unless it is compromised
- Good barrier due to:
- low pH (5.5)
- other microorganisms
- Also desiccates the virus
- Poxviruses:
- mouse, cow, rabbit infect through breaks in the skin
- Sexual contact:
- papillomavirus
- Animal bites:
- rhabdovirus
- Arboviruses:
- go through the skin via the bite of an infected arthropod
- flaviviruses, alphaviruses, bunyaviruses, togaviruses, reoviruses, poxvirus
- go through the skin via the bite of an infected arthropod
Virus must enter the host:
Respiratory tract
- Barriers:
- mucus, cilia, humoral and cellular immunity
- Viruses enter the respiratory tract through droplets or saliva
- Environmental factors are also important to stability of aerosolized virions
- temperature
- humidity
- Upper tract:
- arenaviruses, coronaviruses, respiratory syncytial virus, coxsackievirus
- Lower tract:
- RSV, Influenza
- Entry to respiratory tract leading to systemic spread
- hantavirus, poxviruses, arenaviruses
Virus must enter the host:
Gastrointestinal tract
- small intestine is a selectively permeable barrier
- There is direct contact with the outside
- Contains polarized epithelial cells
Virus must enter the host:
GI tract:
Localized infection
stay in the epithelial cells next to the intestinal lumen
coronavirus, rotaviruses
Viral replication and spread in the host
- An infected animal will have this general curve:
- passive viremia:
- burst of virus upon inoculation
- Primary viremia
- virus replicates
- Secondary viremia:
- virus multiplies in other organs so the viremia is amplified
- passive viremia:
