Viral Pathogenesis

Question 1

What are the stages of viral pathogenesis and infection?

Answer 1

• Animal vs Cell
• Entry into the host - Absorption
• Primary replication - Penetration
• Spread through the host - Uncoating
• Cell and tissue tropism - transcription
• Host immune responses - Translation
• Secondary replication - Replication
• Cell injury - Assembly
• Persistence - Release

Question 2

What is the Cytopathic effect?

Answer 2

• Can be seen in cell culture as:
  
  • Cytoskeletal disruption
  • Inclusions
  • Syncytia
  • Necrosis
  • Apoptosis
  • Lysis
• CPE caused by virus infection is not an unintended consequence of virus infection on the host cell
• Normally part of the virus infection/replication process

Question 3

What is an Inclusion body?

Answer 3

• Viral replication complexes in the nucleus or in the cytoplasm
  
  • Cells may stay intact, but form “inclusion bodies”
  • Inclusions are assembled in the nucleus or cytoplasm for synthesis of viral nucleic acids and assembly of virions

Question 4

What is a Syncytium?

Answer 4

• Fusion of cells into a single multinucleated cell

Question 5

Why study infection of cells?

Answer 5

• 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

Question 6

How do viruses cause disease?

Answer 6

• Virus 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

Question 7

What do viruses need for a successful infection?

Answer 7

• Enough virus to infect
• Susceptible and permissive cells
• Host defenses must be compromised or not effective

Question 8

How many virions are enough to cause infection?

Answer 8

• 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

Question 9

How do viruses survive outside a host?

Answer 9

• Some don’t
• Some stay in body fluids or fecal-oral
• Some survive the environment

Question 10

How can a Virus enter the host?

Answer 10

• Something needs to compromise the barrier for the virus to infect
• Virus get through the skin or mucosal membranes:
  
  • Skin - puncture
  • Eye - conjunctiva infected
    
    • blinking is a host defense
  • Alimentary tract - abrasions
  • Urogenital tract - abrasions
  • Mucosal Membranes of the Respiratory tract
    
    • does have host defenses such as mucus, cilia, macrophage

Question 11

Why is the skin a good barrier to viruses?

Answer 11

• low pH 5.5
• other microorganisms
• also desiccates the virus

Question 12

Which viruses enter through the skin?

Answer 12

• Poxviruses - mouse, cow, rabbit infect through breaks in the skin
• Papillomavirus - sexual contact
• Rhabdovirus - Animal bite
• Arboviruses - via the bite of an infected arthropod

Question 13

How do viruses enter through the respiratory tract?

Answer 13

• Barriers:
  
  • Mucus, cilia
  • Humoral and cellular immunity
• Viruses enter through droplets of saliva
• Environmental factors are important to stability of aerosolized virions
  
  • Temperature
  • humidity

Question 14

What viruses enter through the respiratory tract?

Answer 14

• Upper:
  
  • Arenaviruses, coronaviruses, respiratory syncytial virus (RSV), coxsackievirus
• :Lower
  
  • RSV, Influenza
• Entry to respiratory tract leading to systemic spread:
  
  • Hantavirus, poxvirus, arenaviruses

Question 15

How is the GIT susceptible to infection?

Answer 15

• Small intestine is a selectively permeable barrier
• There is direct contact with the outside
• Contains polarized epithelial cells
• Localized Infections:
  
  • stay in the epithelial cells next to the intestinal lumen
    
    • Coronavirus, rotaviruses
• Systemic infections:
  
  • spread within the host
    
    • enterovirus, reovirus, adenovirus

Question 16

How is the Urogenital Tract susceptible to viral infections

Answer 16

• Compromised epithelium can allow virus entry
• Localized:
  
  • papillomavirus
• Systemic:
  
  • Hepatitis B
  • herpes simplex virus
  • HIV

Question 17

How is the Conjuctiva susceptible to viral infections?

Answer 17

• Normally a localized infection of the eye
  
  • adenovirus
• Systemic infections can occur in the virus disseminates
  
  • Herpes simplex virus
  • enterovirus

Question 18

What are the types of infections?

Answer 18

• Acute
• Latent
• Progressive
• Chronic or persistent
• Failure to clear all evidence of infection

Question 19

What are the steps in a viral infection?

Answer 19

• Entry into host and primary virus replication
• Local or general spread in the host with secondary virus replication
• Shedding from host
• Clearance from the host

Question 20

What is the difference between localized and systemic infections?

Answer 20

• Localized:
  
  • virus stays close to the site of entry to replicate and spreads within the epithelium
  • virus is restricted to where it first infected
• Systemic:
  
  • Virus disseminates to infect other organs

Question 21

How do viruses spread within a host?

Answer 21

• Viruses pass through the basement membrane can get to blood vessels and lymphatic vessels
• Spreads to other tissues

Question 22

What is the Viremia Curve?

Answer 22

• Virus in the blood
• Infected animals 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

Question 23

What is Tropism?

Answer 23

• The ability of viruses to infect a specific tissue or type of cell
  
  • Viremia - blood
  • Hepatotropic - virus can replicate in the liver
  • Enteric - virus can replicate in GI
  • Neurotropic - virus can replicate in nerve tissues
    
    • Neurovirulent - causes disease in nervous tissue
    • Neuroinvasive - virus can enter the CNS