Virus Disease in Populations and Individual Animals

1
Chapter 3

• Virus Disease in Populations and Individual
  Animals

2
Routes of Transport

• Some viruses can survive for long periods of time
  outside the host but the ultimate source of viral
  pathogen is an active infection in other host

3
Viruses with Human Reservoirs

• Majority of human viruses are maintained in the
  human population human vector
• rhinovirus, papillomavirus, HIV etc
• spread by human behavior and symptoms
• cold lead to coughing and sneezing virus spread
  in aerosol droplets
• HSV requires direct contact but related VZV is
  aerosolized
• HIV is spread in body fluids sex, needles,
  transfusion

4
Viruses with Vertebrate Animal Reservoirs

• Zoonoses transmit a disease from a vertebrate
  to humans
• Rabies spread by animals to humans but usually
  no human to animal or to human so we are dead end
  for virus animals can be infectious for a long
  time before symptoms are seen transmitted by a
  bite
• Some viral zoonosis require an arthropod for
  human spread can pass virus between host 1 and
  host 2 or can actually replicate in the
  arthropod when arthropod bites, it will inject a
  large inoculum of virus

5
Viruses in Populations

• If an effective immune response is made against a
  virus and the virus has infected a large portion
  of a population then the virus dies out as
  there are no more host susceptible
• see this happen in isolated areas

6
Viral Spread

• Level of colds decline until a new wave of
  visitors start to come into Antarctica in the
  spring

7
Lasting Immunity

• Generation of lasting immunity can help control
  or even eradicate the virus
• from an active infection or vaccination
• Use vaccination of wild raccoons to decrease the
  spread of rabies in domestic animals and
  ultimately humans
• Some viruses will continue to evade eradication
• HSV by latency and reactivation
• HIV by tight association with the immune system
• Flu because of the large number of strains that
  out there
• Major constraint on vaccination programs is the
  economics requires to create vaccine and
  then more to get everyone the immunization

8
Kochs Postulates

• Pathogen must be isolated from every patient with
  symptom of the disease
• Pathogen must be cultivated in pure form
• Pathogen must cause disease in a suitable host

9
Models of Viral Pathogenesis

• Humans cant be used for ethical reasons
• Tuskegee syphilis studies Black men where left
  on placebos to see the long term effect of the
  disease when they knew they had a drug that would
  work
• gave rise to the Informed Consent explain all
  the possible outcomes
• Need accurate animal models
• get reliable data by manipulating variable
  factors
• useful information from very simple experimental
  procedures
• Basic methods are observation, dissection and
  measurement of virus

10
Model Pitfalls

• Keep in mind that animals can only approximate
  the human disease
• still important because the course of the disease
  and recovery can function on controlled
  variations of the infection an physiology of the
  host
• Plants have too long of a generation time
• Animals are expensive to obtain and keep
• Infection must be the same in all subjects which
  is not the way it is in real world
• Must use the same type of animal sex, age, type
  etc., not the way it truly is

11
Mouse Model of Poxvirus

• Infect in the footpad and look for the virus in
  various organs, antibody titers and degree of the
  rash
• Usually, primary infection is in the lungs by
  breathing in an aerosol of the virus

12
Mouse Reovirus

• Reovirus has genome of 10 specific fragments of
  dsRNA that each encode for one protein of the
  most outer structure of the virus
• If 2 cells are in one cell, can get random
  reassortment that parts of each parent in the
  new virus attribute a phenotype to a specific
  gene
• Can use model to study aspects of pathogenesis
  what is controlled by what gene?
• different viruses will infect different tissues
  and spread to different tissues
• Doesnt help in understanding of viral disease
  and spread in humans but has helped in knowing
  that the route of infection can aid in describing
  the pathogenesis

13
Mouse Models

• Use of newborn mice demonstrates a different
  viral disease than using adult mice that have
  been engineered to have severe combined
  immunodefiecency syndrome (SCID, boy in the
  bubble syndrome)
• newborn mice have a limited immune system that is
  still better than no immune response at all

14
Rabies

• Very old virus evidence in the Middle Ages
• Has a very long incubation period that plays a
  role in the mechanism of spread
• Can vaccinate the victim of the bite and they
  will be able to mount an immune response before
  the infection is able to over

15
Rabies Replication

• Inoculate virus at the site of the bite, limited
  replication at this site
• Virus must enter the sensory nerve ending to
  replicate in the neuron
• Spread passively to the nerve cell body in dorsal
  root ganglion (DRG) high level of viral
  replication
• Moves to cerebral cortex and cerebellum high
  level of viral replication
• Distinct behavioral changes
• Virus moves out of the CNS to sensory neurons and
  salivary glands replicates and is available to
  spread to another by bites

16
Prevent the spread by severing the sciatic
nerve
17
Immunofluorescent Labeled Rabies Infected Tissue
18
HSV Latency

• HSV-1 facial lesions or cold sores
• HSV-2 genital lesions
• Difference in the 2 is the mucosal infection
• Establish latent infections in humans and
  reactivation plays a role in viral spread
• Several animal models but still a limitatiom as
  only reflects partial course of disease in
  natural host - humans

19
Mouse Model HSV-1

• Eye or footpad infection localized infection
  and spread to CNS and then the brain may have
  some deaths
• Survivors have latent infection in sensory nerve
  gangli
• no infectious virus in nerve tissue
• explant nerve tissue and look for virus on a
  monolayer of feeder cells, will eventually see
  virus need to have this second step to see the
  effects of the virus
• Model used to study the establishment and
  maintenance of latent infection cant easily
  study reactivation

20
Mouse Model
21
Rabbit Model HSV-1

• Infect in the eye, localized infection and
  recovery
• Virus ends up in the trigeminal ganglia (TG),
  viral DNA or virus or both can be recovered from
  the tissue
• Spontaneous shedding of virus, useful for
  reactivation studies
• Induced reactivation using iontophoresis or
  epinephrine
• More expensive to buy and harder to keep than mice

22
Guinea Pig Model HSV-2

• Used for many human infections
• HSV-2 is usually used in a vaginal inoculation
  local infection and establishment of latency
• Virus and viral DNA can be found in nerves
  innervating the vaginal area
• HSV-2 reactivates spontaneously in the GP

23
Kingdom Hopping?

• Very little evidence to indicate viruses can move
  between kingdoms
• plants to animals
• animals to bacteria
• bacteria to plants
• It could potentially happen in future due to
  stress on environments