An outline of virus replication and viral pathogenesis

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Chapter 2

• An outline of virus replication and viral
  pathogenesis

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Viral Replication

• Viruses must replicate in the cell- produce
  changes in the cell to get viral genes replicated
  and the proteins expressed
• use part of the cells equipment to replicate the
  viral nucleic acids, express viral genes, all of
  the cells protein machinery and energy stores
• Viruses are smaller than ribosomes

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Key Words

• Productive infection 1 virus infects a cell and
  usually generates many more viruses, can be a
  factors of 10 higher
• Burst size actual number of infectious virus
  produced
• cell becomes a viral factory, interaction between
  virus and cell is dependent on virus and cell
  type
• Lysogeny co-existence of virus and cell genome
  together with changes in protein composition of
  cell, found in bacteria
• Transformation is this same process in plants and
  animals altered growth properties and may have
  some or many characteristics of cancer cells
• may be instances that the co-existence doesnt
  cause a change in the cell

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Viral Size

• E. coli is 5 ?m 1/500 of eukaryotic cell
• Virus is 25 200 nm (0.025 0.200 ?m)

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More Key Words

• Recrudescence reactivation of the virus from a
  sleeping state
• HSV can establish a latent infection in
  differentiated sensory neurons no viral
  proteins expressed
• Viruses in plants can result in stable
  association also called Mosaicism more than 1
  distinct genotype interdispersed in a tissue
  details not well understood

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Basic Viral Replication

• Virus specifically interacts with host cell
  surface (receptor) and viral genome is introduced
  into the cell
• Viral genes expressed using host cell processes
• Viral proteins modify host cell and allow viral
  genome to replicate using host and viral enzymes
• New viral coat proteins assemble into capsids and
  viral genomes are included
• Virus is released where it can infect new cells
  and repeat the process

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Pathogenesis of Viral Infection

• Pathogenesis is sum total of genetic features a
  virus encodes that allows its efficient spread
  between individuals host and the population of
  hosts
• Not all viral infections result in measurable
  disease symptoms
• Unapparent or asymptomatic infection can result
  from many factors
• influenced by hosts genetic makeup
• some are results of viral gene function
• some are random (stochastic)

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Stages of Infection

• Initial infection
• Viral replication at site of entry
• Multiplication
• Spread to favored tissues spread of infection
  to others
• Incubation period time between initial
  infection and observation of clinical symptoms
  variable length of time
• Host response will lead to adaptive immunity

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Initial Stages of Infection

• Source of virus is the reservoir
• Organism that spreads the disease is a vector
• An organism can be both reservoir and vector
• dynamic virus must be replicating constantly
• not dynamic algal viruses in water but no algae
  in Antarctica, but the virus is there so there
  must be some replication somewhere

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Viral Entry

• Viruses must enter via receptors on an assessable
  surface, wet surface
• Many different areas that the virus may enter

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Incubation of Virus in Host

• Must replicate at site of infection takes time
• only a limited amount of virus introduced
• innate immunity responses occur immediately upon
  infection interferon response
• Early stage may last from days to years
  dependent on the virus
• Most viral infections may be cleared before we
  get to this stage may be contained at the site
  of infection

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Spread of Virus in Host

• After entry, must move to target tissue or organs
  may often but not necessarily contribute to
  disease symptoms
• Viral spread is common thru circulatory system
  viremia
• either free floating or attached to cells that
  they dont infect
• also occur if inoculated into lymphatics, can
  happen if replication occurs in the gut by the
  way of Peyers patches (GALT), no passage in
  blood stream, generates an immune response
• May come with spread of infected lymphatic cells
• HIV in lymphocytes
• other viruses as well
• Nervous system provides a route of spread for
  neurotropic viruses HSV and rabies,
• PNS into CNS
• HSV happens only rarely in humans, usually when
  decrease in the immune system

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Multiplication of Virus

• Symptoms are often defined by viral replication
  in target organs
• specific interaction between viral and cellular
  proteins viral proteins recognize specific
  features of favored cell types
• help to define tropism tissue virus likes
• host factors such as speed of immune response and
  inflammation also influences disease symptoms

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Tropism

• Requires distribution and occurrence of specific
  viral receptors
• Requires a specific spatial relationship
• virus and proteins on cell must come in close
  contact
• Poliovirus usually binds in intestinal mucosa and
  in lymphatic tissue but motor neurons have a
  related molecule and some strains can use this to
  get in and destroys the nerves causing paralysis
• Many examples of this phenomenon, some infections
  require co-receptor to help with infection or to
  spread
• Infection of the target tissue may not be
  associated with spread of a virus
• HIV may be spread without symptoms of the disease

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Later Stages Immunity

• Severity of disease is function of
• virus genotype
• amount of virl inoculum delivered to host
• hosts general immune competence
• Same virus can cause mild disease in one and
  severe disease in others
• Immune response is based on viral antigens
• effector T cells will kill cells expressing
  foreign Ag on their surface, also can help B
  cells make Ab, takes 7-10 days to mount this
  response generate long lived memory cells
  protect from subsequent infection
• Non-specific immune response
• INF, inflammation, macrophage destruction of
  infected cells, increase body temperature
  suboptimal for viral replication

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Later Stages Spread to New Hosts

• Symptoms of infection may lead to spread
• chicken pox can spread by rupture of vesicle and
  aerosol of the virus from the fluid
• hosts with lethargy caused by viral infection
  will lead to more mosquito bites and then they
  can pass on the virus

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Later Stages Fate of Host

• Host recovers or dies
• Most acute infections may clear
• May establish a latent infection in the host
• viral genome is present but not infectious virus
• Low level persistence
• Production of a syndrome not related to
  infection, usually much later
• Etiologies ultimate causative factors some
  diseases may be result of viruses