Know Your Enemy

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Know Your Enemy
MSV

• The maize streak virus (MSV) is an
  insect-transmitted virus that is endemic in
  sub-Saharan Africa.
• It is transmitted by an African leafhopper.
• It can in certain years devastate between 5 and
  100 of a farmer's maize crop.
• The development of resistant genetically modified
  maize varieties is currently under development in
  Africa.

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MSV

• Maize streak monogeminivirus .
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• Total genome size 2.69 kb.
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• Transmitted by a vector.
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Vector

• Vector is an organism that does not cause disease
  by itself, but which spreads the infection by
  conveying pathogens from one host to another.
• There are two types of vectors
• Mechanical vectors the virus does not multiply
  within mechanical vectors. Mechanical vectors
  only physically transport viruses from host to
  host.
• Biological vectors the viruses must multiply
  within a biological vector before the biological
  vector can transmit the viruses.

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Types of transmission

• There are four basic types of transmission
• Non-persistent Transmission
• These viruses are acquired from infected host
  plants through the probing behavior of the insect
  in very short periods of time. The insect then
  transmits the virus by probing on a healthy plant
  (5-30 seconds). Because the insect remains
  viruliferous (carrying or containing a virus )
  for only short periods of time, it must probe on
  infected plants to re-acquire the virus.
• Semi-persistent Transmission
• Viruses are acquired and transmitted by feeding
  rather than by probing. The longer the insect
  feeds, the greater the rate of transmission. The
  virus is retained for a few days and varies with
  the virus/vector combination. There is no latent
  period once the virus is acquired, it can be
  transmitted immediately.

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Types of transmission

• Circulative Non-propagative Transmission
• Viruses transmitted in this manner are also
  acquired and transmitted by the feeding rather
  than the probing behavior of the insect vector.
  There is an 8- to 12-hour latent period for the
  virus to get from the gut to the salivary glands,
  and longer feeding periods increase the chances
  of acquisition. Once the insect has acquired the
  virus, it can remain viruliferous for the
  remainder of its life. The insect is capable of
  transmitting the virus to numerous plants within
  its lifetime.
• Circulative Propagative Transmission
• These viruses are acquired and transmitted by
  feeding as well, but can also be acquired by
  transovarial transmission (passage from parent to
  progeny through the egg). These viruses replicate
  in both the plant and the insect and often have
  deleterious effects on both types of hosts.

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MSV - Transmitted by a vector

• Transmitted in a persistent manner.
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• Virus does not multiply in the vector.
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• Not transmitted congenitally to the progeny of
  the vector.
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MSV - Transmitted by a vector

• Not transmitted by mechanical inoculation.
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• Not transmitted by contact between plants.
• Not transmitted by seed not transmitted by
  pollen.
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Know Your Enemy
MSV

• In southern and central Africa, MSV is
  transmitted chiefly by Cicadulina mbila

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Latent Period
MSV

• MSV undergoes a latent period in the vector
  before transmission can occur.
• The length of this period is temperature
  dependent.
• At 30øC, the minimum latent period is 6 - 12
  hours, the medium period being 16 - 20 hours.
• At 16øC, the minimum latent period is 85 hours.
• The latent period represents the time required
  for the virus to pass from the insect's gut lumen
  to the salivary glands, where it becomes
  available for inoculation.

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Epidemiology
MSV

• Disease avoidance can be practiced by adjusting
  planting dates to avoid migrating leafhoppers
  landing on young plants.
• The vector can be controlled by applying systemic
  insecticides to the planting furrow during maize
  planting.

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MSV

• However, the development and use of
  streak-resistant cultivars is probably the most
  effective and economically viable means of
  preventing streak epidemics.
• Naturally occurring resistance to MSV has been
  found in maize on Reunion Island (where MSV has
  long been endemic). The resistance appeared to be
  simply inherited and was rapidly fixed in
  breeding, being easily transferred to other maize
  lines.

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MSV

• The incorporated resistance resulted in lowered
  disease incidence and reduced disease severity.
• More recently, it has been shown that resistance
  to MSV in maize is quantitatively inherited, with
  relatively small numbers of genes involved.
• Thus, it is envisaged that simple recurrent
  selection or modified back-cross breeding methods
  could be used to breed for MSV resistance in
  Africa.

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16
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17
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Patterns of infection
A delicate balance

• Natural infections can be rapid and self-limiting
  (acute infections) or
• Long-term (persistent infections)
• Variations and combinations of these two modes
  abound
• We can already provide detailed descriptions
• However, we are in the early days of
  understanding the molecular mechanisms required
  to initiate or maintain any specific one.

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Mechanisms of Survival of Viruses in Nature 

• Transmissibility related to virion release from
  the patient and quantity
• Seasonality affects the survival of viruses
• Community size determines if acute or
  persistence infections are perpetuated
• Effects of immunity types
• Antigenic drift, shift and reassortment 

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Mechanisms of Survival of Viruses in
Nature Persistent Infections

•  Herpesviridae,
• Adenoviridae,
• Papovaviridae,
• Hepadnaviridae,
• Arenaviridae, Togaviridae,
• Flaviviridae,
• Retroviridae.

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Mechanisms of Survival of Viruses in
Nature Persistent Infections

• Arenaviruses,
• Herpesviruses,
• Retroviruses
• and some Togaviruses

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Tropism

• viruses are not compatible with the biochemistry
  of all types of cells.
• The type of cell within a given individual host
  cell, which a virus can infect, is referred to as
  a virus' tropism.
• Tropism is a predilection of viruses to infect
  certain tissues and not others.
• An enterotropic virus replicates in the gut.
• A neurotropic virus replicates in the nerves.
• Some viruses are pantropic.
• HSV is often said to be neurotropic but in fact
  it is pantropic.
• Different species of viruses tend to vary both in
  their specific tropisms as well as in the breadth
  of their tropisms (i.e., they differ both in what
  cells they can infect and in how many different
  kinds of cells they can infect).

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Tropism

• an inability of the virus to successfully adsorb
  and/or enter cells because of an incompatibility
  between virus capsid proteins (or virus envelope
  proteins ) and the host receptor molecule
• an incompatibility between the biochemistry of
  the virus and the biochemistry of the host.
• some viruses infect one or only a few species
  while others (such as the rabies virus or
  poxviruses) are capable of infecting a broad
  range of species.
• Change in tropism can occur through virus
  mutation.

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Tropism
Example distemper on the Serengeti "Between
1993 and 1994, a CDV epidemic swept through
villages to the west of the Serengeti, killing
thousands of domestic dogs. Monoclonal antibody
tests show similarities between this strain and
the one that infected the lions. The researchers
propose that the virus then entered the park,
perhaps via jackals and spotted hyenas, which
frequently scavenge near humans. Because CDV is
shed in mucus, these animals, in turn, probably
infected lions at kill sites, where there is
often a lot of biting and snarling between
species. . . at least 1000 of the park's 3000
lions are thought to have died of the disease."
Other variants of CDV-like viruses have also been
identified which infect dolphins, horses, and
seals. (p. 596, Morell, 1996)
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Evasion of immune defense
Many viruses have evolved active mechanisms for
bypassing or disarming host defenses. For
example,
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Apoptosis (programmed cell death)
Many viruses have evolved active mechanisms for
bypassing or disarming host defenses. For
example,
Apoptosis is a process of deliberate suicide by
a cell in a multicellular organism. It is one of
the main types of programmed cell death , and
involves a series of biochemical events that lead
to the death of the cell. The apoptotic process
is needed to dispose of cell corpses and
fragments, for proper development and the
destruction of cells that represent a threat to
the integrity of the organism
some viruses express proteins that block the
apoptotic process that should activated in
virus-infected cells.
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Antigenic variation
Many viruses have evolved active mechanisms for
bypassing or disarming host defenses. For
example,

• Antigenic drift is the appearance of virus with a
  slightly altered surface protein (antigen)
  structure
• Antigenic shift is a major change in the surface
  protein. This process occurs when viruses with
  segmented genomes exchange genomes after
  coinfection.

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Influenza virus provides the classic paradigm of
antigenic drift and shift. Antigenic shift, not
drift, was the driving force for the five
pandemics of human influenza during the XIX-XX
centuries
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General patterns of infection
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• Acute ????? ????? ??? 7-10 ????
• Persistent ???????? ?????? ?????? (?? ??!) ???
  ????? ?????
• Latent
• Slow

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General patterns of infection

• The time when symptoms appear is indicated by the
  red shaded area, and the period in which
  infectious virus is released is indicated by the
  bracket.

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Acute infection

• An acute infection is an infection that develops
  rapidly and only lasts a short time, rapid
  production of virus followed by rapid resolution
  (SARS, influenza virus and rhinovirus).

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Acute infections present common public health
problems

• The nature of an acute infection presents
  difficult problems for physicians,
  epidemiologists, and others.
• The main problem is that by the time people feel
  ill most acute infections are essentially
  complete and the virus has spread to the next
  host.

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Multiple Acute infections in a Single Host

• Model of varicell-zoster virus infection and
  spread.

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Pathogenic Effects of an Acute Infection

• Many symptoms of an a.i. are actually due to a
  host immune response.
• Nevertheless, an acute viral infection can cause
  considerable damage because infected cells are
  killed either by infection or by the immune
  system.
• If a sufficient number of cells are infected,
  severe problems may result.

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Persistent Infections

• Infectious virus may be produced continuously or
  intermittently for months or years.
• virus is not cleared but remains in specific
  cells of infected individuals.
• Persistent infections may involve stages of both
  silent and productive infection without rapidly
  killing or even producing excessive damage of the
  host cells.
• Reactivation of a latent infection may be
  triggered by various stimuli, including changes
  in cell physiology, superinfection by another
  virus, and physical stress or trauma.

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Persistent Infections

• No measures to eradicate persistent viruses have
  been developed. Vaccination and antiviral drugs
  can reduce the frequency of clinical recurrence
  and symptoms, yet the virus continues to remain
  associated with the host.
• Distinctions have been made between p.i. (chronic
  infections) and latent/slow infections.
• Many viruses can establish a persistent
  infection.

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Persistent Infections
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Direct Infection of the Immune System Itself
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An Example of a Virus that Causes Persistent
Infections

• Measles Virus provides a provocative example of
  the delicate balance.
• Many important questions remain unanswered about
  how this human pathogen switches from an acute to
  a persistent infection.
• It does so despite an active immune response.

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Measles
Measles is one of the most contagious human
viruses, with about 40 million infections
occurring worldwide each year, resulting in 1 to
2 million deaths.
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Latent Infections

• Latent infections can be characterized by four
  general properties
• The cell cycle is interrupted
• Immune detection of the harboring cell is reduced
  or eliminated
• Expression of productive cycle viral genes is
  absent or inefficient
• The viral genome persists intact

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Latent Infections

• The latent genome can be maintained
• As a nonreplicating chromosome in a nondividing
  neuron (HSV)
• As an autonomous self-replicating chromosome in a
  dividing cell (EBV)
• Integrated into a host chromosome
  (adeno-associated virus)

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Latent Infections

• A latent infection is inactive though continuing
  to infect, and which remains capable of producing
  symptoms.
• "A latent disease is characterized by periods of
  inactivity either before signs and symptoms
  appear or between attacks.
• Herpes viruses are examples of pathogens which
  readily enter a latent stage during which
  symptoms disappear, only to reappear at a later
  time upon the reactivation of the latent
  infection.

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Latent Infections

• If latency is to have any values as a survival
  strategy, the latent virus must have a mechanism
  for reactivation so that it can spread to other
  hosts.
• Reactivation usually follows trauma, stress, or
  other insults

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Life cycle of HSV-1(productive infection)

• Entry by fusion
• Immediate-early genes transcription
• Early genes transcription
• Late gene expression
• Budding from nucleus
• Exocytosis

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HSV primary infection
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HSV latent infection

• Initiation occurs as in steps 1-7 of the
  productive infection
• Occurs primarily in neurons of sensory and
  autonomic ganglia
• Transcription is severe restricted

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HSV produces latent infection

• Over 40 million people in USA harbor latent HSV
  in their peripheral nervous system
• These cells are excluded from some forms of
  immune surveillance. They neither replicate their
  DNA nor divide.
• Sensory neurons are highly connected through
  synapses.

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HSV produces latent infection

• Once infected with HSV, the host is infected for
  life - latency is absolute persistence.
• Some individuals with latent HSV experience
  reactivation every 2 to 3 weeks, while others
  have rare or no episodes of reactivation.
• Among the signaling mechanisms are sunburn,
  stress, nerve damage, steroids, heavy metals, and
  trauma

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Epstein Barr Virus

• The primary site of EBV infection is the
  oropharyngeal cavity.
• The virus probably replicates in differentiating
  epithelial cells.

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B Cell Latency

• EBV infects B-lymphocytes and can cause
  infectious mononucleosis. (???? ??????)
• The virus can execute several distinct programs
  of gene expression which can lead to either a
  lytic cycle or latent infection.
• The lytic cycle results in producing infectious
  virions. The latent cycle (lysogenic) does not
  result in production of virions.
• A very limited, distinct set of viral proteins
  are produced during latent cycle infection. Six
  viral genes, termed EBNA 1-6 are expressed during
  this stage.

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B Cell Latency

• They transform the B cell into an immortal,
  continuously dividing cell.
• A small number of these "EBV-transformed" B cells
  circulate in the blood of healthy carriers.
• Their numbers are kept in check by the host's
  immune response.

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B Cell Latency

• A remarkable feature of EBV persistence is the
  equilibrium established between active immune
  elimination of infected cells and viral
  persistence.
• The signals that reactivate latent EBV infection
  are not well understood

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Slow Infections

• Slow infections are ones in which the infectious
  agents gradually increase in number over a very
  long period of time during which no significant
  symptoms are seen.
• Examples include AIDS (caused by HIV-1 and HIV-2)
  and certain lentiviruses that cause tumors in
  animals.
• Although not viruses, prions also cause slow
  infections (a type of infectious agent composed
  only of protein). Prions cause diseases of a
  neural tissue, such as mad cow disease in cattle
  and Creutzfeldt-Jakob disease in humans. All
  prion diseases are untreatable and fatal.