What is the difference between HSV-1 and HSV-2?

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What is the difference between HSV-1 and HSV-2?

• Both types infect the bodys mucosal surfaces,
  usually mouth or genitals, and then establish
  latency in the nervous system.
• For both types, at least two-thirds of the
  infected people have no symptoms, or symptoms too
  mild to notice.
• However, both types can recur and spread, even
  after a period in which there were no symptoms.

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The differences

• HSV-1 usually establishes latency in the
  trigeminal ganglion, a collection of nerve cells
  near the ear. Then it tends to recur on the
  lower lip or face.
• HSV-2 usually establishes latency in sacral
  ganglion at the base of the spine. From there,
  it recurs in the genital area.

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HSV-1

• However, one can have HSV-1 both genitally and
  orally.
• HSV-1 is usually mild, especially when it infects
  the lips, face, or genitals.
• However, HSV-1 can recur in the eye, causing
  ocular herpes, which can lead to blindness, and
  can even spread spontaneously to the brain,
  causing herpes encephalitis, which can lead to
  death.

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HSV-2

• 22 of adult Americans have HSV-2
• Like HSV-1, HSV-2 symptoms are usually mild, so
  mild, in fact, that two-thirds of infected people
  dont know they have it.
• HSV-2 rarely causes complications or spreads to
  other parts of the body.
• Oral HSV-2 infections are rare. But even when an
  infection does occur, recurrent oral outbreaks
  are uncommon.

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Transmission of HSV-2

• In the first year of HSV-2 infection, people shed
  the virus from the genital area about 6 to 10 of
  those days when they are asymptomatic. This
  decreases over time and can also be further
  lessened by the use of oral medication. Sex
  should be avoided in the presence of symptomatic
  lesions.
• Having a previous HSV-1 infection seems to
  provide some immunity to an HSV-2 infection.
  This is probably the reason that oral HSV-2
  infections are rare, given the studies which show
  that a significant proportion of the population
  practices oral sex.

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How severe an infection?

• HSV is a lifelong illness
• But HSV-2 usually produces only mild symptoms or
  signs or no symptoms at all. However, HSV-2 can
  cause recurrent painful genital sores in many
  adults, and HSV-2 infection can be severe in
  people with suppressed immune systems.
• Another factor is how long a person has had the
  infection. It seems to decrease in severity over
  time, for reasons which are unclear.

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Symptoms

• If signs and symptoms occur during the first
  episode, they can be quite pronounced. The first
  episode usually occurs within two weeks after the
  virus is transmitted, and the sores typically
  heal within two to four weeks.
• Other signs and symptoms during the primary
  episode may include a second crop of sores, or
  flu-like symptoms, including fever and swollen
  glands.

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Is there a cure?

• There is no treatment that can cure herpes, but
  antiviral medications can shorten and prevent
  outbreaks during the period of time the person
  takes the medication.

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Vaccines?

• NIH is now in the midst of Phase III clinical
  trial of an HSV-2 vaccine. This vaccine appears
  to be about 50 effective.
• If approved, it would be available in 2008.

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Antiviral Chemotherapy for HSV

• There are several prescription antiviral
  medications for controlling herpes outbreaks,
  include acyclovir (Zovirax), valacyclovir
  (Valtrex), famcyclovir (Famvir), and pencyclovir.
  
• Acyclovir was the original and prototypical
  member of this class
• Valacyclovir and famcyclovir are prodrugs of
  acyclovir and pencyclovir respectively, with
  improved oral bioavailability.

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Chemotherapy for HSV
Acyclovir (Zovirax)
Valacyclovir (Valtrex),
pencyclovir
Famcyclovir (Famvir),
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Mechanism of Action of Antivirals to treat HSV

• Both acyclovir and pencyclovir work by
  interfering with viral replication, effectively
  slowing the replication rate of the virus, and
  providing a greater opportunity for the immune
  response to intervene.
• All drugs in this class depend on the activity of
  the viral thymidine kinase to convert the drug to
  a monophosphate form and subsequently interfere
  with viral DNA replication.

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DNA Virus

• Recall that HSV is a DNA virus (influenza was an
  RNA virus)
• In general, more drugs are available to treat DNA
  viruses than for RNA viruses (excluding those
  used to treat HIV).
• Most of the drugs available for treatment of DNA
  viruses have been developed against
  herpesviruses.
• Diseases include cold sores, genital herpes,
  chickenpox, shingles, mononucleosis, etc.

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Acyclovir (ZOVIRAX)

• Discovered by random compound screening and
  introduced into the market in 1981.
• It was the first non-toxic herpes drug to be used
  systemically.
• It is used for the treatment of infections due to
  both HSV-1 and HSV-2.

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• Aciclovir interferes with DNA synthesis, but
  must first become activated.
• To become activated, Aciclovir must be
  phosphorylated (3x)
• However, Aciclovir itself is not a good
  substrate for mammalian kinases, thus it relies
  on the viral thymidine kinase to become
  phosphorylated the first time.
• This is good, since the drug cannot interfere
  with DNA synthesis in cells that are not infected
  with the virus, thus reducing the toxicity of the
  drug.
• The second and third phosphorylations, however,
  are performed by the cellular thymidylate kinase.

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• Aciclovir triphosphate is mistaken for
  deoxyguanosine triphosphate.
• However, since it lacks the 3-OH group, it
  cannot be linked to the adjacent residue in the
  usual fashion.

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