Promise for the new way to fight HIV

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Virus - Veni, Vidi, Vici ?
Izabela Tworowska, PhD Department of Biochemistry
and Cell Biology izabela7_at_rice.edu
Part II
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• Human Viruses
• Influenza
• Chickenpox
• Smallpox
• Polio
• Herpes
• Hepatitis C
• gt 80 chronic infection of the liver (
  fibrosis and cancer)
• Kills 500,000 people / yr
• Human Immunodeficiency Virus (AIDS)
• Enter through nose, mouth, breaks in
  the skin, body fluids, etc.
• Kills 3 million people / yr
• In 1999, 42 million people died
• http//www.economist.com/science

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Isolated in 1983 by R. Gallo (USA) and L.
Montagnier (France). Retroviruses with RNA
genome. The HIVs enzyme called reverse
transcriptase, produces DNA from RNA. (most
cells carry out the opposite process,
transcribing the genetic material of DNA into
RNA) Genetic information of HIV become
integrated permanently into the genome
(chromosomes) of a host cell.
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HIV infection

• binding to the CD4 receptor of HIV on the host
  cell (helper T lymphocytes)
• RNA, is released and undergoes reverse
  transcription into DNA,
• DNA enters the host cell nucleus and it can be
  integrated into the genetic material of the cell.
• transcription of viral DNA into messenger RNA
  (mRNA),
• mRNA is translated into viral proteins.
• the viral RNA and viral proteins assemble at the
  cell membrane into a new virus.
• the virus buds forth from the cell and is
  released to infect another cell.

primary hosts for HIV virus -
the white blood cells called helper T lymphocytes
MEDICAL PROBLEM The replication process of HIV
is associated with a very high mutation rate
(errors) . The evolution of HIV is a million
times more rapid than the evolution of humans.
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Anti-HIV
click to play a movie
2. Reverse transcriptase inhibitors
3. Protease inhibitors
1. Entry/fusion inhibitors
a) nucleoside/nucleotide analogs
AZT was one of the first nucleoside analogs
shown to have potent anti-HIV activity in-vitro
Thymidine
AZT
b) non-nucleoside analogs (heterocyclic
compounds)
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ENZYME (A3G)
(white blood cell)
Introduce changes to the HIV genetic code every
time the virus copies itself. The enzyme
corrupts the HIV genetic code
HIV
HIV


genetic code
STOP replication
destroy A3G
protein
Viral Infectivity Factor

Promise for the new way to fight HIV
DRUG
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Enemy are around us !

• 1918 - more than 20 million people died from a
  strain of the virus called Spanish flu
• USA- 25 to 50 million people contract influenza
  each year.
• Virion particles are spherical (80 - 120
  nanometers in diameter) and enveloped.
• Genome - single-stranded RNA (A and B
  forms only influenza C has 7 RNA segments).

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• Three distinct types of influenza virus- A, B,
  and C.
• Influenza A virus - affect a variety of
  animal species, causes epidemics
• Influenza B virus - only found in humans,
  responsible for many
• localized
  outbreaks.
• Influenza C virus is generally
  nonsymptomatic.

• Mutations in the protein (antigenic) structure of
  the influenza virus different influenza
  subtypes and strains forms. This is a gradual
  process known as antigenic drift. The body's
  immune system, cannot recognize the new influenza
  strain .
• The medical consequence
• The new influenza vaccines produced each
  year.
• Influenza strains can infect birds, pigs, and
  humans. The human strains
• and bird strains, may infect pigs,
  resulting in a unique virus.
• We cannot prepare vaccines in advance.
• The other antiviral medication amantadine
• (first used in the treatment the
  Parkinsons disease appears to prevent
• the influenza A virus from penetrating
  and entering healthy cells. )
• 
  

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• SARS
• (severe acute respiratory syndrome)
• Origin China, exported as far as Canada
• 774 people died , infected 8000
  (Nov 2002-May 003)
• Source Coronovirus,
• NEW RECOMBINANAT VIRUS
• Genome-DNA , combination of
  mammalian and avian viruses

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New Fashion Statement ?
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Bird Flu Virus

• Origin Asia (Thailand, Vietnam, Indonesia)
  2004
• Source the avian influenza virus H5N1 (the
  formal name)
• causes a severe respiratory
  infection,
• and potentially lethal
  encephalitis
• Report WHO in Thailand and Vietnam
• since 2004 , 92 people infected, 53 people died
• transmitted from poultry, then person-to-person
• Jan-March 2004 - 120 million poultry killed
• Danger the bird flu virus can mutate,
• constant genetic changes in
  the avian flu virus
• have made them difficult to
  control
• Indonesia- virus was found in
  pigs
• high genetic similarities
  between humans
• and pigs new virus strain can
  be created

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VIRUS IN STEALTH
to fight against cancer-lymphoma, and ovarian
cancer In 2004, 28000 Americans died of lymphoma
cancer. Traditional therapy chemoteraphy and
radiation The new approach redirect the virus
to attack diseased, rather than healthy
cells. Problems -this method works only
once -unintended creation of a super virus
capable of causing a new human disease.
Journal of
Virology, 2005, 08
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Vaccination

• Vaccination against many viruses still not
  possible
• Conventional vaccines consists of
• infectious (live)
• or non-infectious
  (killed) virus particle
• Vaccine SHOULD
• cause less severe disease than
  virus during natural infection
  stimulate the immune system (long-lasting
  immunity)
• be generally stable

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Virus strain virulent
avirulent
disease-causing virus
attenuated virus, causing mild symptoms
"Live virus " vaccine contains a "living" virus
that is able to give and produce immunity,
usually without causing illness or mild symptoms
Attenuation- the process of producing a virus
strain which causes a reduced amount of disease

• "Killed virus " vaccine
• 1. should cause no disease at all
• 2. contaminating viruses killed during the
  preparation process
• 3. disadvantages killed virus does not multiply
  
• higher immunizing dose
  hypersensitivity reactions
• increase the cost the therapy

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Poliomyelitis, or Polio 1. throat and intestinal
tract infections2. cold-like symptoms, pain and
stiffness in the neck, back, legs and in the
worst cases, paralysis or death 3. There are two
types of polio vaccine a)
Inactivated polio vaccine (killed virus,
IPV), given as a shot (the
polio virus used in this vaccine is killed)
b) live oral polio vaccine, (live
virus, attenuated, OPV) Currently in the
U.S. used only IPV, in parts of the world where
polio still exists people get vaccinated with OPV
(better at keeping the disease from spreading to
other people). However, in rare cases (about 1 in
2.4 million), OPV actually causes polio.
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IPV (dead polio virus) the virus is grown on
the cell culture and then killed with
formaldehyde or other chemicals harmful to the
virus the chemicals are removed before the dead
virus is added to the vaccine) OPV (live
polio virus, weakened, so does cause
disease)the virus is also grown in a lab on
monkey kidney cell cultureweakened using
chemicals, freezing and dilution before being
given to people as a vaccine.
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Some human and veterinary virus vaccines
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EXAM !
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