Family Picornaviridae

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• Family Picornaviridae
• 1.Genus Enterovirus
• Type Species poliovirus 1
• 2.Genus Rhinovirus
• Type Species human rhinovirus 1A
• 3.Genus Hepatovirus
• Type Species hepatitis A virus 1
• 4.Genus Cardiovirus
• Type Species encephalomyocarditis
  viris
• 5.Genus Aphthovirus
• Type Species foot-and-mouth disease
  virus

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Picornaviruses

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  ????? ????? ??"? ????? ???.
• non-enveloped
• positive single-stranded RNA
• an icosahedral capsid
• around 28 nm in diameter
• The diseases they cause are varied acute
  "common-cold (rhinovirus A), hepatitis A, polio
  virus and many more.
• Two main categories are enteroviruses and
  rhinoviruses.

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Note the icosahedral symmetry which is clearly
visible in this image.
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Picornaviruses
Introduction

• Picornaviruses are among the most diverse (more
  than 200 serotypes) and 'oldest' known viruses
  (temple record from Egypt ca. 1400 b.C.).
• Poliomyelitis as a viral disease was first
  recognized by Landsteiner and Popper, 1909
  (though the virus was not isolated until the
  1930's).

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Picornaviruses
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• Genomic RNA is infectious - CHARACTERISTIC OF
  ()SENSE RNA VIRUSES !!!
• There is a long (600-1200 base) untranslated
  region at the 5' end and a shorter 3'
  untranslated region (50-100 bases) - important in
  (-)strand synthesis.
• The rest of the genome encodes a single
  'polyprotein' of between 2100-2400 aa's.

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Picornaviruses
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Picornaviruses
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• The capsid is an arrangement of 60 protomers in a
  tightly packed Icosahedral structure. Each
  protomer consists of 4 polypeptides known as VP
  (viral protein) 1, 2, 3 and 4. All of these VP
  polypeptides originate from one protomer known as
  VP0 (VP0 is cleaved to give the different capsid
  components).

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At the 5 end or their genome, picornaviruses
have a virally encoded protein known as VPg. This
protein is used as a primer for transcription by
RNA polymerase. This protein also tags the
virus's RNA, so that it can be differentiated
from host RNA.
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Polioviruses
Life cycle

• 0. The viral particle binds to cell surface
  receptors.
• Uncoating
• VPg protein removed
• Translation in the cytoplasm
• ----
• Cleavage of viral proteins
• Transport to the nucleus
• RNA synthesis
• Plus to minus
• Minus to plus
• Some strands translated
• Cleavage
• Virion assembly
• Release

Replication
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Life cycle

• http//americanhistory.si.edu/polio/virusvaccine/l
  ivingchem.htm

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Picornaviruses
Replication

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Picornaviruses
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• Notice, that the viral genome is translated by
  host cell machinery in the cytoplasm. This is
  very rapid with the whole process of replication
  being completed on average within 8 hours.

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Picornaviruses
Classification

• Aphthovirus 7 serotypes
• Cardiovirus 2 serotypes
• Enterovirus 111 serotypes
• Hepatovirus 2 serotypes
• Rhinovirus 105 serotypes
• Total 230 viruses

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Picornaviruses Enteroviruses

• Enteroviruses

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Rhinoviruses

• Cause of 'the common cold' (but not the only
  one!). 105 serotypes and new strains appear
  continually (hence repeated infections).
• Little consequence in itself, but predisposes to
  secondary bacterial infections - a major problem
  in infants and elderly.
• many people would say that the lack of a cure for
  the common cold is one of the great failings.
• The difficulty of creating a vaccine for the
  common cold lies in the diversity of rhinovirus.
• Antiviral drugs, however, are a possible
  solution.

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Polioviruses

• They cause poliomyelitis (flaccid muscular
  paralysis).
• As with all the Enteroviruses, they are
  transmitted by the faecal-oral route.
• These are the prototypic Picornaviruses there
  are 3 distinct serotypes.

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• Antibodies bind to the surface of rhinovirus and
  poliovirus in this same position and block their
  attachment to the surfaces of cells.

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rhinovirus is bound to a receptor protein on the
cell surface, shown in blue.
fragments of antibodies (in light blue) bound to
rhinovirus.
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• The intact antibodies are much larger than the
  small fragments seen here, so seven to ten
  antibodies are enough to form a bulky barrier on
  each virus to block attachment and infection.

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• Poliomyelitis

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  Popper , 1909, ??? ????? ???? ?? ????? ???????.
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  ?-40 ?????? ?-50 ????? ??????? ?? ?????. ????? ?-
  40 ????? ?????? ?? ?? ???"?, ?????? ????? ??????.

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Poliovirus

• Poliovirus is spreads easily via human-to-human
  contact, but cannot naturally infect other
  species.
• The infection is passed on to others via the
  fecal-oral route.
• Two basic patterns of polio infection are
  described a minor illness which does not involve
  the central nervous system, and a major illness,
  which may be paralytic or non-paralytic.
• In about 3 of poliovirus infections, the virus
  enters the central nervous system. In 12 of
  infections patients develop symptoms of headache,
  neck, back, abdominal and extremity pain, fever,
  vomiting, lethargy and irritability.
• In approximately 1 in 200 to 1 in 1000 cases
  poliovirus infection leads to the development of
  paralytic disease, in which the muscles become
  weak and poorly controlled, and finally
  completely paralyzed.

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• passive immunization- In 1950 William Hammon
  isolated serum, containing antibodies to
  poliovirus, from the blood of polio survivors.
• the serum was shown to be about 80 effective in
  preventing the development of paralytic
  poliomyelitis.
• The passive immunization approach was later
  deemed impractical for widespread use, due to the
  limited supply of blood plasma.

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Weller, Enders Robbins

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Weller, Enders Robbins

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  ?????? ??????? ???? ??? ???, ?????? ???? 1949,
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  ?????.

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The Nobel Prize in Physiology or Medicine 1954
"for their discovery of the ability of
poliomyelitis viruses to grow in cultures of
various types of tissue"
John Franklin Thomas Huckle Frederick
Chapman Enders Weller
Robbins
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Jonas SalkThe Salk vaccine

• inactivated poliovirus vaccine - is based on
  poliovirus grown in a type of monkey kidney
  tissue culture, which are then inactivated with
  formalin.
• Salk observed that it is possible to acquire
  immunity through contact with inactivated
  (killed) virus. Using formaldehyde, Salk killed
  the poliovirus, but kept it intact enough to
  trigger the necessary immune response.
• After successful tests, in 1952, Salk tested his
  vaccine on volunteering parties, including
  himself, the laboratory staff, his wife, and his
  children.
• After the vaccine became available, polio cases
  in the U.S. dropped by 85-90 percent in only two
  years.

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Dr. Jonas Salk

• Salk Jonas Edward, born on October 28, 1914, to
  Russian-Jewish immigrant parents, who were
  neither formally educated nor rich enough to
  educate their children, Salk was the eldest
  amongst his siblings and had a keen desire to
  learn. As a child, Salk was not actually
  interested in science.
• He was interested in humans and this motivated
  and intrigued him the most.

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Dr. Jonas Salk

• In 1947, Salk accepted an appointment to the
  University of Pittsburgh Medical School.
• While working there, with the National Foundation
  for Infantile Paralysis, Salk got an opportunity
  to develop a vaccine for one of the most dreaded
  diseases polio.

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Jonas Salk

• After the development of the polio vaccine, he
  founded an institute for medical studies where he
  continued working towards the cause and
  prevention of other deadly diseases like cancer
  and AIDS. He also wrote several books, that dealt
  with peace and mankind in general.
• He died at the age of 80, before he could make
  his second research see the light of the day.

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Jonas Salk

• Salk did not seek wealth or fame through his
  innovations, famously stating, "Who owns my polio
  vaccine? The people! Could you patent the sun?"

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Albert Sabin

• Albert Sabin developed an oral polio vaccine
  (OPV) using live but weakened virus, produced by
  the repeated passage of the virus through
  non-human cells at a sub-physiological
  temperature.
• The live-virus oral vaccine developed by Albert
  Sabin became the preferred alternative. The Salk
  vaccine needs to be injected. But the Sabin
  vaccine can be taken orally - the advantage of
  easier delivery. There were pros and cons to
  each, but the oral vaccination won out.
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Advantages of Sabin's Vaccine

• oral vaccine - the advantage of easier delivery,
  especially in less developed countries.
• the live vaccine gives both intestinal and bodily
  immunity the killed vaccine of Salk gives only
  bodily immunity and allows the immune person to
  still serve as a carrier or transmitter.
• the Sabin vaccine produces lifelong immunity
  without the need for a booster shot or
  vaccination.

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Child receiving polio vaccine
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Sabin, Albert Bruce 1906-1993
American physician and microbiologist, b.
Bialystock, Russia, grad. New York Univ. (B.S.,
1928 M.D., 1931). He emigrated to the United
States in 1921 and was naturalized in 1930. He
conducted research on viral and other infectious
diseases and developed (c.1959) a live-virus
vaccine for immunization against poliomyelitis.
The Sabin vaccine may be taken orally and
provides longer immunity than the killed-virus
vaccine. Also, the killed-virus vaccine protects
only against paralysis, whereas the live vaccine
guards against both paralysis and infection.
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Dr. Sabin's Vaccine

• In 1957 the World Health Organization (WHO)
  decided Dr. Sabin's vaccine deserved world-wide
  testing.
• He was invited to administer the vaccine to large
  groups of children in parts of Russia, Holland,
  Mexico, Chile, Sweden, and Japan.

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Dr. Sabin's Vaccine

• But at home in the United States, he had a hard
  time convincing the Poliomyelitis Foundation and
  the U.S. Public Health Service his method was any
  better than Jonas Salk's "killed" vaccine method.

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• There are three different serotypes of
  poliovirus, poliovirus type 1 (PV1), type 2
  (PV2), and type 3 (PV3), each with a slightly
  different capsid protein, but which produce the
  same disease symptoms.
• After two doses of inactivated polio vaccine
  (IPV), ninety percent or more of individuals
  develop protective antibody to all three
  serotypes of poliovirus, and at least 99 are
  immune to poliovirus following three doses.