Viruses

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Viruses

• Are they living or not?

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Brief History of virus discovery

• Are agents that cant be seen with an ordinary
  light microscope
• Are agents that pass through filters that can
  trap even the smallest bacteria
• The question that arose was are these agents
  toxins or poisons?
• The Latin word for poisons is viruses

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Basic Virology

• What is a virus?
• Is it living or nonliving?
• How are they different from other living
  organisms?
• Submicroscopic 18-350 nm in size (10-9 M)
• Can only be seen with an electron microscope
• Obligate intracellular parasites
• Viruses have no genes that encode the proteins
  that function as the metabolic machinery for
  energy generation
• Viruses have no genes that encode the proteins
  that function as the metabolic machinery for
  protein synthesis
• Viruses may or may not contain the genes that
  encode enzymes involved in nucleic acid synthesis

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Basic Virology

• Biochemically
• Have RNA or DNA, not both
• Have no small ions or polysaccharides (sugars)
• May (enveloped viruses) or may not (naked
  viruses) contain lipids

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Basic Virology
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Basic Virology

• Growth curves of bacteria and viruses are very
  different

Viral growth curve
Bacterial growth curve
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Differences in growth curves

• Virus particles are produced from the assembly of
  pre-formed components other organisms grow from
  an increase in the integrated sum of their
  components and reproduce by cell division.
• Viruses dont grow or undergo division

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Basic Virology

• What is the basic structure of a virus?
• Nucleic acid of RNA or DNA is the genetic
  information for the virus
• Single (SS) or double stranded (DS)
• Linear, circular, or nicked
• Unsegmented or segmented
• If SS RNA, may be of the plus () or the minus
  (-) sense
• RNA genomic RNA can serve as mRNA and be
  directly translated into protein
• - RNA genomic RNA cannot serve as mRNA and
  cannot be translated directly into protein

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Basic Virology
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Basic Virology

• Protein outer coat is called the capsid
• The capsid is composed of individual subunits
  called capsomers
• What is the function of the capsid?
• Protects the delicate inner nucleic acid from
  harsh environmental conditions
• May be involved in attachment to host cells
• There are two basic capsid structures
• Icosahedral
• Helical

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Basic Virology
Icosahedral Structure
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Basic Virology
Helical structure
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Basic Virology

• Viruses that contain only the viral nucleic acid
  and the capsid are called naked viruses
• Some viruses have an outer lipid layer called an
  envelope
• The envelope is derived from host cell membranes
• For viruses that use the plasma membrane as their
  envelope, the envelope is acquired as the virus
  exits the host cell via a process called budding
• Virally encoded proteins in the envelope play a
  major role in the viral life cycle.
• Proteins in the viral envelope are involved in
  attachment to host cells.
• Proteins in the viral envelope mediate fusion of
  the virus envelope with host cell membrane during
  the entry of the virus into the host cell.

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Basic Virology

• Diagram of an enveloped virus (HIV)

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Basic Virology - budding
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Basic Virology

• What is required for a virus to successfully
  infect and replicate in a host cell?
• In order for a virus to successfully infect a
  host cell, the cell must contain the receptor
  that the virus binds to in the process of
  initiating an infection.
• The part of the virus that binds to the receptor
  is called the ligand.
• The ligand is on the capsid of naked viruses and
  on the envelope of enveloped viruses.
• gp 120 (the ligand) on HIV binds to CD4
  (receptor) and CXCR4 (co-receptor) on T
  lymphocytes or CCR5 (co-receptor) on macrophages

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Basic Virology
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Basic Virology

• In order for a virus to successfully replicate in
  a host cell, the host cell must not only contain
  the receptor for the virus, it must also have the
  cellular machinery that the virus needs for
  replication.
• The host range of a virus is the spectrum of host
  cells that the virus can successfully infect and
  replicate in.
• If the virus successfully replicates in the host
  cell, the infection is productive and the host
  cell is said to be permissive for the virus.

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Basic Virology

• If the cell lacks something required for viral
  replication, the infection is abortive or
  non-productive and the host cell is considered to
  be non-permissive for the virus.
• What are the basic features of the viral life
  cycle?
• Attachment or adsorption ligand on virus binds
  to a receptor on a host cell
• Penetration virus gets inside the host cell
• Penetration of naked viruses usually involves
  either
• Receptor mediated endocytosis or
• Formation of a pore in the host cell plasma
  membrane through which the nucleic acid and
  possibly associated viral proteins enter the
  cytoplasm

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Basic Virology

• Penetration of enveloped viruses occurs through a
  fusion event between the viral envelope and a
  host cell membrane.
• Uncoating separation of capsid and nucleic acid
  in preparation of viral transcription and nucleic
  acid replication (attachment and penetration may
  occur simultaneously)

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Basic Virology

• Biosynthesis viral proteins are made and viral
  nucleic acid is replicated
• RNA viruses must bring in their own enzyme(s) for
  transcribing their mRNAs and replicating their
  genome. This is because neither prokaryotic
  cells nor eukaryotic cells contain enzymes that
  can use RNA as a template to make a complementary
  copy of RNA. Therefore, most RNA viruses
  replicate entirely within the cytoplasm.

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Basic Virology

• DNA containing viruses can either use the host
  enzymes to transcribe their mRNAs and replicate
  their genomes, or they may bring in their own
  enzymes for these processes
• Retroviruses are unique RNA viruses in that they
  bring in an enzyme called reverse transcriptase
  (RT). RT makes a double stranded DNA copy of the
  viral RNA genome. This DNA then moves to the
  nucleus where it is incorporated into the DNA of
  the host cell. It is only after this occurs that
  the viral genes are transcribed and translated
  into protein products.

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Basic Virology

• Assembly or maturation All of the viral
  components assemble into new viruses. This does
  not occur until a sufficient number of viral
  proteins are made and viral genomes are
  replicated
• Release newly made viruses exit the host by
  lysis or budding

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Basic Virology
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Basic Virology

• How are viruses classified?
• The most commonly used classification scheme is
  the Baltimore scheme. This scheme is based on the
  relationship between the viral genome and the
  mRNA used for translation during expression of
  the viral genome

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Baltimore Classification of Viruses
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Basic Virology

• Effects of the virus on the host cell even
  though you cant see the virus, you can see the
  effects that the virus has on the host cell
• Death of the cell often occurs on release of
  the virus
• Cytopathic effects are visible effects on the
  host cell caused by viral replication
• Cancer
• Requires that the virus integrates all or part of
  its genome into the host cell DNA

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Overview of viral infections

• Viral diseases of the skin
• Warts
• Caused by human papilloma virus (double stranded
  DNA)
• Spread by direct contact
• Treated with acids or cryotherapy
• Smallpox (variola)
• Caused by variola major (mortality gt20) and
  minor (mortality lt 1) (double stranded DNA)
• Transmitted by respiratory route
• Virus moves from respiratory tract to the
  bloodstream to the skin to cause a pustular rash
• Leaves disfiguring scars

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Smallpox lesions
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Overview of viral infections

• Other symptoms include fever, malaise, severe
  backache and abdominal pain
• Vaccination has successfully eradicated this
  disease
• Problem use in bioterrorism
• Chickenpox and shingles
• Caused by varicella-zoster (a herpes virus -
  double stranded DNA)
• Infection is through the respiratory route
• Incubation is 2 weeks, but the infected
  individual is contagious at this stage
• Virus localizes in the skin to cause a vesicular
  rash with vesicles that fill with pus, rupture,
  and form scabs
• After chickenpox the virus remains latent in
  nerve cells and can be reactivated later in life
  to cause shingles

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Overview of viral infections

• Shingles is characterized by severe pain due to
  inflammation of the nerve branches of the
  cutaneous sensory nerves around one side of the
  trunk.
• A vaccine to prevent chickenpox is now available

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Chicken pox and shingles
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Overview of viral infections

• Measles (rubeola)
• Caused by a paramyxovirus (single stranded
  sense RNA)
• Is highly contagious
• Spread by the respiratory route
• Incubation 10-12 days
• Symptoms are similar to the common cold plus a
  papular rash (small, raised spots)
• Koplik spots (red patches with central white
  specks) in the oral cavity are diagnostic

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Overview of viral infections

• Severe complications include encephalitis,
  pneumonia, ear infections, and even death
• May later cause subacute sclerosing
  panencephalitis with progressive nerve
  destruction and death
• A vaccine is available (part of the MMR
  Measles, Mumps, and Rubella)
• We should be able to eradicate this virus since
  man is the only known host

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Measles (rubeola)
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Overview of viral infections

• German measles (rubella)
• Caused by a togavirus (single stranded sense
  RNA)
• Transmitted via the respiratory route
• Symptoms include a slight fever and a rash of
  small red spots.
• Infection during the first trimester of pregnancy
  can lead to birth defects (deafness, eye
  cataracts, heart defects, mental retardation) or
  death of the fetus
• Vaccination via MMR

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German measles (rubella)
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Overview of viral infections

• Cold sores
• Caused by herpes simplex virus (HSV), type I
  (double stranded DNA)
• Characterized by lesions of the oral mucous
  membranes
• Following the initial infection, the virus may
  remain latent in the nerves
• Physical or emotional stress may cause a
  reactivation of the latent infection
• Viral diseases of the eye
• Corneal lesions caused by HSV, type I can lead to
  blindness or CNS invasion

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HSV I infections
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Overview of viral infections

• Viral diseases of the respiratory tract
• The common cold
• Caused mainly by rhinoviruses (single stranded
  sense RNA) and coronaviruses (single stranded
  sense RNA)
• gt200 different types of viruses can cause the
  common cold!
• Spread by respiratory secretions on the hands
• Symptoms include sneezing, nasal discharge, and
  congestion
• Influenza
• Caused by orthomyxoviruses (segmented, single
  stranded sense RNA viruses)

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Overview of viral infections

• Transmitted via respiratory secretions
• Symptoms include fever, chills, headache, and
  general muscle aches
• These organisms are continually changing their
  antigenic structure by shift and drift making it
  difficult to develop effective vaccines
• Shift occurs with genetic recombination or gene
  reassortment
• Drift occurs by mutations
• Viral diseases of the central nervous system
• Meningitis or encephalitis

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Overview of viral infections

• These are infections of the membranes that cover
  the brain and spinal cord or of the brain itself
• Many different viruses can cause meningitis and
  encephalitis
• Organisms that enter through the blood need to
  cross the blood-brain barrier to cause disease.
• Other organisms move along peripheral nerves to
  the CNS
• Viral meningitis is often called aseptic
  meningitis because no bacteria or fungi can be
  cultivated from the CSF

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Overview of viral infections

• Poliomyelitis (polio)
• Caused by a picornavirus (small single stranded
  sense RNA)
• There are three different serotypes of poliovirus
• Transmission occurs via the gastrointestinal
  tract after ingestion of fecal contaminated water
• Symptoms include fever, sore throat, and headache
• In 1-2 of the cases (mainly in adults) the virus
  penetrates the capillary walls and enters the CNS
  where it it multiplies in the motor nerve cells
  eventually killing them and causing paralysis
• Two vaccines have been used
• Salk virus inactivated by formalin

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Overview of viral infections

• Sabin live, attenuated virus ( recently
  reactivation problems have resulted in the
  discontinuation of the use of this vaccine)
• Rabies
• Caused by a bullet-shaped rhabdovirus (single
  stranded sense RNA)
• Transmission is via the saliva of a rabid (rabies
  infected) animal
• Virus travels along the peripheral nerves to the
  CNS where it causes encephalitis
• Symptoms include painful spasms of the muscles of
  the mouth and pharynx when swallowing liquids
  (hydrophobia)
• Treatment is with rabies immune globulin followed
  by active immunization

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Rabies
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Overview of viral infections

• Viral diseases of the cardiovascular system
• Myocarditis inflammation of the heart muscle
• Caused by many different organisms, but is
  commonly caused by Coxsackieviruses (single
  stranded sense RNA)
• Infection occurs via the respiratory route or via
  the gastrointestinal tract
• The organism gains access to the heart via the
  bloodstream or the lymphatics

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Overview of viral infections

• Infectious mononucleosis
• Caused by Epstein-Barr virus (a herpes virus
  double stranded DNA)
• Transmission is via saliva and hence the disease
  is often called the kissing disease
• Symptoms include fever, sore throat, swollen
  lymph nodes, and general weakness
• Like all herpes virus infections, after the
  primary infection the virus remains latent, this
  time in B lymphocytes

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Overview of viral infections

• The virus has been linked to three human cancers
• Hodgkins disease
• Burkits lymphoma
• Nasopharyngeal carcinoma

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Burkitts lymphoma
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Overview of viral infections

• Viral hemorrhagic fevers
• Caused by several different types of virus
• Ebola virus causes this type of disease
• Are transmitted from human to human
• Have a high mortality rate from hemorrhaging and
  shock

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Ebola hemorrhagic fever
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Overview of viral infections

• Viral disease of the digestive system
• Mumps
• Caused by a paramyxovirus (single stranded
  sense RNA)
• Transmission is via salivary secretions and
  portal of entry is the respiratory tract
• Incubation is 16-18 days during this time the
  virus moves from the respiratory tract to the
  bloodstream to the parotid (salivary) glands and
  testes in males
• Symptoms include swelling, fever, painful
  swallowing and occasionally sterility.
• Vaccination is via the MMR

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Mumps
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Overview of viral infections

• Hepatitis an inflammation of the liver
• Hepatitis A (single stranded sense RNA)
• Causes infectious hepatitis
• Is transmitted via the fecal-oral route
• Symptoms include anorexia, malaise, nausea,
  diarrhea, abdominal discomfort, fever and chills
  for 2-21 days
• 2/3 of infected individuals have jaundice which
  is indicative of liver damage

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Overview of viral infections

• Hepatitis B (double stranded DNA virus)
• Causes serum hepatitis
• Is transmitted through the blood
• Incubation is 4-26 weeks
• Symptoms range from subclinical to severe fever
  and headache with jaundice
• 90 recover completely and 10 become chronic
  carriers and have a high incidence of liver
  disease including hepatoma
• A vaccine is available
• Hepatitis C (double stranded DNA virus)
• Causes serum hepatitis
• Is transmitted through blood
• The disease is clinically similar to that of
  hepatitis B

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Overview of viral infections

• Viral gastroenteritis
• In children is most commonly caused by rotavirus
  (double stranded RNA) or adenoviruses (double
  stranded DNA)
• Symptoms include fever, diarrhea, and vomiting
• Viral diseases of the reproductive system
• Genital herpes

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Overview of viral infections

• Caused by herpes simplex virus (HSV), type II
  (double stranded DNA)
• Incubation is 1 week
• Symptoms include painful vesicular lesions
  containing infectious fluid.
• This virus also becomes latent in nerve cells and
  can be reactivated to cause the same type of
  lesions found in the primary infection
• This virus can cross the placenta to infect the
  fetus leading to mental retardation and defective
  sight and hearing
• The fetus can also be infected during the
  delivery, therefore all women positive for this
  virus routinely deliver their babies by a C-
  section

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HSV II infection
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Overview of viral infections

• Genital warts
• Caused by human papilloma viruses (double
  stranded DNA viruses)
• Some strains of these viruses can cause cervical
  cancer

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Genital warts
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Overview of viral infections

• Prions
• Cause diseases that were formerly called slow
  viral infections
• Prions are not viruses they have no nucleic acid
  associated with them
• Prions are infectious proteins
• They cause a misfolding of a normal cellular
  protein counterpart
• They cause neurological diseases characterized by
  a spongiform encephalopathy that results in
  eventual death
• Examples include

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Overview of viral infections

• Kuru
• Creutzfeldt-Jakob disease
• Mad cow disease

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Prion diseases