RNA and DNA Viruses

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RNA and DNA Viruses
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Viruses

• disease-causing agents that can multiply only in
  cells
• viruses are DNA or RNA enclosed by a protective
  coat that enables them to move from one cell to
  another.
• Viral-infected cells often break open (lyse) and
  allows viruses access to nearby cells.
• A protein shell (capsid) surrounds the nucleic
  acid of most viruses. In many viruses the protein
  capsid is further enclosed by a lipid bilayer
  membrane that contains proteins.

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Viral capsid
The capsids of some viruses, all shown at the
same scale. (A) Tomato bushy stunt virus (B)
poliovirus (C) simian virus 40 (SV40) (D)
satellite tobacco necrosis virus.
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Acquisition of a viral envelope
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The Coats of Viruses
Adenovirus, a DNA-containing virus that can
infect human cells. The protein capsid forms the
outer surface of this virus.
Bacteriophage T4, a large DNA-containing virus
that infects E. coli.
Influenza virus, a large RNA-containing animal
virus whose protein capsid is enclosed in a lipid
envelope with protruding spikes of viral
glycoprotein
Potato virus X, a filamentous plant virus that
contains an RNA genome.
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Several types of viral genomes
The smallest viruses contain only a few genes and
can have an RNA or a DNA genome the largest
viruses contain hundreds of genes and have a
double-stranded DNA genome.
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T4 bacteriophage chromosome
This schematic shows the positions of the more
than 30 genes involved in T4 DNA replication. The
genome of bacteriophage T4 consists of 169,000
nucleotide pairs and encodes about 300 different
proteins.
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The life cycle of the Semliki forest virus
The virus parasitizes the host cell for most of
its biosyntheses
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The life cycle of a retrovirus

• The retrovirus genome consists of an RNA molecule
  of about 8500 nucleotides two such molecules are
  packaged into each viral particle.
• The enzyme reverse transcriptase first makes a
  DNA copy of the viral RNA molecule and then a
  second DNA strand, generating a double-stranded
  DNA copy of the RNA genome.
• The integration of this DNA double helix into the
  host chromosome, catalyzed by the viral enzyme
  integrase, is required for the synthesis of new
  viral RNA molecules by the host-cell RNA
  polymerase.

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reversetranscription
messenger RNA (mRNA)
transfer RNA (tRNA)
ribosomal RNA (rRNA)
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The life cycle of a retrovirus
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The AIDS Virus Is a Retrovirus

• In 1982 physicians first became aware of a new
  sexually transmitted disease that was associated
  with an unusual form of cancer (Kaposi's sarcoma)
  and a variety of unusual infections. Because both
  of these problems reflect a severe deficiency in
  the immune system - specifically in helper T
  lymphocytes - the disease was named acquired
  immune deficiency syndrome (AIDS). By culturing
  lymphocytes from patients with an early stage of
  the disease, a retrovirus was isolated that is
  now known to be the causative agent of AIDS.
• The retrovirus, called human immunodeficiency
  virus (HIV), enters helper T lymphocytes by first
  binding to a functionally important plasma
  membrane protein called CD4. There are two
  features of HIV that make it especially deadly.
  First, it eventually kills the helper T cells
  that it infects rather than living in symbiosis
  with them, as do most other retroviruses, and
  helper T cells are vitally important in defending
  us against infection. Second, the provirus tends
  to persist in a latent state in the chromosomes
  of an infected cell without producing virus until
  it is activated by an unknown rare event this
  ability to hide greatly complicates any attempt
  to treat the infection with antiviral drugs.
• Much current research on AIDS is aimed at
  understanding the life cycle of HIV. The complete
  nucleotide sequence of the viral RNA, which
  encodes nine genes, has been determined. This has
  made it possible to identify and study each of
  the proteins that it encodes. The
  three-dimensional structure of its reverse
  transcriptase is being used to help design new
  drugs that inhibit the enzyme.

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A map of the HIV genome
The HIV genome is about 9000 nucleotides and
contains nine genes. Three of the genes (green)
are common to all retroviruses gag encodes
capsid proteins, env encodes envelope proteins,
and pol encodes both the reverse transcriptase
and the integrase proteins. The HIV genome
contains six small genes (in red) plus the three
(in green) that are normally required for the
retrovirus life cycle.
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1. Attachment CD4-gp120 Interaction
Gp120-Chemokine Receptor Interaction 2. Viral
Fusion/Uncoating 3. Reverse Transcription
4. RNaseH Degradation 5. Second Strand
Synthesis 6. Migration to Nucleus
7. Integration 8. Latency 9. Early
Transcription 10. Late Transcription 11. RNA
Processing 12. Protein Synthesis 13. Protein
Glycosylation 14. Assembly of Virion 15. Viral
Budding 16. Virion Maturation
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Web links for HIV life cycle http//www.hopkins-a
ids.edu/hiv_lifecycle/hivcycle_txt.html
http//www.sumanasinc.com/webcontent/anisamples/
microbiology/hiv.html
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HIV binds to the CD4 receptor on the host cell.
CD4 is present on the surface of many
lymphocytes, which are a critical part of the
body's immune system. A coreceptor, CXCR4 and/or
CCR5, is needed for HIV to enter the cell.
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The HIV envelope fuses with the host cell
membrane.
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The viral capsid and its contents enter the host
cell
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The RNA HIV genome and the enzyme reverse
transcriptase are released in to the host cell
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Reverse transcriptase makes a DNA copy of the RNA
HIV genome. First, a single-stranded DNA is made
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Reverse transcriptase then makes a
double-stranded DNA copy of the HIV genome
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The enzyme integrase fuses the double-stranded
copy of the DNA genome with the host cell genome
in the nucleus
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mRNA is produced encoding HIV proteins
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mRNA is translated to produce HIV-encoded
polypeptides, including HIV protease
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HIV protease cleaves polypeptides and makes
functional HIV proteins
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A new HIV particle is assembled at the cell
surface and buds off
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The HIV virus particle leaves to infect other
cells
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Human immunodeficiency virus (HIV) leaving an
infected T lymphocyte
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Preventing and treating AIDS
Vaccines?
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Preventing and treating AIDS
Vaccines?
Modern vaccines for viral infections often
consist of one or more coat proteins of the
virus that are not themselves infectious, but
elicit an immune response from the person
receiving the vaccine.
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Preventing and treating AIDS
Vaccines?
Modern vaccines for viral infections often
consist of one or more coat proteins of the
virus that are not themselves infectious, but
elicit an immune response from the person
receiving the vaccine. HIV reverse transcriptase
has an error rate of one nucleotide per 2000.
This means that the amino acid sequence of the
HIV coat proteins is constantly changing.
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Preventing and treating AIDS
Drugs? What should we target?
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Anti-HIV chemotherapy

• Antiretroviral Agents Currently Available
  (generic name/Trade name)
• zidovudine/Retrovir (AZT, ZDV)
• didanosine/Videx, Videx EC (ddI)
• zalcitabine/HIVID (ddC)
• stavudine/Zerit (d4T)
• lamivudine/Epivir (3TC)
• abacavir/Ziagen (ABC)
• nevirapine/Viramune (NVP)
• delavirdine/Rescriptor (DLV)
• efavirenz/Sustiva (EFV)
• tenofovir DF/Viread (TDF)
• indinavir/Crixivan
• ritonavir/Norvir
• saquinavir/Invirase, Fortovase
• nelfinavir/Viracept
• amprenavir/Agenerase
• lopinavir/ritonavir, Kaletra
• FUZEON (enfuvirtide, ENF or T-20)
• Anti-PDI antibodies