Interfering with Virus Replication

VIRAL INTERFERENCE

  1. SATELLITE AND HELPER VIRUSES

    1. Sets of such viruses to be discussed
      1. T2 + T4
      2. TNV + TNSV (to be covered under plant viruses)
      3. AV + AAV (ASV)
      4. SV40 + AV
      5. RSV + RAV + RIF (to be covered under oncoviruses)
      6. A contrived system: Lambda + Lambda-DNA

  2. INTERFERON

    1. Discovery by Jean Lindenmann et al
    2. Induction
    3. Structure (20 kdal protein)
    4. Mechanism of action
      1. Induction
      2. Transmembrane effects
      3. Induction of TIP-mRNA
      4. What TIP does
      5. Effect on RNA and DNA viruses
      6. Species specificity

  3. CHEMICAL INTERFERENCE

    1. Amantadine - an anti-adsorption agent for flu
    2. Designer drugs

SLIDES SHOWN

VIRAL INTERFERENCE OF SUPERINFECTION

Isabel Lester and Jean Lindenmann, M.D.
University of Massachusetts Medical Center
Boston, Massachusetts

Topics to be addressed:

  1. Why we rarely have two viral diseases simultaneously
  2. Why the immunocompromised generally die of bacterial and NOT of viral diseases.

Normally,

Historical note -
We observed that kids without antibodiesŠ

Of course -

Viruses consist of capsids and nucleocores.

The induction factor must be one of these:

  • Capsid
  • Nucleocore
  • Due to the infection itself

Other Interfering Substances

  • ssDNA (viral)
  • dsRNA (viral)
    (dsDNA interfers poorly)

BUT! A real genetic message is NOT importantŠ
...
Because artificial ssDNA's, ssRNA's, dsRNA's

ALSO WORK JUST AS WELL!

What is the biochemical nature
...of this thing we'll call "interferon"?

RNA, DNA, polysaccharide, lipid, protein, or something small like an endorphin?

INTERFERON is PROTEIN

And it's able to be electrophoresed.

Hmmm-, We obtained three bands that
...exhibited interferon activity.

Let's call them alpha, beta and gamma.

TYPES OF INTERFERON -

  • ALPHA: 15 different subtypes (isoelectric focusing); 143 aa; Chromosome 9; lymphocyte derived
  • BETA: 1 type; 145 aa; Chromosome 9; fibroblast derived
  • GAMMA: 1 type; 146 aa; Chromosome 12; lymphocyte derived

Maybe you're thinking we could use these to treat the common cold (reo- or rhinoviruses), or other common viral diseases (adenovirus-5) Š (nausea, fever)

How does INTERFERON interfere?

SUMMARY -

Our lines of defense against viral infection:

  1. No attachment sites on our cell surfaces (immediate)
  2. Restriction endonucleases (immediate)
  3. INTERFERON (3 hours to induce)
  4. Antibodies (initially 3+ days; thereafter 6 hours for the anamnestic response)

FUTURE APPLICATIONS

  • Treatment of cancers caused by viruses? (HIV)
  • Treatment of epidemics? (ebola, flu)

Brief History of Antibiotics -

  • Mercurials and Arsenicals
  • Sulfa Drugs
  • Penicillin
  • Streptomycin
  • AZT
  • Canavanine: an arginine analog
  • Amantadine