Summary of Virology Lectures 2018 #9: Reverse Transcription and Integration

Main Ideas and Concepts

• Reverse Transcription and Retroviruses

  The lecture focuses on Reverse Transcription, a process utilized by Retroviruses, which are viruses that contain reverse transcriptase in their reproductive cycle. Reverse transcriptase allows the conversion of viral RNA into DNA, contradicting the central dogma of molecular biology (DNA → RNA → Protein).

• Historical Discoveries

  The discovery of the first cancer viruses (e.g., Rous sarcoma virus) in the early 1900s led to the identification of tumor viruses with RNA genomes. Howard Temin and David Baltimore were pivotal in discovering reverse transcriptase, earning Nobel Prizes for their work.

• Mechanism of Reverse Transcription

  Reverse Transcription occurs in the cytoplasm, where viral RNA is converted into double-stranded DNA. The process involves a primer (usually tRNA) that initiates DNA synthesis, followed by template exchanges and degradation of the RNA by RNase H activity.

• Viral Genome Structure

  Retroviruses have a simple genome structure with genes organized into gag (structural proteins), pol (polymerase including reverse transcriptase), and env (envelope proteins). The integrated viral DNA (provirus) becomes a permanent part of the host cell's genome.

• Integration into Host DNA

  The enzyme integrase facilitates the integration of viral DNA into the host's chromosomal DNA, which is crucial for the viral lifecycle. This integration process results in the duplication of host DNA sequences at the integration site.

• Endogenous Retroviruses

  Endogenous Retroviruses are integrated viral sequences that can be passed down through generations. Human genomes contain about 8% endogenous retroviral DNA, remnants of ancient infections.

• Other Retro Elements

  The lecture discusses various mobile genetic elements in the human genome, including retrotransposons and LINEs (long interspersed nuclear elements), which can also move around the genome via Reverse Transcription.

• Comparison with Hepatitis B Virus

  Hepatitis B Virus, although a DNA virus, also utilizes Reverse Transcription in its lifecycle, with a unique mechanism that involves Reverse Transcription starting before the virus is released from the cell.

Methodology/Instructions

• Reverse Transcription Process
  1. Initiation: tRNA binds to the primer binding site (PBS) on the viral RNA.
  2. DNA Synthesis: Reverse transcriptase synthesizes a short DNA strand using the RNA template.
  3. Template Exchange: The enzyme switches to the 3' end of the RNA to continue DNA synthesis.
  4. RNA Degradation: RNase H activity degrades the RNA template.
  5. Second Strand Synthesis: A second strand of DNA is synthesized, leading to double-stranded DNA formation.
  6. Integration: The double-stranded DNA is integrated into the host's chromosomal DNA by integrase.

Speakers/Sources Featured

• The lecture appears to be conducted by an unnamed instructor, referencing historical figures such as Howard Temin and David Baltimore, as well as mentioning the Nobel Prize for their contributions to the understanding of reverse transcriptase and Retroviruses.

Notable Quotes

— 00:38 — « Sometimes I've believed as many as six impossible things before breakfast. »

— 04:50 — « The reverse transcriptase reverses the flow of genetic information. »

— 18:30 — « Life is an accident of reverse transcriptase and that generated what we now know as modern cellular life. »

— 61:27 — « If it weren't for retroviruses, we'd be laying eggs and they would be white. »

Category

Educational

Video