Viral Replicative Cycles Flashcards

Viral Replicative Cycles

Introduction

  • Once viral nucleic acid is released into a host cell, the subsequent steps in the replicative cycle depend on the nature of the genetic material (DNA or RNA).

DNA Viruses

  • Most common DNA viruses are double-stranded DNA (ds-DNA) viruses.
  • Best-studied examples:
    • Phage T4 (virulent).
    • Lambda (λ) phage (temperate).
    • Virulent phages follow a lytic pathway, leading to the production of new viral particles and their release from the host cell.
    • Temperate phages can follow either a lytic or a lysogenic pathway. The lysogenic pathway involves a period of dormancy, from which the phage can exit at a later time.

Replicative Cycle of Virulent Phage T4

  1. Replication of viral DNA
  2. "Early" viral mRNA Transcription by host RNA polymerase
  3. Translation: Synthesis of "early" viral proteins
  4. Host genome degradation
  5. Modification of host RNA polymerase
  6. "Late" viral mRNA Transcription by modified host RNA polymerase
  7. Translation: Synthesis of "late" viral proteins
  8. Viral tail proteins and viral capsid production
  9. Virus assembly
  10. Release and host cell lysis

Temperate Phages (e.g., Bacteriophage λ)

  • Temperate phages make a "molecular decision" to enter either the lytic or lysogenic cycle.
    • Lytic cycle (lysis): Viral DNA is transcribed and replicated, new virus particles are produced, and the host cell is lysed.
    • Lysogenic cycle (lysogeny): Viral DNA is integrated into the host genome, no new virus particles are produced, and most viral genes are turned off.

Lysogeny

  • If lysogeny is established:
    • The host cell becomes "immune" to infection by the same type of phage.
    • Phage in lysogeny is sometimes called a prophage.
    • Active genes within the prophage can confer new properties to the host cell (e.g., non-pathogenic bacteria can produce toxins).

RNA Viruses: Replication Strategies

  • Question: How would an RNA virus replicate its genetic material to produce more virus particles?
  • Nucleic acid-synthesizing enzymes:
    • DNA polymerase: makes DNA.
    • RNA polymerase (and primase): makes RNA.
  • Template usage:
    • DNA polymerase uses a DNA template to make DNA.
    • RNA polymerase and primase use a DNA template to make RNA.
    • These are all DNA-dependent nucleic acid synthesizing enzymes.

RNA-Dependent RNA Polymerase (Replicase)

  • RNA viruses require the ability to synthesize RNA from an RNA template, which cellular hosts do not possess.
  • The viral genome codes for an RNA-dependent RNA-synthesizing enzyme called replicase (or viral replicase, or RdRp, or viral RNAP).
    • Replicase is either synthesized immediately or brought along with the RNA.
  • Retroviruses (e.g., HIV) use a special enzyme called reverse transcriptase to make double-stranded DNA (ds-DNA) from single-stranded RNA (ss-RNA).

Types of RNA Viruses

  • (+) sense strand RNA viruses: RNA can be translated directly, acting as mRNA.
  • (–) sense strand RNA viruses: RNA is complementary and antiparallel to mRNA; it cannot be directly translated.
  • Retroviruses

Rules of Viral Replication

  • You have to leave with what you brought in.
  • If you don’t bring it with you, the cell has to provide it or make it for you.
  • When you make new nucleic acid, what you make is the complement of what you are using as template.
  • Positive-sense RNA molecules are directly translatable.
  • Negative-sense RNA molecules are not directly translatable because they are antiparallel and complementary to positive-sense RNA.

(-) sense RNA vs (+) sense RNA

  • (-) sense RNA requires viral replicase to be translated
  • (+) sense RNA uses the host ribosome to translate directly