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