Lecture 19: Viral Replication

Viral Replication

Introduction

  • Viral replication involves replicating the viral genome, transcribing it into mRNA (for some viruses), and translating the mRNA into viral proteins.
  • After viral entry and uncoating, the nucleic acid is delivered to either the cytoplasm or the nucleus for replication.

Viral vs. Bacterial Growth

  • Bacterial Growth Curve:
    • Lag phase: Bacteria prepare for division.
    • Exponential growth.
  • Viral Growth Curve:
    • Eclipse phase: Active viral replication occurs, but complete viral particles are not yet assembled.
    • Viral nucleic acid is replicated, and viral proteins are synthesized.
    • After enough viral components accumulate, they assemble into complete viral particles (virions), leading to a steep increase.
    • Unlike bacteria, which undergo binary fission, viruses assemble preformed components into virions.

Viral RNA Production

  • Not all viruses produce RNA in the same way.
  • Class 4 (Positive-sense RNA viruses):
    • Their RNA can be directly used as mRNA.
  • Class 6 (Retroviruses like HIV):
    • Their RNA is first converted into DNA.

Viral Genome Replication

  • Viruses use the host cell's machinery for gene replication, transcription, and translation.
  • DNA viruses:
    • DNA replication occurs in the nucleus where DNA polymerase, nucleotides, and other components are located.
    • Transcription of DNA into RNA also occurs in the nucleus, as RNA polymerase is found there.
    • Translation occurs in the cytoplasm due to the presence of ribosomes.
  • Exception: Poxvirus
    • Viral DNA replication occurs in the cytoplasm.

RNA Viruses

  • Cells do not have enzymes that replicate RNA (RNA-dependent RNA polymerase).
  • RNA viruses replicate in the cytoplasm and must have their own RNA replicase (RdRP).
  • Positive-sense RNA can be directly used as mRNA, so no transcription step is needed.
  • Negative-sense RNA must first be converted into positive-sense RNA before translation.
  • Exception: Retroviruses
    • Although RNA viruses, most of their replication occurs in the cytoplasm, but their genome is converted into DNA.

Replication of DNA Viruses

Double-Stranded DNA Viruses
  • DNA is transcribed into RNA using RNA polymerase, and RNA is translated into proteins (structural and nonstructural).
  • DNA polymerase replicates the DNA to produce double-stranded DNA molecules, which assemble with viral proteins.
  • Some viruses encode their own DNA polymerase, while others rely on the host's DNA polymerase.
Single-Stranded DNA Viruses
  • DNA is first converted into double-stranded DNA using host cell DNA polymerase.
  • The double-stranded DNA is then transcribed into mRNA, which is translated into proteins.
  • DNA polymerase replicates the viral genome.
  • Example: Parvovirus (causes slapped cheek syndrome in children).
Double-Stranded DNA Viruses with Gapped DNA
  • One strand is incomplete with a piece of RNA and a protein attached.
  • Host cell DNA polymerase completes the incomplete strand.
  • The RNA and protein are removed, resulting in double-stranded DNA that can be transcribed into mRNA.
  • Reverse transcriptase converts RNA to DNA.
  • Example: Hepatitis B virus.

Replication of RNA Viruses

Positive-Sense RNA Viruses
  • The RNA genome acts as mRNA and is immediately used by ribosomes to produce viral proteins.
  • RNA replicase replicates the positive-sense RNA into negative-sense RNA, which is then used to produce more positive-sense RNA.
  • Examples: Coronaviruses, polioviruses.
Negative-Sense RNA Viruses
  • RNA genome cannot be used as mRNA.
  • The virus carries RNA replicase within the virion.
  • RNA replicase converts the negative-sense RNA to positive-sense RNA, which is used as mRNA.
  • Examples: Measles, mumps, rabies, influenza.
Double-Stranded RNA Viruses
  • Only one family of human viruses: Reoviruses.
  • The genome is segmented.
  • Example: Rotavirus (causes gastroenteritis in children).
  • The genome is transcribed from negative-sense RNA to produce mRNA transcripts within the capsid.
  • mRNA exits the capsid through vertices to be translated into viral proteins.
Retroviruses
  • Positive-sense RNA genome.
  • Must integrate into the host cell genome.
  • Reverse transcriptase converts RNA into double-stranded DNA.
  • Integrase enzyme integrates it into the host cell DNA.
  • The integrated DNA (provirus) is treated as part of the host DNA and transcribed by host cell RNA polymerase.
  • Example: HIV.
  • Drugs that target HIV include integrase inhibitors and reverse transcriptase inhibitors.

General Principles

  • Viruses have different replication strategies based on their genome type.
  • Understanding the genome of a virus is crucial for understanding its replication cycle.