Viral Replication

Viral Replication Steps - The Great Hijack

• Attachment: Virus binds specific host cell receptors.
• Penetration: Entry by endocytosis or membrane fusion.
• Uncoating: Viral genome released from capsid.
• Synthesis: Host machinery hijacked for viral replication & protein production.
• Assembly: New virions self-assemble.
• Release: Exit by lysis or budding. 📌 APUSAR

⭐ Eclipse phase: Post-uncoating, pre-assembly; no infectious virus detectable during this period as the virus has disassembled to replicate its components internally within the host cell before new complete virions are formed and released.

Attachment & Entry - Crashing the Gates

• Attachment (Adsorption): Specific Viral Attachment Protein (VAP)-receptor binding.
  • VAPs bind host cell surface receptors (proteins, carbohydrates).
  • Examples: HIV gp120 ➔ CD4; Influenza HA ➔ Sialic acid.
• Entry & Uncoating: Virus penetrates cell; capsid removed.
  • Fusion: Enveloped viruses (e.g., HIV) merge viral envelope with cell membrane.
  • Endocytosis: Common for enveloped (e.g., Influenza) & naked viruses.
  • Translocation: Rare; direct genome passage (e.g., Poliovirus).
  • Uncoating releases viral genome into cytoplasm.

⭐ HIV entry requires the CD4 receptor and a co-receptor (CCR5 or CXCR4).

Uncoating - Genome Unleashed

• Viral capsid breaks down, releasing the viral genome (RNA/DNA) into the host cell.
• Mechanisms vary:
  • Fusion with cell membrane (e.g., HIV).
  • Endocytosis followed by pH-dependent uncoating in endosomes (e.g., Influenza).
  • Direct penetration/injection.
• Site: Cytoplasm (most RNA viruses); Nucleus (most DNA viruses, Influenza, Retroviruses).

⭐ Influenza virus uncoating within the endosome is critically dependent on the M2 protein, an ion channel that allows proton influx, acidifying the virion interior. This is a target for antiviral drugs like Amantadine and Rimantadine (though resistance is common).

Biosynthesis - Viral Factory Frenzy

• Viruses hijack host cell machinery for replication: ribosomes, enzymes, nucleotides.
• Baltimore Classification framework: Guides understanding of mRNA synthesis & genome replication pathways for diverse viral types (I-VII).
• Core Processes (Temporal Regulation):
  • Early Transcription/Translation: Produces non-structural proteins (e.g., polymerases, immune modulators).
  • Genome Replication: Amplifies viral genetic material.
  • Late Transcription/Translation: Produces structural proteins for virion assembly.
• Site of Synthesis:
  • Most DNA viruses: Nucleus (e.g., Herpes, Adeno). 📌 Exception: Poxviruses (cytoplasm).
  • Most RNA viruses: Cytoplasm (e.g., Polio, Measles). 📌 Exceptions: Influenza, Retroviruses (nuclear phase).
• Key Viral Enzymes (often targets for antivirals):
  • RNA-dependent RNA polymerase (RdRp): Essential for most RNA viruses (e.g., HCV, Influenza).
  • Reverse Transcriptase (RT): Hallmark of Retroviruses (e.g., HIV); converts viral RNA to DNA.
• Viroplasms / Viral Factories: Specialized, often membrane-bound, cytoplasmic sites for efficient viral replication and assembly, concentrating components.

⭐ Poxviruses (e.g., Smallpox, Molluscum contagiosum) are unique DNA viruses that replicate entirely in the cytoplasm, bringing their own DNA-dependent RNA polymerase.

Assembly & Release - The Great Escape

• Assembly: Viral genome & proteins assemble.
  • Site: Nucleus (Herpes, Adeno) or Cytoplasm (Pox, Picorna).
  • Capsid encloses genome.
• Release Mechanisms:
  • Lysis: Non-enveloped viruses (e.g., Adeno) burst cell.
  • Budding: Enveloped viruses (e.g., HIV, Flu) acquire host membrane.
    • From plasma, nuclear, ER, Golgi membranes.
    • Influenza neuraminidase aids. 📌 NA cuts Anchor!
  • Exocytosis (some).

⭐ Many enveloped viruses (e.g., HIV, Influenza) bud from plasma membrane; Herpesviruses from nuclear membrane.

High‑Yield Points - ⚡ Biggest Takeaways

• Viral replication involves attachment, penetration, uncoating, biosynthesis, assembly, and release.
• Most DNA viruses replicate in the nucleus (exception: Poxviruses in cytoplasm).
• Most RNA viruses replicate in the cytoplasm (exceptions: Influenza virus, Retroviruses in nucleus).
• The eclipse period is when no infectious virions are detectable intracellularly.
• Enveloped viruses are typically released by budding; non-enveloped viruses often cause cell lysis.
• Reverse transcriptase (RNA-dependent DNA polymerase) is unique to Retroviruses.
• Latency, a dormant state, is characteristic of viruses like Herpesviruses and HIV (Retrovirus).