Viral Replication and Bacteriophages — Comprehensive Notes

Viral replication: overview

  • Viruses are obligate intracellular parasites that hijack host cell machinery to replicate.

  • The replication strategy impacts transmission, immune response, and disease.

  • Key terms: viral spikes, capsid, envelope, receptor compatibility, tropism, cytopathic effects (CPE).

  • Replication cycle length varies (e.g., polio: $8\ \text{hours}$, herpes simplex: $36\ \text{hours}$). Some viruses are oncogenic.

  • Bacteriophages infect bacteria and have lytic or lysogenic cycles.

The APUSAR: Steps of viral replication

  • Absorption/Attachment: Virus spikes bind to specific host cell receptors, defining host range and tropism.

  • Penetration: Entry into the host cell via endocytosis or membrane fusion.

  • Uncoating: Viral capsid disassembles, releasing the genome.

  • Synthesis (and replication): Production of viral genomes and proteins.

    • RNA viruses: Replication and translation in cytoplasm; positive-sense RNA acts as mRNA, negative-sense requires RNA-dependent RNA polymerase.

    • DNA viruses: Replication/transcription generally in the nucleus; viral proteins produced in cytoplasm/ER.

    • Retroviruses (e.g., HIV): RNA reverse-transcribed into DNA, integrated into host genome (provirus).

  • Assembly: Viral genomes packaged into capsids; structural proteins assembled; envelopes added for enveloped viruses.

  • Release: Virions exit the cell.

    • Enveloped viruses: Bud from membranes (e.g., plasma, ER, Golgi).

    • Nonenveloped (naked) viruses: Typically released by cell lysis.

Attachment and tropism: how viruses choose their targets

  • Spikes bind to host receptors; this compatibility dictates host range.

  • Tropism: Tissue or organ specificity (e.g., Hepatitis B: liver-tropic).

Entry: how the genome gets into the cell

  • Endocytosis: Virus enters in an endosome.

  • Fusion: Membrane fusion allows direct entry of capsid/genome.

  • Uncoating: Capsid disassembles to release the genome.

Genome replication and translation: RNA vs DNA viruses vs retroviruses

  • RNA viruses: Cytoplasmic replication. Positive RNA acts as mRNA; negative RNA needs RNA-dependent RNA polymerase.

  • DNA viruses: Nuclear transcription/replication. Utilize host or viral polymerases.

  • Retroviruses: RNA $\rightarrow$ DNA (via reverse transcriptase) $\rightarrow$ integration as provirus $\rightarrow$ host transcription/translation.

Life cycle of double-stranded DNA viruses (example: herpesviruses)

  • DNA enters nucleus, early genes transcribed (regulatory proteins), DNA replicates, late genes transcribed (structural proteins), assembly, release.

Enveloped vs nonenveloped viruses: maturation and release

  • Enveloped viruses: Acquire lipid envelope by budding from host membranes (e.g., SARS-CoV-2).

  • Nonenveloped viruses: Released by cell lysis (e.g., poliovirus).

Cytopathic effects (CPE) and tissue damage

  • CPE: Virus-induced host cell damage, altering shape, size, function, or causing death.

  • Inclusion bodies: Accumulations of viral components.

  • Syncytia: Fused multi-nucleated cells.

Persistent infections, latency, and proviruses

  • Persistent infections: Long-term presence in host.

  • Latency: Virus remains in cells with minimal expression; can reactivate (e.g., herpes simplex).

  • Provirus: Viral DNA integrated into host genome (e.g., HIV).

Oncogenic viruses and transformation

  • Oncoviruses (e.g., HPV, HBV) contribute to cancer by disrupting tumor suppressors or activating oncogenes.

  • Roughly $13\%$ of cancers are linked to viral infection.

Bacteriophages: structure, life cycles, and clinical relevance

  • Phages infect bacteria by injecting DNA; do not infect human cells.

  • Lytic cycle: Phage replicates, lyses host cell to release progeny.

  • Lysogenic cycle: Phage DNA (prophage) integrates into bacterial chromosome, replicates with host.

  • Induction: Prophage reactivates to lytic cycle under certain conditions.

  • Lysogenic conversion: Prophages carry toxin genes, conferring new properties to bacteria (e.g., diphtheria toxin).

  • Phage therapy: Highly specific to bacterial strains, offering potential for treating antibiotic-resistant infections.

Key definitions

  • Tropism: Tissue-specific viral affinity.

  • Provirus: Viral DNA integrated into host genome.

  • Syncytia: Fused multi-nucleated cells.

  • CPE: Virus-induced cellular damage.

  • Oncovirus: Virus capable of contributing to cancer.