Genetics of Viruses: Structure, Reproductive Cycles, and Regulation (Chapter 18 Study Notes)

Study Guide - Smart Notes

Tailored notes based on your materials, expanded with key definitions, examples, and context.

Genetics of Viruses

Introduction

Viruses are nonliving particles that possess nucleic acid genomes and require living host cells to reproduce. Their study has been fundamental in understanding genetic material, gene regulation, and molecular biology. This chapter focuses on virus structure, genetic composition, reproductive cycles, and the regulation of viral gene expression, with emphasis on bacteriophage lambda and HIV.

Virus Structure and Genetic Composition

Basic Structure of Viruses

Virion: The complete virus particle, consisting of a nucleic acid genome surrounded by a protein coat called a capsid.
Viral Envelope: Some viruses possess an outer lipid membrane derived from the host cell, called an envelope, which contains viral glycoproteins (spikes).
Bacteriophages: Viruses that infect bacteria, often with complex capsids and accessory structures for host attachment.

Host Range: The spectrum of host species a virus can infect. A host cell is any cell that can be infected by a virus.

Genome Types: Viral genomes can be DNA or RNA, single-stranded or double-stranded, and vary in gene number.

Variations in Virus Structure

Helical Viruses: e.g., Tobacco Mosaic Virus (TMV) – rod-shaped, helical capsid with RNA coiled inside.
Icosahedral Viruses: e.g., Adenovirus – polyhedral capsid with DNA, nonenveloped, with protein fibers.
Enveloped Viruses: e.g., Influenza – polyhedral capsid, RNA genome, surrounded by an envelope with spike glycoproteins.
Complex Viruses: e.g., Lambda phage – head (polyhedral capsid) with DNA, tail fibers, and base plate.

RNA as Genetic Material: The TMV Experiment

Experimental Evidence

Early experiments (Gierer & Schramm; Fraenkel-Conrat & Singer) demonstrated that RNA is the genetic material of TMV.
Reconstitution experiments: Mixing RNA and capsid proteins from different TMV strains showed that the progeny virus phenotype is determined by the RNA, not the protein coat.

Conclusion: The genome of TMV is RNA, which directs the synthesis of new viruses.

Viral Reproductive Cycles

General Steps

Attachment: Virus binds to host cell surface.
Entry: Virus or genome enters host cell.
Integration: (Some viruses) Genome integrates into host genome.
Synthesis of Viral Components: Host machinery synthesizes viral proteins and nucleic acids.
Viral Assembly: Viral components assemble into new virions.
Release: New viruses exit the host cell.

Lytic and Lysogenic Cycles (Bacteriophage Lambda)

Lytic Cycle: Phage DNA directs synthesis of new phages, host DNA is degraded, cell lyses to release progeny.
Lysogenic Cycle: Phage DNA integrates into host chromosome as a prophage, remains latent, and is replicated with host DNA.
Switching: Environmental conditions (e.g., nutrient availability) influence the choice between cycles.

Latency in Viruses

Latency: Virus remains inactive; no new virions are produced.
Lysogeny: Latency in bacteriophages.
Episomes: Some viruses (e.g., herpesviruses) remain latent as extrachromosomal elements.

Emerging Viruses

Definition and Examples

Emerging Viruses: Recently arisen viruses with increased infection potential (e.g., SARS-CoV-2, HIV, new influenza strains).
Coronavirus (SARS-CoV-2): Enveloped, RNA virus causing COVID-19; related to MERS-CoV and SARS-CoV.
HIV: Causes AIDS, damages immune system, increases susceptibility to opportunistic infections.

Regulation of the Bacteriophage Lambda Reproductive Cycle

Lambda Genome Organization

Linear DNA in phage head; circularizes upon entry into host.
Genes organized to reflect lytic and lysogenic cycles.
Key regulatory genes: cI (lambda repressor), cro, cII, cIII, N, Q, integrase (int), excisionase (xis).

Integration into Host Chromosome

Integrase recognizes attP (phage) and attB (bacterial) sites, catalyzing integration of phage DNA into host genome.
Integration forms a prophage flanked by host DNA.

Regulatory Decision: Lytic vs. Lysogenic

Regulated by levels of cII and cro proteins.
cII is degraded by host proteases; high cII (low protease, starvation) favors lysogeny; high cro (high protease, good growth) favors lytic cycle.
cII activates PRE promoter, leading to cI (lambda repressor) synthesis.
cI maintains lysogeny by repressing lytic genes and activating its own expression from PRM promoter.
cro represses PRM and promotes lytic gene expression.

Genetic Switch: The OR Operator

OR region: Contains three operator sites (OR1, OR2, OR3) controlling PR and PRM promoters.
Lambda repressor (cI): Binds OR1 (highest affinity), then OR2 and OR3, turning PR off and PRM on; when OR3 is occupied, PRM is off, reducing cI levels and allowing the cycle to reset.
cro protein: Binds OR3 first, turning PRM off and PR on, promoting lytic cycle.

Induction of the Lytic Cycle

Environmental stress (e.g., UV light) activates RecA protease, which cleaves lambda repressor, allowing cro accumulation and lytic gene expression.

HIV Genetics and Reproductive Cycle

HIV Genome and Structure

Genome: Two copies of single-stranded RNA (~9,749 nucleotides), with nine genes (some as polyproteins).
Key genes:
- gag: Matrix, capsid, nucleocapsid proteins, p6.
- pol: Protease, reverse transcriptase, integrase.
- env: gp41, gp120 (envelope glycoproteins).
- vif, vpu: Infectivity and budding.
- vpr, rev, tat, nef: Regulatory functions.
Structure: RNA genome inside capsid (p24), surrounded by matrix (p17), envelope (host-derived) with gp120/gp41 spikes.

HIV Reproductive Cycle

Attachment: gp120/gp41 bind to host T cell receptors.
Entry: Viral envelope fuses with host membrane; capsid enters cytosol and uncoats.
Reverse Transcription & Integration: Reverse transcriptase synthesizes double-stranded DNA from RNA; integrase inserts DNA into host genome (provirus).
Latency: Provirus may remain inactive for long periods.
Activation: Host transcription factors (e.g., NF-kB) activate provirus transcription upon T cell stimulation.
Synthesis of Viral Components: Three types of HIV RNA are produced:
- Fully spliced: Nef, Tat, Rev proteins.
- Incompletely spliced: Vif, Env, Vpu, Vpr proteins.
- Unspliced: Gag and Gag-pol polyproteins; also serves as viral genome.
Assembly: Gag and Gag-pol polyproteins, viral RNA, and enzymes assemble at plasma membrane; Env proteins are processed and embedded in membrane.
Budding: Immature virion buds from host cell, aided by ESCRT pathway and Vpu (which inhibits tetherin).
Maturation: HIV protease cleaves polyproteins, forming mature virion with organized capsid and functional proteins.

Reverse Transcription (Detailed Steps)

Host tRNA primes DNA synthesis at PBS site.
Reverse transcriptase synthesizes DNA, degrades RNA template (RNase H activity), and completes double-stranded DNA with long terminal repeats (LTRs) at both ends.

Integration into Host Genome

Integrase binds HIV DNA, makes cuts at 3' ends, and with Vpr forms preintegration complex.
Complex enters nucleus, integrase makes staggered cuts in host DNA, and HIV DNA is ligated in; gaps are repaired by host enzymes.

Table: Key Genes and Functions in HIV

Gene	Function
gag	Matrix, capsid, nucleocapsid proteins, p6
pol	Protease, reverse transcriptase, integrase
env	Envelope glycoproteins (gp41, gp120)
vif, vpu	Infectivity, budding
vpr, rev, tat, nef	Regulatory functions

Summary

Viruses have diverse structures and genetic strategies, with genomes of DNA or RNA.
Viral reproductive cycles include lytic, lysogenic, and latent phases, regulated by viral and host factors.
Bacteriophage lambda and HIV serve as key models for understanding gene regulation, integration, and viral assembly.
Emerging viruses pose ongoing challenges due to their adaptability and impact on human health.

Key Equations and Concepts

Integration (site-specific recombination):
Reverse Transcription (simplified):

Additional info: For more detailed molecular mechanisms, refer to primary literature or advanced virology texts.