Instructor recorded step-by-step videos with animations for synthesis drawings (3 of 5 templates filled).
Reasons for recorded explanations:
Live demo became “wah-wah-wah” after students got lost at Step 2; recordings allow pausing & rewinding.
Use provided template (large rectangle = host cell).
Color code:
One color for RNA, one for DNA, third for proteins.
Solid line = existing strand, dotted = strand under construction.
Label every arrow:
“Transcription” = making any RNA from a nucleic-acid template.
“Translation” = ribosome-mediated protein synthesis using positive-sense RNA.
Note special processes (reverse transcription, RNA-dep-RNA transcription).
Drawings frequently recreated in exam margins; instructor recommends practising on blank paper all weekend.
Normal flow: \text{DNA}\xrightarrow[\text{transcription}]{\text{RNA polymerase}}\text{RNA}\xrightarrow[\text{translation}]{\text{ribosome}}\text{Protein}
Viral exceptions:
RNA viruses: need RNA-dependent RNA polymerase (RdRP) to transcribe RNA → RNA.
Retroviruses: use reverse transcriptase (RNA → DNA) and integrase (viral DNA → host DNA).
Attachment – highly specific ligand–receptor binding (peplomer ↔ receptor).
Penetration
Bacteriophage: “squat-n-squirt” + lysozyme hole in peptidoglycan
Naked virus: direct entry or endocytosis
Enveloped virus: fusion or endocytosis (capsid later uncoated)
Synthesis
Always two goals: replicate genome + make needed proteins.
Genome-type dictates pathway (5 canonical templates: dsDNA, ssDNA, (+)ssRNA, (–)ssRNA, dsRNA).
Enzyme list per type (RdRP, reverse transcriptase, integrase, lysozyme, protease, etc.).
Assembly / Maturation
Capsomeres “self-assemble” around genome.
All enzymes (except bacteriophage lysozyme) packed inside nucleocapsid.
Enveloped viruses: peplomers traffic to host membrane; matrix/tegument may line inner envelope.
Protease cuts multiproteins → functional capsomeres, enzymes, peplomers.
Release
Phages: extra lysozyme dissolves peptidoglycan; cell bursts.
Naked animal viruses: lysis or exocytosis.
Enveloped viruses: budding through membrane containing peplomers; if budding from internal organelle, virions exit via exocytosis.
Synthesis inhibitors
Nucleoside (base) analogs (e.g.
Acyclovir, Valacyclovir = guanine mimics
AZT = thymidine mimic)
Incorporate into growing DNA ⇒ chain termination.
RdRP inhibitors (e.g. Remdesivir, Molnupiravir) — block RNA → RNA extension; used vs. Ebola, COVID-19.
Protease inhibitors (e.g. Paxlovid, Indinavir) — prevent cleavage of multiproteins ⇒ no functional capsid/enzyme.
Release inhibitors (e.g. Tamiflu) — neuraminidase block; virions cannot bud off influenza-infected cell.
Attachment & Penetration – identical to lytic.
Incorporation (NEW Step)
Viral dsDNA integrates into host genome via integrase ⇒ provirus.
If viral genome is not dsDNA, it must first be converted (e.g. reverse transcriptase for RNA viruses, synthesis of complement for ssDNA).
Provirus remains in situ; host replication copies viral genes to all daughter cells.
Trigger / Induction (chemical, physical, hormonal, UV, age, illness, diet [Arg:Lys ratio], etc.)
Synthesis, Assembly, Release – proceed as lytic but using proviral DNA as template.
Latent infection – silent between triggers (e.g. HSV-1/2 cold sores & genital herpes).
Persistent infection – continuous low‐level virion release without killing cell (HIV in CD4 T-cells; ~15 % HSV-2 carriers).
Oncogenic transformation – viral insertion activates oncogene / inactivates tumor suppressor ⇒ cell multiplication (e.g. HPV → cervical cancer, EBV → Burkitt lymphoma).
Integrase inhibitors (e.g. Isentress = Raltegravir) — no provirus formation.
Reverse-transcriptase inhibitors already listed above.
Structure: enveloped; conical capsid; two (+)ssRNA molecules; enzymes = RT, integrase, protease; peplomers gp120/gp41.
Entry: gp120 binds CD4 + co-receptor (CCR5/CXCR4) ⇒ gp41-mediated fusion.
Uncoating ⇒ RT synthesizes RNA/DNA hybrid → dsDNA.
Integrase inserts viral DNA into host chromosome.
Transcription & translation of provirus; protease cleaves multiprotein; assembly at membrane with gp120/41.
Budding & maturation.
Drug intervention points highlighted (attachment antagonists, RTI, INSTI, PI).
Triggers: UV light, stress hormones, emotional trauma, physical trauma (dentist, wrestling), chemical irritants (acidic foods, metal cans), concurrent illness, steroids, aging.
Nutritional influence: high Arginine : Lysine ratio promotes reactivation; raise dietary lysine (milk, cheese, yogurt) and moderate arginine (nuts, chocolate, alcohol).
40 % of frequent-outbreak sufferers can reduce episodes by diet alone.
Whiteboard exercise: groups drew (+)ssRNA lytic synthesis with color code; key takeaways:
Start codon AUG defines positive‐sense strand.
Two-step RNA replication: (+)RNA → (–)RNA (template) → new (+)RNA genomes.
RdRP needed for each RNA→RNA step; protein translated directly from (+)RNA.
Enzyme itself packaged inside virion.
Group case study: Nafamostat shown to block SARS-CoV-2 entry.
Students reasoned it targets attachment/penetration (fusion).
Potential additional drug targets: RdRP, protease, budding (Mpro, PLpro, spike processing by TMPRSS2).
Comparison Chart: fill characteristics of bacteriophage, naked, enveloped viruses across all replication stages; large portion already completed in class.
Draw each synthesis template multiple times from memory; colour & label.
Bring a blank sheet to exam; re-draw pathway in margin to reason through MCQs.
Use active multisensory techniques: speak aloud, teach a peer, record & playback.
Spend ≈ 3\ \text{h}\text{study} : 1\ \text{h}\text{lecture} for summer science course.
Virion genomic copy logic (mirror rule): complement of complement = original.
Central Dogma summarized earlier.
Early HIV era vs. post-protease-inhibitor era: shift from death sentence to chronic manageable disease; socioeconomic impact (credit, insurance).
Stigma & touch: instructor anecdote of guest speaker craving human contact.
Responsible public-health behavior: “Know your status” testing campaigns; asymptomatic transmission during latent/persistent phases.
Integrase, protease, neuraminidase inhibitors demonstrate intersection of molecular biology & drug design.
Capsomere, capsid, nucleocapsid, peplomer, tegument/matrix, RdRP, lysozyme, reverse transcriptase, integrase, protease, provirus, induction, latent vs. persistent infection, oncogene.
[ ] Watch instructor’s three synthesis-drawing videos; complete remaining two templates; submit lytic/lysogenic drawings for bonus.
[ ] Finish Mastering Assignments 3 & 4.
[ ] Update comparison chart before Saturday.
[ ] Prepare for Lecture Test 2 (Topic 3 B only) using old Test 1 virus items for review.
[ ] Practise drawing each genome pathway from scratch; label enzymes, transcription/translation arrows.
[ ] Schedule office-hour consult if unhappy with Test 1 score.
[ ] Balance study time: warn family, plan weekend around lab prep + lecture study.