DNA virus Study Guide

📖 Core Concepts DNA Virus – a virus whose genetic material is deoxyribonucleic acid (DNA) and is copied by a DNA‑dependent polymerase. Genome Types Double‑stranded DNA (dsDNA) – two complementary strands; most belong to realms Duplodnaviria or Varidnaviria. Single‑stranded DNA (ssDNA) – one strand; almost all are in realm Monodnaviria (some exceptions). Taxonomic Realms Duplodnaviria: dsDNA, HK97‑fold major capsid protein, often tailed (e.g., Caudovirales). Varidnaviria: dsDNA, jelly‑roll capsid protein, non‑tailed (e.g., adenoviruses, poxviruses). Monodnaviria: ssDNA, HUH‑endonuclease‑driven rolling‑circle replication (CRESS‑DNA). Replication Strategies Bidirectional replication – two forks move outward from an origin. Rolling‑circle replication (RCR) – circular template repeatedly traversed, generating linear concatemeric DNA. Strand‑displacement replication – new strand made, then used as template for its complement. Replicative transposition – integrated viral genome copies itself to a new genomic site. Genome Sense & Packaging Positive‑sense ssDNA = the strand that is packaged; negative‑sense is rare (e.g., Anelloviridae). Reverse‑Transcribing DNA Viruses – DNA genome copied via an RNA intermediate using reverse transcriptase. Cellular Site of Replication Nucleus‑replicating dsDNA viruses rely on host polymerases. Cytoplasmic dsDNA viruses encode their own replication enzymes. --- 📌 Must Remember Realms & Capsid Folds – HK97 fold → Duplodnaviria; jelly‑roll fold → Varidnaviria. ssDNA Realm – Monodnaviria = HUH‑endonuclease + rolling‑circle replication. Key Diseases Herpesviridae (dsDNA) → herpes, chickenpox, shingles, Kaposi’s sarcoma. Papillomaviridae (ssDNA, Monodnaviria) → warts, cervical & other cancers. Poxviridae (dsDNA, Varidnaviria) → smallpox (Variola). Replication Forks – bidirectional replication creates two forks moving opposite directions. RCR Initiation – HUH‑endonuclease nicks the (+) strand, exposing a 3′‑OH for DNA polymerase. Parvovirus RHR – linear ssDNA → hairpin structures → rolling‑hairpin replication. Genome Sense – most ssDNA viruses are positive‑sense; Anelloviridae is the notable negative‑sense exception. Reverse‑Transcribing DNA Viruses use an RNA intermediate, not to be confused with retroviruses (RNA genomes). --- 🔄 Key Processes Bidirectional Replication (dsDNA) Origin of replication is recognized. Two replication forks are assembled. DNA polymerase synthesizes leading strands continuously; lagging strands are synthesized as Okazaki fragments. Rolling‑Circle Replication (RCR) – circular ssDNA HUH‑endonuclease nicks the (+) strand at the origin. 3′‑OH serves as primer; DNA polymerase extends, displacing the old (+) strand. Displaced strand is cleaved and circularized → new ssDNA genome. Strand‑Displacement Replication (dsDNA) Synthesize a new strand using the template strand. The newly made strand becomes the template for synthesis of its complement. Replicative Transposition (dsDNA) Integrated viral genome is excised. Transposase mediates insertion into a new chromosomal location. ssDNA → dsDNA Conversion (Group II viruses) Host DNA polymerase synthesizes the complementary strand after entry. The resulting dsDNA serves as template for transcription → mRNA. Parvovirus Rolling‑Hairpin Replication (RHR) Linear ssDNA forms hairpin ends that act as primers. DNA polymerase extends from hairpins, displacing the opposite strand. New hairpins are generated, allowing continuous replication around the genome. --- 🔍 Key Comparisons dsDNA vs ssDNA Viruses dsDNA: two complementary strands, usually larger genomes, replicate in nucleus or cytoplasm. ssDNA: single strand, often circular, need to synthesize complement before transcription. Duplodnaviria vs Varidnaviria Duplodnaviria: HK97 capsid fold, many are tailed bacteriophages. Varidnaviria: jelly‑roll capsid fold, non‑tailed (adenoviruses, poxviruses). Positive‑sense vs Negative‑sense ssDNA Positive‑sense: packaged strand can be directly transcribed after complement synthesis. Negative‑sense: rare; Anelloviridae packages the opposite strand. Nuclear vs Cytoplasmic Replication (dsDNA) Nuclear: depends on host polymerases, often smaller genomes. Cytoplasmic: encodes its own polymerases and transcription enzymes. Rolling‑Circle vs Rolling‑Hairpin Replication RCR: circular template, continuous linear product; used by most ssDNA viruses. RHR: linear template with hairpin ends; specific to parvoviruses. --- ⚠️ Common Misunderstandings All ssDNA are positive‑sense – false; Anelloviridae are negative‑sense. All dsDNA replicate in the nucleus – false; poxviruses replicate entirely in the cytoplasm. Reverse‑transcribing DNA viruses are retroviruses – they have DNA genomes; retroviruses have RNA genomes. Capsid fold = disease – the fold (HK97 vs jelly‑roll) is a taxonomic marker, not a pathogenic predictor. Rolling‑circle only for plasmids – many ssDNA viruses (e.g., geminiviruses) use the same mechanism. --- 🧠 Mental Models / Intuition Replication Fork as a “Road Fork” – two lanes diverge from a single on‑ramp (origin) and travel outward. Rolling‑Circle = “Tape Recorder” – the circular template is the spool; the polymerase “writes” a continuous tape (linear concatemer) as the spool turns. Capsid Folds as “Origami Patterns” – HK97 = a tightly folded “box” (tailed phages); jelly‑roll = a “flat sheet rolled into a tube” (non‑tailed viruses). Realm as “Family Tree by Core Machinery” – group viruses by the signature enzyme (e.g., HUH‑endonuclease → Monodnaviria). --- 🚩 Exceptions & Edge Cases Anelloviridae – only ssDNA family with circular negative‑sense genomes. Bidnaviruses – can package both strands; do not fit the usual sense rule. Some dsDNA viruses (e.g., certain Monodnaviria members) have dsDNA genomes despite the realm’s ssDNA focus. Reverse‑transcribing DNA viruses – DNA genome but require an RNA intermediate; not classified by the three main realms. Unassigned viruses – many DNA viruses lack a higher taxonomic rank; treat them case‑by‑case. --- 📍 When to Use Which Identify genome type → dsDNA → consider bidirectional, strand‑displacement, or transposition; ssDNA → check for circular vs linear → RCR or RHR. Determine sense → positive‑sense → packaged strand is the (+) strand; negative‑sense → look for Anelloviridae. Choose taxonomic realm HK97 capsid + tailed → Duplodnaviria. Jelly‑roll capsid → Varidnaviria. HUH‑endonuclease gene → Monodnaviria. Predict replication location Virus encodes its own DNA polymerase → likely cytoplasmic replication. No polymerase gene → nucleus‑based replication (uses host enzymes). --- 👀 Patterns to Recognize Circular genome + HUH‑endonuclease → rolling‑circle replication, Monodnaviria. Tailed bacteriophage morphology → HK97 fold → Duplodnaviria. Icosahedral capsid + jelly‑roll fold → Varidnaviria (adenovirus, poxvirus). Linear ssDNA + hairpin ends → rolling‑hairpin replication → parvoviruses. Presence of latency → characteristic of many Duplodnaviria members (herpesviruses). --- 🗂️ Exam Traps “All ssDNA viruses replicate in the nucleus.” – many replicate in the cytoplasm after converting to dsDNA. Confusing capsid folds: a question may list “HK97 fold” and expect you to pick Duplodnaviria, not Varidnaviria. Sense mis‑assignment: a stem‑question may describe a virus with a negative‑sense genome; the correct answer is Anelloviridae, not the generic “ssDNA virus”. Reverse‑transcribing virus vs retrovirus: the former has a DNA genome; retroviruses have RNA genomes. Assuming all dsDNA viruses are large: parvoviruses (small) are dsDNA‑like in replication but belong to Monodnaviria due to their replication enzyme. ---