Viral replication Study Guide

📖 Core Concepts Viral replication: Production of new virus particles inside a host cell; requires entry, genome synthesis, assembly, and release. Host dependence: Viruses need cellular energy, ribosomes, nucleotides, and polymerases; they cannot replicate in non‑living media. DNA vs RNA viruses: DNA viruses generally replicate in the nucleus (except poxviruses) and often use host DNA polymerases. RNA viruses replicate in the cytoplasm and rely on viral RNA‑dependent RNA polymerases (RdRp). Baltimore classification: Groups viruses into 7 classes based on genome type and mRNA synthesis strategy. Lytic vs Lysogenic cycles: Lytic – immediate expression of viral genes → production of virions → cell death. Lysogenic – viral genome integrates into host DNA, replicates silently until induction triggers the lytic phase. 📌 Must Remember Attachment – viral protein ↔ specific host receptor (often mimics normal ligand). Entry routes: Receptor‑mediated endocytosis (most common, no viral energy). Direct envelope‑fusion (creates a pore). Cell‑to‑cell fusion → syncytium formation (low pH). Uncoating – removal of capsid, usually in the compartment where transcription starts (e.g., nucleus for many DNA viruses). Replication strategies by Baltimore class: I: dsDNA → host DNA Pol (nucleus). II: ssDNA → dsDNA intermediate (nucleus). III: dsRNA → viral RdRp in cytoplasm. IV: (+)ssRNA → directly acts as mRNA. V: (‑)ssRNA → viral RdRp makes (+)mRNA. VI: (+)ssRNA → reverse transcriptase → DNA → integration. VII: dsDNA with RNA intermediate → reverse transcription step. Fidelity – DNA virus polymerases have proofreading → lower mutation rate; RNA virus polymerases lack proofreading → high mutagenicity. Therapeutic targets: Reverse‑transcriptase inhibitors → retroviruses & HBV (Class VI & VII). Agents that block entry (receptor antagonists) or release (fusion inhibitors). 🔄 Key Processes Attachment – viral attachment protein binds host receptor → stabilizes virus at plasma membrane. Entry (Penetration) – Endocytosis: receptor binding → clathrin‑mediated vesicle formation → vesicle internalization. Fusion: envelope merges with plasma membrane → genome released to cytosol. Uncoating – capsid disassembly → genome released; often coincides with entry into nucleus (DNA viruses). Replication – DNA viruses: use host DNA Pol (or viral DNA Pol) → produce genome copies. RNA viruses: viral RdRp synthesizes complementary strands; (+)ssRNA → translation; (‑)ssRNA → transcription to (+)mRNA. Retroviruses (Class VI): reverse transcription → DNA → integration. Assembly – capsid proteins + genome combine; location varies (cytoplasm, nucleus, Golgi, membrane). Maturation – proteolytic cleavage or structural rearrangements to become infectious. Release – Budding: acquires lipid envelope from host membrane. Cell lysis: membrane rupture liberates non‑enveloped virions. 🔍 Key Comparisons DNA virus vs RNA virus replication DNA → nucleus (most) & often host DNA Pol; RNA → cytoplasm & viral RdRp. Positive‑sense (+)ssRNA vs Negative‑sense (‑)ssRNA (+)ssRNA = functional mRNA → direct translation. (‑)ssRNA = must be transcribed by viral RdRp to (+)mRNA first. Endocytosis vs Direct Fusion entry Endocytosis: energy‑independent for virus, relies on host signaling. Fusion: envelope viruses fuse at plasma membrane, often pH‑dependent. Lytic vs Lysogenic Lytic: rapid virion production, cell death. Lysogenic: genome integration, silent replication, can be induced. ⚠️ Common Misunderstandings “All RNA viruses replicate in the cytoplasm.” False: Retroviruses (Class VI) reverse‑transcribe to DNA and integrate in the nucleus. “DNA viruses always use host polymerases.” False: Adenoviruses & herpesviruses encode their own DNA polymerases. “Budding always produces enveloped virions.” True, but some non‑enveloped viruses are released by lysis only. “Higher mutation rate = better virus.” High mutagenicity aids adaptation but can also produce non‑viable progeny. 🧠 Mental Models / Intuition “Lock‑and‑key” for attachment – think of viral protein as a key that fits a specific cellular lock (receptor). “Factory floor” analogy – Entry = delivering raw material to the factory; replication = assembly line (DNA vs RNA determines which machines are used). “Two‑track train” for Baltimore classes – One track for DNA → host nucleus; the other for RNA → viral polymerase; the class tells you which track the virus rides. 🚩 Exceptions & Edge Cases Poxviruses (Class I) replicate entirely in the cytoplasm – require their own transcription/replication enzymes. Segmented genomes (Class V) produce separate monocistronic mRNAs for each segment – important for reassortment. Retroviral integration can be latent for years (e.g., HIV reservoirs). 📍 When to Use Which Identify replication site → nucleus = DNA virus (most); cytoplasm = RNA virus or poxvirus. Determine genome polarity → (+)ssRNA → skip transcription step; (‑)ssRNA → need viral RdRp. Therapeutic choice → if virus is retrovirus or HBV → prescribe reverse‑transcriptase inhibitor; if virus buds → consider fusion or protease inhibitors. Diagnostic clues → presence of DNA → likely Class I/II/IV (DNA intermediate) vs RNA → Class III‑VII. 👀 Patterns to Recognize Receptor binding → endocytosis → low‑pH trigger → common for many enveloped viruses (influenza, coronavirus). Polyprotein → proteolytic cleavage → hallmark of many Class IV (+)ssRNA viruses (e.g., picornaviruses). Integration + provirus → retroviral life cycle (Class VI). High mutation rate + antigenic drift → RNA viruses (influenza, HIV). 🗂️ Exam Traps “All DNA viruses replicate in the nucleus.” – Poxviruses are the classic exception. “Negative‑sense RNA viruses are directly infectious.” – They must first be transcribed to (+)RNA; only (+)ssRNA can act as mRNA immediately. “Budding always produces enveloped virions.” – True, but some viruses (e.g., hepatitis B) acquire envelope by a different mechanism (ER/Golgi) not classic plasma‑membrane budding. “Reverse‑transcriptase inhibitors work on all RNA viruses.” – Only those that use a DNA intermediate (Class VI & VII). “Lysogenic cycle = dormant virus.” – The genome is integrated and replicates with host DNA, but can be induced at any time; not permanently dormant. --- Quick Review Tip: Visualize the 7‑step replication cycle (Attachment → Entry → Uncoating → Replication → Assembly → Maturation → Release) and then map each Baltimore class onto the Replication step to instantly recall the required enzymes and cellular compartment. Good luck!