Viral Replication Cycle
Viral replication: APUARE โ Attachment, Penetration, Uncoating, Assembly, Release (+ replication inside)
Attachment ยท Penetration ยท Uncoating ยท Replication ยท Assembly ยท Release
Six steps every virus must complete to make new copies of itself
Attachment: viral surface protein binds host receptor (specificity determines tropism). Penetration: endocytosis or membrane fusion. Uncoating: capsid removed, genome released. Replication: DNA/RNA copied using host or viral polymerases. Assembly: new capsids formed. Release: lysis (naked viruses) or budding (enveloped viruses).
► Show full breakdown Attachment
Viral protein binds host receptor โ determines cell tropism
Penetration
Endocytosis or direct membrane fusion
Uncoating
Capsid removed, genome exposed
Replication
Genome and proteins synthesized
Assembly
New virions formed inside cell
Release
Lysis or budding from host membrane
Viral Structure
Virus = nucleic acid + capsid (ยฑ envelope). Naked viruses survive environment better; enveloped are easier to kill.
Viral Structure
What every virus is made of โ and why it matters clinically
Capsid: protein coat protecting nucleic acid. Enveloped viruses (HIV, influenza, herpes): lipid membrane from host cell โ destroyed by soap/alcohol. Naked (non-enveloped) viruses (adenovirus, norovirus, poliovirus): resistant to drying and stomach acid โ fecal-oral transmission.
Baltimore Classification
Baltimore classification: 7 groups by genome type and replication strategy โ "How does the virus make mRNA?"
Baltimore Classification
The universal system for classifying viruses by their genetic strategy
Group I: dsDNA (herpes, adenovirus). Group II: ssDNA (parvoviruses). Group III: dsRNA (rotavirus). Group IV: +ssRNA (poliovirus, hepatitis C). Group V: -ssRNA (influenza, rabies). Group VI: ssRNA retroviruses (HIV). Group VII: dsDNA retroviruses (hepatitis B). Key: +strand RNA = can be directly translated as mRNA.
► Show full breakdown +ssRNA
Acts as mRNA directly โ poliovirus, HCV
-ssRNA
Needs RNA-dep RNA polymerase โ influenza, rabies
Retrovirus
RNA โ DNA via reverse transcriptase โ HIV
HIV Replication
HIV targets CD4+ T cells. RT makes DNA from RNA. Integrase inserts into host genome. Protease matures virions.
HIV Replication Steps
HIV life cycle โ and which step each drug class blocks
HIV binds CD4 + CCR5/CXCR4 coreceptors. Reverse transcriptase (RT) converts RNA โ DNA (error-prone โ mutations โ resistance). Integrase incorporates DNA into host chromosome (latency). Protease cleaves polyproteins into functional components. Drug targets: NRTIs/NNRTIs (RT), integrase inhibitors, protease inhibitors, fusion inhibitors.
Herpesvirus Latency
Herpesviruses: establish latency, reactivate when immunity drops. "Herpes never leaves."
Herpesvirus Latency
Why herpes infections recur throughout life
HSV-1/2: latent in sensory ganglia โ reactivates as cold sores or genital lesions. VZV: primary = chickenpox; latency in dorsal root ganglia; reactivation = shingles (zoster). EBV: latent in B lymphocytes โ reactivates in immunocompromised patients (lymphoma). CMV: latent in myeloid cells โ dangerous in transplant recipients.
Influenza Antigenic Variation
Antigenic drift = point mutations (annual flu). Antigenic shift = gene reassortment (pandemic flu).
Antigenic Drift vs Shift
Why the flu vaccine changes every year โ and how pandemics arise
Influenza A: 18 HA subtypes, 11 NA subtypes (H1N1, H3N2, etc.). Drift: gradual mutations in HA/NA surface proteins โ evades existing antibodies โ seasonal epidemics. Shift: two strains infect same cell, exchange RNA segments โ novel HA/NA combination โ pandemic potential (1918, 2009 H1N1). Only influenza A undergoes shift.
Viral Oncogenesis
Oncogenic viruses: HPV (cervical), EBV (Burkitt's), HBV/HCV (hepatocellular), HTLV-1 (T-cell leukemia)
Cancer-Causing Viruses
Viruses responsible for ~15% of human cancers worldwide
HPV 16/18: E6 degrades p53; E7 inactivates Rb โ cervical, oropharyngeal cancers. EBV: Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma. HBV/HCV: hepatocellular carcinoma via chronic inflammation. HTLV-1: adult T-cell leukemia/lymphoma. Kaposi sarcoma herpesvirus (HHV-8): in AIDS patients.
Interferon Response
Interferons: antiviral cytokines. Type I (IFN-ฮฑ/ฮฒ): block viral replication in neighboring cells.
Innate Antiviral Defense
The body's first-line response to viral infection
Infected cell detects viral dsRNA โ secretes IFN-ฮฑ and IFN-ฮฒ. Neighboring cells: IFN binds receptor โ JAK-STAT pathway โ antiviral state (degrade mRNA, halt translation). IFN-ฮณ (Type II): activates macrophages. Viruses evade IFN: influenza NS1 protein, HPV E6/E7. Recombinant IFN used therapeutically (hepatitis C, MS).
Prions
Prions: misfolded PrP protein โ no nucleic acid. Convert normal PrPc into PrPSc. Fatal, no treatment.
Prion Diseases
Infectious proteins โ not a virus, not a bacterium, but equally deadly
Normal PrPc: ฮฑ-helix rich. Misfolded PrPSc: ฮฒ-sheet rich, insoluble, aggregates in neurons. Causes spongiform encephalopathy. Human diseases: Creutzfeldt-Jakob disease (CJD), kuru (cannibalism), fatal familial insomnia. Animal: scrapie (sheep), BSE/mad cow. Resistant to heat, UV, formalin. No effective treatment.
Lytic vs Lysogenic Cycle
Lytic: virus destroys cell. Lysogenic: virus hides in chromosome. Stress triggers lysogenic โ lytic switch.
Bacteriophage Life Cycles
Two strategies bacteriophages use โ and why lysogeny matters in medicine
Lytic: phage injects DNA โ hijacks cell โ makes copies โ lyses cell. Lysogenic: phage DNA integrates as prophage โ replicates with host. Induction (UV, stress): prophage excises โ lytic cycle. Medical relevance: prophages carry toxin genes (cholera toxin, diphtheria toxin, Shiga toxin) โ lysogenic conversion makes bacteria more virulent.
Antiviral Drug Targets
Antivirals target viral-specific steps: attachment, uncoating, polymerases, proteases, assembly. Spare host cells.
Antiviral Mechanisms
Why antiviral drugs are harder to develop than antibacterial drugs
Viruses use host machinery for most functions โ fewer unique targets. Key antivirals: acyclovir/ganciclovir (herpes thymidine kinase activates โ chain terminator). Oseltamivir/zanamivir (influenza neuraminidase inhibitors โ prevent release). NRTIs/NNRTIs (HIV reverse transcriptase). Protease inhibitors (HIV/HCV). Resistance develops rapidly due to high mutation rates.
Vaccine Types
Vaccine types: Live-attenuated, Killed/inactivated, Subunit, Toxoid, mRNA. "Live Kings Serve Their Masses."
Vaccine Classification
Five vaccine strategies โ each with different strengths and risks
Live-attenuated (MMR, varicella, yellow fever): strong immunity, rare reversion risk โ avoid in immunocompromised. Inactivated (flu shot, IPV, hepatitis A): safe, requires boosters. Subunit (hepatitis B, HPV/Gardasil): just the antigen, very safe. Toxoid (tetanus, diphtheria): inactivated toxin. mRNA (COVID-19): instructs cells to make antigen โ no live virus, rapid production.
► Show full breakdown Live
MMR, varicella, yellow fever โ strong, 1-2 doses
Killed
Flu shot, IPV, hep A โ safe, needs boosters
Subunit
Hep B, HPV โ just protein antigen
Toxoid
Tetanus, diphtheria โ inactivated toxin
mRNA
COVID-19 โ instructs cells to make antigen