🧬 Viral architecture & life cycle
Key concept: viruses are obligate intracellular parasites. Their structure determines stability, tropism, and replication strategy.
Naked vs. enveloped
- Naked (non-enveloped): resist detergents, acid, drying; often released by lysis. Examples: adenovirus, parvovirus, papillomavirus.
- Enveloped: fragile; lipid envelope contains viral glycoproteins essential for attachment. Bud from host membranes. Examples: herpesvirus, influenza, HIV.
Genome types
- dsDNA – most DNA viruses (except parvovirus).
- ssDNA – parvovirus B19.
- +ssRNA – can directly serve as mRNA (picornaviruses, flaviviruses).
- −ssRNA – require virion-associated RNA-dependent RNA polymerase.
- dsRNA – reoviruses.
- Retroviruses – +ssRNA with reverse transcriptase.
General replication steps
Attachment→
Entry→
Uncoating→
Macromolecular synthesis→
Assembly→
Release
🔬 High-yield: Enveloped viruses acquire their envelope by budding; naked viruses cause cell lysis. Persistent infections are more common with enveloped viruses (e.g., HBV, HIV).
🩺 Viral hepatitis (A–E)
Hepatitis viruses are hepatotropic but differ in transmission, chronicity, and outcomes.
| Virus | Family / genome | Transmission | Chronic? | Key features |
|---|---|---|---|---|
| HAV | Picornavirus, +ssRNA, naked | Fecal–oral | No | Mild acute; no sequelae. IgM anti-HAV = acute. |
| HBV | Hepadnavirus, dsDNA (partially), enveloped | Parenteral, sexual | 5–10% adults, 90% infants | Cirrhosis, HCC. HBsAg, anti-HBc IgM. |
| HCV | Flavivirus, +ssRNA, enveloped | Parenteral | ~80% | Often subclinical → chronic, HCC. Anti-HCV. |
| HDV | Viroid-like, circular RNA, enveloped (HBsAg) | Parenteral | Co-infection/superinfection | Requires HBV. Severe fulminant. |
| HEV | Hepevirus, +ssRNA, naked | Fecal–oral | Rare (immunocompromised) | Severe in pregnancy (25% mortality). |
🧪 HBV serology: HBsAg positive = acute or chronic infection. Anti-HBc IgM = acute. Anti-HBs = recovery/vaccination. HBeAg = high infectivity.
🧫 DNA viruses – overview
Most are dsDNA, icosahedral, replicate in the nucleus (poxvirus exception: cytoplasm).
| Family | Envelope | Genome | Replication site | Clinically relevant |
|---|---|---|---|---|
| Parvoviridae | Naked | ssDNA | Nucleus | B19 (fifth disease, aplastic crisis) |
| Papillomaviridae | Naked | dsDNA circular | Nucleus | HPV (warts, cervical cancer) |
| Polyomaviridae | Naked | dsDNA circular | Nucleus | BK, JC (PML) |
| Adenoviridae | Naked | dsDNA linear | Nucleus | ARD, conjunctivitis, gastroenteritis |
| Hepadnaviridae | Enveloped | dsDNA (partial) | Nucleus (RNA intermediate) | HBV |
| Herpesviridae | Enveloped | dsDNA | Nucleus | HSV, VZV, EBV, CMV, HHV-6, HHV-8 |
| Poxviridae | Enveloped | dsDNA | Cytoplasm | Variola, molluscum, monkeypox |
▶ Parvovirus B19
- Disease: Fifth disease (erythema infectiosum) – “slapped cheek” rash in children; aplastic crisis in sickle cell; hydrops fetalis.
- Pathogenesis: targets erythroid progenitors.
▶ HPV (Papillomaviridae)
- Types 6,11 – genital warts (benign).
- Types 16,18 – cervical, anal, oropharyngeal cancer. E6/E7 inactivate p53/Rb.
- Diagnosis: koiocytes on Pap smear.
🦠 Herpesviridae (8 human types)
Large dsDNA, enveloped, establish latency, reactivation.
HSV-1 & HSV-2
- HSV-1: oral cold sores, keratitis, encephalitis (temporal lobe). Latent in trigeminal ganglion.
- HSV-2: genital herpes, neonatal herpes. Latent in sacral ganglia.
- Treatment: acyclovir (requires viral thymidine kinase).
VZV
- Primary = chickenpox (asynchronous rash). Reactivation = shingles (dermatomal).
- Latent in dorsal root ganglia.
EBV
- Infectious mononucleosis: fever, pharyngitis, lymphadenopathy, splenomegaly.
- Heterophile-positive (Monospot). Atypical lymphocytes (Downey cells).
- Associated with Burkitt lymphoma, nasopharyngeal carcinoma.
CMV
- Heterophile-negative mononucleosis. Congenital infection: jaundice, petechiae, “blueberry muffin” baby.
- Owl-eye inclusions. Retinitis in AIDS.
HHV-6 / HHV-8
- HHV-6: roseola (exanthem subitum) – fever then rash.
- HHV-8: Kaposi sarcoma (AIDS-related).
📌 Poxviridae & other DNA viruses
Smallpox (variola): eradicated; synchronous rash, same stage. Guarnieri bodies (cytoplasmic).
Molluscum contagiosum: umbilicated warts; eosinophilic inclusion bodies.
Molluscum contagiosum: umbilicated warts; eosinophilic inclusion bodies.
Monkeypox (2022 outbreak)
- Transmission: respiratory, direct contact. Rash, lymphadenopathy.
- Highest risk: men who have sex with men (during outbreak).
💊 Antiviral drugs – mechanisms
| Stage | Drug example | Target / mechanism | Virus |
|---|---|---|---|
| Attachment | Maraviroc | CCR5 antagonist | HIV |
| Penetration | Enfuvirtide | Fusion inhibitor | HIV |
| Uncoating | Amantadine | M2 blocker (influenza A) | Influenza |
| Nucleic acid synthesis | Acyclovir, zidovudine | DNA polymerase / RT inhibition | HSV, HIV |
| Protease | Ritonavir | Protease inhibitor | HIV |
| Integrase | Raltegravir | Integrase inhibitor | HIV |
| Release | Oseltamivir | Neuraminidase inhibitor | Influenza |
📌 Exam pearl: Acyclovir requires viral thymidine kinase for activation; resistance often due to TK mutations.
🧪 RNA viruses – general features
- Most are enveloped (exceptions: picornavirus, calicivirus, hepevirus, reovirus).
- Segmented genomes: orthomyxovirus, bunyavirus, arenavirus, reovirus.
- −ssRNA viruses carry RNA-dependent RNA polymerase in the virion.
+ssRNA → directly translated (e.g., poliovirus, HCV).
−ssRNA → requires polymerase to make mRNA (e.g., influenza, rabies).
Retroviruses → reverse transcriptase (RNA → DNA).
−ssRNA → requires polymerase to make mRNA (e.g., influenza, rabies).
Retroviruses → reverse transcriptase (RNA → DNA).
⚡ Clinical pearls & high-yield
- Encephalitis: HSV-1 is the most common cause of sporadic viral encephalitis in the U.S. (temporal lobe involvement).
- Mononucleosis: heterophile-positive = EBV; heterophile-negative = CMV.
- Immunocompromised: CMV retinitis, HHV-8 Kaposi, JC virus PML.
- Hepatitis B: window period = HBsAg disappears, anti-HBs not yet detectable; anti-HBc IgM positive.
- HPV vaccine: Gardasil 9 covers types 6,11,16,18,31,33,45,52,58.
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