14.3 Viruses and Prions
Key Takeaways
- Enveloped viruses are disrupted by detergents and drying; naked viruses survive the GI tract and fomites and must lyse cells to exit. Negative-sense RNA viruses carry an RNA-dependent RNA polymerase in the virion.
- Herpesviruses are enveloped dsDNA agents that establish latency (HSV in sensory ganglia, VZV in dorsal root ganglia, EBV in B cells, CMV in monocytes). Reactivated VZV follows a dermatome as zoster.
- Influenza antigenic drift is HA/NA point mutation; antigenic shift is reassortment of segmented RNA between strains and can create pandemic genomes. HBV is the DNA hepatitis virus; HAV/HCV/HEV are RNA.
- Prions are misfolded PrPSc that template conversion of PrPC; they contain no nucleic acid, survive standard autoclaving and formalin, and cause CJD, vCJD/BSE, kuru, FFI, and GSS.
- Vertical and sexual transmission mark HSV, HBV, HIV, and HPV; fecal–oral marks HAV, HEV, polio, rotavirus, and norovirus; respiratory droplets or nuclei mark influenza, measles, VZV, and SARS-like coronaviruses.
Viruses and prions: the third 18% Microbiology topic
Quick Answer: DNA or RNA, never both. Envelope from host membrane, or naked capsid. Live-cell parasites. Herpes = latency. Orthomyxovirus = segmented, drift versus shift. HBV = DNA hepatitis virus. Prion = PrPSc, no genome, protease-resistant, CJD/BSE.
Structure and biochemical characteristics
A virion is nucleic acid plus a capsid (protein coat assembled from capsomers), with or without a lipid envelope studded with glycoproteins. Viruses have DNA or RNA, not both. They are obligate intracellular; they have no 70S ribosomes and no ATP-generating machinery. Size is typically 20–300 nm—below light-microscope resolution except poxvirus inclusion factories.
| Feature | Teaching rule |
|---|---|
| Naked capsid | Environmentally stable; fecal–oral possible; exit by lysis; antibody neutralization is relatively effective |
| Enveloped | Fragile to detergent, ether, drying, bile, acid; transmission often respiratory droplets, blood, sex, or saliva; exit by budding; neutralizing antibody targets envelope glycoproteins |
| Icosahedral capsid | Most DNA viruses; many RNA viruses |
| Helical capsid | Most mammalian helical viruses are enveloped (exception teaching: naked helical plant viruses are not the human exam set) |
| Complex | Poxviruses (brick-shaped, replicate in cytoplasm) |
DNA viruses (mnemonic families): herpes, hepadna, adeno, papova/papilloma/polyoma, parvo, pox. Almost all DNA viruses are double-stranded and icosahedral and replicate in the nucleus. Exceptions: parvovirus is ssDNA; poxvirus is dsDNA but replicates in the cytoplasm (brings its own DNA-dependent RNA polymerase). Hepadnavirus (HBV) is partially dsDNA and uses reverse transcriptase in its life cycle even though the infectious genome is DNA.
RNA viruses are mostly single-stranded. Positive-sense RNA can serve as mRNA (picornavirus, flavivirus, togavirus, calicivirus, coronavirus). Negative-sense RNA must carry RNA-dependent RNA polymerase in the virion (orthomyxo, paramyxo, rhabdo, filo, bunya, arena). Double-stranded RNA: reovirus/rotavirus (also segmented). Retroviruses are +ssRNA that reverse-transcribe to DNA and integrate.
Segmented genomes (reassortment risk): orthomyxovirus (8 influenza A/B segments), reovirus (11), bunyavirus (3), arenavirus (2). Antigenic drift is polymerase error (point mutations in HA/NA). Antigenic shift is reassortment when two influenza A viruses co-infect a cell (classically swine or human cell with avian and human strains)—the structural reason pandemics happen. Paramyxoviruses are not segmented; measles does not shift.
Resistance. Naked viruses (adeno, parvo, papova, picorna, calici, reo) persist on fomites and in stool. Enveloped viruses die on dry surfaces faster. Alcohol gels disrupt envelopes; they are weaker against some naked viruses (norovirus is the infection-control celebrity). Prions are not viruses and shrug at UV, formalin, and routine autoclaving—see the prion section.
Replication and pathogenicity
Generic cycle: attachment (receptor tropism) → entry (fusion for many envelopes; endocytosis) → uncoating → gene expression and genome replication → assembly → release (bud or lyse). Tropism is receptor geography: HIV gp120 binds CD4 plus CCR5 or CXCR4; EBV gp350 binds CD21 (CR2) on B cells; influenza HA binds sialic acid; rabies glycoprotein binds nicotinic ACh receptors at the NMJ then travels retroaxonal to CNS; parvovirus B19 binds P antigen on erythroid precursors; SARS-like coronaviruses use ACE2.
Pathogenicity mechanisms:
| Mechanism | Example |
|---|---|
| Cytolytic replication | Poliovirus motor neurons; influenza respiratory epithelium |
| Inhibition of host macromolecules | Poliovirus protease cleaves eIF4G; many viruses shut off MHC |
| Syncytia | Paramyxoviruses, HSV, HIV (fusion proteins) |
| Inclusion bodies | Negri (rabies cytoplasmic); Cowdry (HSV nuclear); owl-eye (CMV nuclear) |
| Latency / reactivation | Herpes family |
| Oncogenesis | HPV E6/E7 vs p53/Rb; HBV/HCV → HCC; EBV → Burkitt, nasopharyngeal carcinoma, some Hodgkin; HTLV-1 → ATLL; HHV-8 → Kaposi |
| Immune-mediated injury | HBV cytotoxic T cells kill hepatocytes; influenza cytokine storm; dengue second-infection enhancement |
| Antigenic variation | Influenza drift/shift; HIV reverse-transcriptase error |
Genetics. RNA viruses mutate fast (no proofreading except coronavirus exonuclease). DNA viruses are more stable. Recombination can occur in DNA viruses and in some RNA viruses; reassortment is the segmented-RNA special. Phenotypic mixing is a coat from one virus wrapping the genome of another in a co-infected cell—next generation reverts. Complementation is one mutant supplying a protein another mutant lacks.
Interferons α and β from infected cells induce an antiviral state (protein kinase R, RNase L). That is host pathogenicity control, not a virus structure fact, but stems love “first cytokine of a viral infection.” NK cells kill MHC I–downregulated targets (Immunology). CD8 cells clear most acute viral infections; antibody matters more for preventing entry and for free virus in blood.
Major human viruses by family (communicable diseases)
Herpesviruses (enveloped dsDNA, nuclear replication, latency):
| Virus | Latency site | Disease |
|---|---|---|
| HSV-1 | Trigeminal ganglion | Oral vesicles, temporal-lobe encephalitis, keratoconjunctivitis |
| HSV-2 | Sacral ganglia | Genital vesicles, neonatal herpes |
| VZV | Dorsal root / cranial sensory ganglia | Chickenpox then dermatomal zoster; pneumonia in adults |
| EBV | Memory B cells | Mononucleosis (heterophile+), oral hairy leukoplakia, listed cancers |
| CMV | Monocytes | Heterophile− mono; congenital blueberry-muffin, hearing loss; retinitis in AIDS |
| HHV-6 | T cells / various | Roseola (sixth disease), high fever then rash |
| HHV-8 | B cells / endothelium | Kaposi sarcoma |
Tzanck smear multinucleated giant cells: HSV and VZV, not CMV. Acyclovir requires viral thymidine kinase—structure/pathogenicity, not a prescription pad.
Other DNA viruses: Adenovirus (naked dsDNA)—pharyngoconjunctival fever, epidemic keratoconjunctivitis, hemorrhagic cystitis, dense nuclear inclusions. HPV (naked dsDNA)—skin warts (1, 2, 4), genital warts (6, 11), cervical/anal/oropharyngeal cancer (16, 18); E6/E7. JC virus (polyoma)—PML in immunocompromised. BK virus—transplant nephropathy. Parvovirus B19 (naked ssDNA)—slapped-cheek fifth disease, aplastic crisis in sickle cell, hydrops fetalis, adult arthralgia. Poxviruses (enveloped, cytoplasmic)—smallpox (eradicated), molluscum contagiosum. HBV is tabulated with hepatitis below.
Picornaviruses (naked +ssRNA): polio, coxsackie A (herpangina, hand-foot-mouth) and B (myocarditis, pleurodynia), echovirus (aseptic meningitis), rhinovirus (acid-labile, not fecal–oral), HAV. Calicivirus: norovirus—cruise-ship vomiting, extremely low infectious dose, naked, fomites. Reovirus: rotavirus—winter infant diarrhea, villous blunting, segmented dsRNA. Togavirus: rubella (German measles, congenital triad) and alphaviruses (EEE, WEE, Chikungunya). Flavivirus: HCV, yellow fever, dengue, West Nile, Zika. Coronavirus: common cold plus epidemic zoonotic strains using ACE2. Orthomyxovirus: influenza A/B; M2 ion channel (A); HA cleavage tropism. Paramyxovirus: measles (Koplik, cough-coryza-conjunctivitis, SSPE, giant-cell pneumonia), mumps (parotitis, orchitis, meningitis), RSV (bronchiolitis), parainfluenza (croup). Rhabdovirus: rabies, bullet-shaped, Negri bodies, bat/skunk/raccoon reservoirs in the United States. Filovirus: Ebola/Marburg hemorrhagic fever. Bunyavirus: hantavirus (rodent urine, pulmonary syndrome), California encephalitis. Arenavirus: LCMV, Lassa (rodent). Retrovirus: HIV (AIDS), HTLV-1 (ATLL, HAM/TSP).
Hepatitis comparison (always a table):
| Virus | Genome | Envelope | Transmission | Chronicity | Notes |
|---|---|---|---|---|---|
| HAV | +ssRNA picorna | Naked | Fecal–oral | No | IgM anti-HAV acute; vaccine is killed |
| HBV | Partial dsDNA hepadna | Enveloped | Blood, sex, vertical | Yes | Reverse transcriptase; HBsAg; HCC; subunit vaccine |
| HCV | +ssRNA flavi | Enveloped | Blood | High | No vaccine; HCC; cryoglobulins |
| HDV | Circular ssRNA delta | Uses HBsAg envelope | Parenteral | With HBV | Defective; co- or superinfection |
| HEV | +ssRNA hepe | Naked | Fecal–oral | No (except immunocompromised) | Fulminant in pregnancy |
HIV (review of structure, not the AIDS opportunistic catalog): +ssRNA dimer, envelope gp120/gp41, capsid p24, enzymes reverse transcriptase, integrase, protease. Tropism switch CCR5 → CXCR4. Serology window versus p24/NAAT was Immunology. HTLV-1 is the other human retrovirus to name.
Oncogenic set worth repeating in one line: HPV, HBV, HCV, EBV, HHV-8, HTLV-1, Merkel cell polyomavirus. Not influenza, not rhinovirus.
Prion diseases
Prions are infectious proteins without nucleic acid. Cellular PrPC is a normal GPI-anchored neuronal glycoprotein, protease-sensitive, α-helix-rich. Pathogenic PrPSc is β-sheet-rich, partially protease-resistant, and templates conversion of PrPC to more PrPSc. The gene is PRNP on chromosome 20; familial diseases are PRNP mutations, but the infectivity is still the misfolded conformer. There is no inflammation, no interferon response, and no antibody that clears it. Histology is spongiform change, neuronal loss, and sometimes amyloid plaques (especially vCJD and kuru).
| Disease | Host / source | Distinguishing teaching point |
|---|---|---|
| Sporadic CJD | Human, no identified exposure | Most common human prion disease; rapidly progressive dementia, startle myoclonus, periodic sharp waves; weeks to months |
| Familial CJD / GSS | PRNP germline | GSS is slower, with prominent cerebellar ataxia and PrP plaques |
| Fatal familial insomnia | PRNP (typically codon 178 with 129 context) | Thalamic degeneration, severe insomnia |
| Iatrogenic CJD | Contaminated neurosurgical instruments, cadaveric dura, cadaveric GH | Prions survive routine sterilization |
| Kuru | Ritual endocannibalism (Fore people, historical) | Cerebellar ataxia; human-to-human oral/neural tissue |
| Variant CJD | BSE (cattle) food chain | Younger patients, psychiatric prodrome, florid plaques; lymphoid tissue (tonsil) may be positive |
| BSE | Cattle; likely scrapie-contaminated feed historically | Mad cow; zoonotic to vCJD |
| Scrapie | Sheep and goats | Not shown to infect humans in the same way as BSE |
| CWD | Cervids | Chronic wasting disease; zoonotic risk remains a surveillance issue—do not invent a 2026 case-count |
Resistance. Prion infectivity survives boiling, alcohol, formalin, UV, and standard autoclave cycles used for bacteria. Inactivation teaching uses prolonged autoclaving at higher temperature/NaOH or dedicated protocols for neurosurgical instruments—details of hospital policy are epidemiology; the exam fact is extreme resistance because there is no nucleic acid to denature and the β-sheet aggregate is hardy. Do not call a prion a viroid (plant RNA pathogen) or a defective virus (HDV is the defective virus).
Pathogenicity is gain-of-structure: conversion, aggregation, synaptic loss. Genetics of susceptibility includes PRNP codon 129 Met/Val polymorphism (homozygosity over-represented in sporadic and iatrogenic CJD). Antigenicity is poor; hosts do not mount a protective prion-specific immune response, which is why serology does not diagnose CJD the way ELISA diagnoses hepatitis. Diagnosis teaching is EEG, CSF 14-3-3 or RT-QuIC, MRI, and neuropathology—not IgM titers.
Spongiform encephalopathy is also listed among CNS degenerative infections in Pathology nervous-system disease (/study-guides/nbce-part1/pathology-systems/nervous-system-disorders); here the scored object is the agent: protein-only, transmissible, species-adapted (BSE vs scrapie vs CWD).
Reservoirs and modes of transmission
| Route | Viruses / prions to attach |
|---|---|
| Respiratory droplets | Influenza, RSV, measles, mumps, rubella, adenovirus, SARS-like coronavirus |
| Airborne nuclei | Measles, VZV, smallpox (historical); TB is bacterial |
| Fecal–oral | HAV, HEV, polio, coxsackie, rotavirus, norovirus, adenovirus 40/41 |
| Direct contact / fomites | HSV, adenovirus conjunctivitis, norovirus, molluscum |
| Sexual | HSV-2, HPV, HBV, HIV |
| Blood / percutaneous | HBV, HCV, HDV, HIV, HTLV |
| Vertical | HSV, CMV, rubella, VZV, parvovirus B19, HIV, HBV, Zika |
| Arthropod | Flavivirus and togavirus arboviruses; bunyavirus; not hepatitis A |
| Animal bite / saliva | Rabies |
| Rodent excreta | Hantavirus, arenaviruses |
| Bird | West Nile (mosquito bridge); influenza A mixing in birds/swine |
| Neural tissue / food-chain prion | Kuru, iatrogenic CJD, vCJD/BSE |
Reservoir notes. Humans are the only reservoir for measles, polio, smallpox (eradicated), and HAV. Zoonoses: rabies (mammals), influenza A (birds/swine), Ebola (bats suspected), MERS (camels), SARS-origin bat coronaviruses, BSE (cattle). Latency reservoirs are the ganglia and B cells listed under herpes—reactivation is not a new external exposure. Seasonality is a transmission clue: rotavirus winter, enterovirus summer, influenza winter in temperate zones.
Prevention links without stealing the epidemiology chapter: live MMR and varicella, killed HAV and injected influenza, recombinant HBV and HPV, inactivated polio, rabies vaccine plus immunoglobulin after exposure, oseltamivir as a neuraminidase fact (HA/NA structure), acyclovir as a herpes thymidine-kinase fact. Prion disease has no vaccine and no serology; prevention is food-chain control and instrument protocols.
Viruses-and-prions items reward a two-step answer: first DNA versus RNA and envelope versus naked, then the named family disease and the route. If the stem has rapidly progressive dementia without fever or antibody, switch from virus to PrPSc.
Creutzfeldt–Jakob disease is transmitted by which kind of agent?
Pandemic influenza A strains arise most directly from which genetic process?
Which hepatitis virus has a partially double-stranded DNA genome, encodes a reverse transcriptase, and is prevented by a recombinant surface-antigen vaccine?