🧬 Virion Structure
Building blocks
- Nucleic acid core
- DNA or RNA
- Never both in one virion
- Capsid
- Protein shell built from repeating capsomers
- Protects the genome
- Nucleocapsid = genome + capsid
- Some carry packaged enzymes (e.g., polymerases)
Naked virion
Genome+Capsid=Nucleocapsid (no envelope)
Enveloped virion
Nucleocapsid+Host-derived lipid bilayer with viral glycoproteins
- Glycoproteins on the envelope drive attachment
- Glycoproteins are required for infectivity
Capsid symmetry
- Icosahedral most common
- Can be naked or enveloped
- Helical
- Always found inside an envelope
- No naked helical human viruses
- Poxviruses
- Complex, brick-shaped morphology
RNA polarity
| Type | Meaning |
|---|---|
| Positive-sense (+) |
|
| Negative-sense (−) |
|
High-yield
- Naked viruses survive heat, detergents, acid and solvents.
- Enveloped viruses are inactivated by these because the lipid layer is disrupted.
- Disrupting the envelope destroys the glycoproteins needed to attach to cells.
🔁 Replication Cycle and Antivirals
Generalized sequence
1 Attachment→2 Penetration→3 Uncoating→4 Synthesis→5 Protein processing→6 Assembly→7 Release
Macromolecular synthesis phases
- Early phase
- Makes enzymes and regulatory proteins
- Shuts down host synthesis
- Supplies replication machinery if the virus lacks it
- Genome replication
- Late phase
- Makes structural proteins
Drugs mapped to the step they block
| Step | Drug | Mechanism | Used for |
|---|---|---|---|
| Attachment | Maraviroc | CCR5 antagonist | HIV |
| Penetration | Enfuvirtide | Fusion inhibitor | HIV |
| Uncoating | Amantadine, rimantadine | Block M2 ion channel | Influenza A (obsolete) |
| Nucleic acid synthesis | Acyclovir, zidovudine, many others | Chain-terminating or polymerase-inhibiting analogs | Largest antiviral class |
| Protein processing | Ritonavir | Protease inhibitor | HIV |
| Assembly | None | None | None |
| Release | Oseltamivir | Neuraminidase inhibitor | Influenza |
| Integration (retrovirus only) | Raltegravir | Integrase inhibitor | HIV |
Exam trap
- Oseltamivir acts at release, not at entry.
🎯 Tropism, Entry, Genomes and Infection Patterns
Attachment and tropism
- Enveloped virus uses envelope glycoproteins
- Naked virus uses capsid surface proteins
- Receptor distribution sets host range
- Receptor distribution sets tissue specificity
Key receptors
| Virus | Target | Receptor |
|---|---|---|
| HIV | Helper T cells, macrophages, microglia | CD4 plus CCR5 or CXCR4 |
| EBV | B cells | CD21 (CR2) |
| Rabies | Neurons | Acetylcholine receptor |
| Rhinovirus | Respiratory epithelium | ICAM-1 |
Entry routes
- Receptor-mediated endocytosis
- Coated-pit uptake
- Membrane fusion (enveloped viruses with fusion proteins)
Arboviruses
- Spread by arthropod vectors
- Mosquitoes are the most frequent vector
- Ticks, midges, sandflies are less common
- Alphaviruses (togavirus encephalitis group)
- Flaviviruses
- Bunyaviruses
Genome replication strategies
| Virus | Genome | Intermediate | Progeny |
|---|---|---|---|
| Most dsDNA | dsDNA | None | dsDNA |
| Hepatitis B | Partial dsDNA | RNA | dsDNA |
| Most (+)ssRNA | (+)RNA | (−)RNA | (+)RNA |
| Retrovirus | (+)RNA | dsDNA | (+)RNA |
| (−)ssRNA | (−)RNA | (+)RNA | (−)RNA |
- All ssRNA viruses replicate through a complementary intermediate
- Reverse transcription in retroviruses
- Enzyme: reverse transcriptase
- Makes a DNA strand from RNA, then degrades the RNA, then copies the DNA strand
- Hepatitis B uses its DNA polymerase with reverse transcriptase activity
Release
- Naked virus
- Exits by lysing the cell
- Only lytic or latent infections, never persistent productive
- Enveloped virus
- Exits by budding
- Cell may survive and shed low-level virus for years (chronic hepatitis B)
Time courses of infection
| Pattern | Behavior | Example |
|---|---|---|
| Acute | Virus rises, disease, then clearance | Smallpox |
| Acute with rare late complication | Intact virus gone, defective virus persists in brain years later | Measles → subacute sclerosing panencephalitis |
| Latent | Silent phase with limited viral proteins, later reactivation | Varicella-zoster: chickenpox, then shingles |
| Chronic productive | Continuous shedding | Hepatitis B |
Typical age at infection
- Congenital: CMV, rubella, HSV-2, HIV, B19
- Perinatal: hepatitis B, HSV-2, HIV
- Infants: RSV (bronchiolitis), parainfluenza (croup), rotavirus (diarrhea)
- Children: measles, mumps, hepatitis A, varicella, norovirus, rubella, B19
- Older adults: zoster, West Nile and St. Louis encephalitis
🩸 Viral Hepatitis
Common symptoms
- Fever, malaise, headache
- Anorexia, vomiting
- Dark urine, jaundice
Comparison of hepatotropic viruses
| Feature | A | B | C | D | E |
|---|---|---|---|---|---|
| Family | Picornavirus | Hepadnavirus | Flavivirus | Unclassified (viroid-like) | Hepevirus |
| Genome | RNA | DNA | RNA | Circular RNA | RNA |
| Envelope | Naked | Enveloped | Enveloped | Enveloped (borrows HBsAg) | Naked |
| Spread | Fecal-oral | Blood, sexual | Blood, sexual | Blood, sexual | Fecal-oral |
| Course |
|
|
|
|
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| Mortality | Under 0.5% | 1–2% | 0.5–1% | High to very high | 1–2%; about 25% in third trimester |
| Diagnosis | Anti-HAV IgM | HBsAg, anti-HBc IgM | Anti-HCV antibody (ELISA) | Anti-HDV plus HBsAg | Anti-HEV antibody (ELISA) |
| Treatment | Supportive | Interferon-alpha plus nucleoside/nucleotide RT inhibitors | Direct-acting agents: elbasvir/grazoprevir, ledipasvir/sofosbuvir | None specific | Mostly supportive; ribavirin and peginterferon for chronic cases |
- Hepatitis can also complicate CMV, EBV, congenital rubella and yellow fever
HBV virion and life cycle
- Infectious particle is the Dane particle (about 42 nm)
- Layers from outside in: surface antigen, core antigens (HBc, HBe), partly double-stranded DNA with DNA polymerase
Entry→Core to nucleus→Genome completed to cccDNA→Transcription to RNA→Reverse transcription in core→Virion budding
HBV markers
| Marker | Meaning |
|---|---|
| HBsAg | Surface antigen; present in acute disease; persistence means carrier state |
| Anti-HBs | Protective antibody; seen after recovery or vaccination |
| HBcAg | Core antigen; not detected in serum |
| Anti-HBc IgM | Recent infection; may be the only marker in the window |
| HBeAg | Marks active replication and high infectivity |
| Anti-HBe | Lower infectivity |
| Window period | HBsAg gone, anti-HBs not yet detectable |
Serologic patterns
| State | HBsAg / HBeAg / DNA | Anti-HBc IgM | Anti-HBc IgG | Anti-HBe | Anti-HBs |
|---|---|---|---|---|---|
| Acute | + | + | − | − | − |
| Window | − | + or − | + | + | − |
| Past infection | − | − | + | + | + |
| Vaccinated | − | − | − | − | + |
| Chronic | + | − | + | + or − | − |
Exam trap
- Vaccination produces anti-HBs only, with no anti-core antibody.
- Isolated anti-HBc IgM can reveal infection during the window.
🧪 DNA Viruses: Overview
General rules
- Genome is double-stranded, except parvovirus (single-stranded)
- Capsid is icosahedral, except poxvirus (complex)
- Replication in the nucleus, except poxvirus (cytoplasm)
| Family | Genome | Envelope | Replication site | Packaged polymerase | Examples |
|---|---|---|---|---|---|
| Parvo | Linear ssDNA | Naked | Nucleus | No | B19 |
| Papilloma / Polyoma | Circular dsDNA | Naked | Nucleus | No | HPV; BK, JC |
| Adeno | Linear dsDNA | Naked | Nucleus | No | Adenovirus |
| Hepadna | Circular, partly dsDNA | Enveloped | Nucleus, RNA intermediate | Yes (reverse-transcribing) | HBV |
| Herpes | Linear dsDNA | Enveloped (from nuclear membrane) | Nucleus | No | HSV, VZV, EBV, CMV, HHV-6/8 |
| Pox | Linear dsDNA | Enveloped | Cytoplasm | Yes (DNA-dependent RNA polymerase) | Variola, vaccinia, molluscum |
Concept
- Poxviruses carry their own transcription enzymes, so they can replicate in the cytoplasm.
Herpesvirus life cycle
Fusion entry→Immediate-early proteins (latency control)→Early: replication proteins and genome copying→Late: structural proteins→Nuclear assembly→Exocytosis; syncytia
🔬 Parvo, Papilloma, Polyoma, Adeno
Parvovirus B19
- Spread: respiratory, fomites, vertical
- Targets dividing erythroid precursors, causing lysis
- Anemia matters most in sickle-cell disease
- Can precipitate aplastic crisis
- Fifth disease (erythema infectiosum)
- Incubation 7–10 days
- Flu-like prodrome, then slapped-cheek rash
- Adult arthralgia from immune complexes
- Other: myocarditis
- Fetal infection
- Severe anemia, heart failure
- Hydrops fetalis, miscarriage
- Diagnosis: serology, molecular testing
- Treatment: supportive
Polyomaviruses
| Virus | Site | Disease |
|---|---|---|
| BK | Latent in kidney | Renal disease in immunosuppressed |
| JC | Oligodendrocytes | Progressive multifocal leukoencephalopathy (demyelination) in AIDS and transplant patients |
- Diagnosis: ELISA, PCR
- Treatment: supportive
Human papillomavirus
- Over 100 types, each with its own disease pattern
- Spread: direct contact, fomites
- Infects basal epithelium, causing hyperkeratosis (wart)
- Oncogenesis
- E6 inhibits p53
- E7 inhibits Rb
- Lesions by type
- Types 2, 4: common hand warts
- Type 1: deeper, painful plantar warts
- Types 6, 11: genital warts, laryngeal papillomas (benign)
- Types 16, 18: high-risk, cervical neoplasia and other anogenital and laryngeal cancers
- Also high-risk: 31, 33, 35, 45, 52, 58
- Diagnosis
- Skin: clinical
- Cervix: koilocytes on Pap smear
- PCR or in situ probes for typing
- Treatment
- Cryotherapy, laser, excision
- Podophyllin, trichloroacetic acid, 5-fluorouracil
- Imiquimod, interferon-alpha, cidofovir
- Recurrence 30–70% within 6 months
- Prevention: safe sex and recombinant capsid vaccines (4-, 9- and 2-type versions)
Adenovirus
- Naked linear dsDNA with hexon, penton and fiber proteins
- Over 50 types in subgroups A–F
- Spread: respiratory, fecal-oral, contact
- Lytic in permissive cells; transforming in nonpermissive cells
- Syndromes
- Acute respiratory disease, pneumonia (military recruits, types 4 and 7)
- Pharyngoconjunctivitis, nonpurulent (pools)
- Hemorrhagic cystitis in boys
- Gastroenteritis in daycare (types 40, 41)
- Myocarditis; severe disease in transplant recipients
- Diagnosis: serology, ELISA
- Treatment: supportive; cidofovir for severe or immunocompromised cases
- Prevention: live non-attenuated vaccine for military use
🔥 Herpesviruses and Poxviruses
Herpesvirus features
- Large enveloped dsDNA virus
- Intranuclear inclusions
- Lifelong latency
Primary versus latent sites
| Virus | Primary site | Primary illness | Latency | Reactivation |
|---|---|---|---|---|
| HSV-1 | Mucosa | Gingivostomatitis, keratoconjunctivitis | Trigeminal ganglion | Cold sores |
| HSV-2 | Mucosa | Genital and neonatal herpes | Sacral ganglia | Genital lesions |
| VZV | Respiratory mucosa | Chickenpox | Dorsal root ganglia | Zoster |
| EBV | Epithelium, B cells | Mononucleosis (heterophile positive) | B cells | Silent shedding |
| CMV | Mononuclear and epithelial cells | Heterophile-negative mononucleosis, congenital disease | Mononuclear cells | Silent shedding |
| HHV-6 | Mononuclear cells | Roseola | Mononuclear cells | Silent shedding |
| HHV-8 | Dermis | Fever, rash | B cells, glandular epithelium | Kaposi sarcoma |
HSV-1 and HSV-2
- Spread by close contact
- Vesicles, then ascent to ganglia, then stress-triggered recurrence
- HSV-1 syndromes
- Oral lesions
- Keratoconjunctivitis with dendritic ulcers
- Encephalitis: temporal lobe focus, most common sporadic viral encephalitis in the U.S.
- HSV-2 syndromes
- Painful genital vesicles
- Neonatal herpes from birth canal exposure: disseminated, encephalitic, high mortality
- Diagnosis
- Encephalitis: CSF PCR, red cells in CSF
- Skin: Tzanck smear (giant multinucleated cells, Cowdry A bodies) or immunofluorescence
- Treatment: acyclovir
- Needs viral thymidine kinase to be activated
- Resistance from thymidine kinase mutation
- Alternatives: foscarnet; famciclovir, valacyclovir, penciclovir are also acyclovir-class
Varicella-zoster virus
Respiratory entry→Nodes→Viremia→Spleen, liver→Second viremia→Skin→Dorsal root latency
- Chickenpox: fever, malaise, rash in mixed stages (asynchronous)
- Zoster: painful vesicles in one dermatome, usually older adults
- Treatment: acyclovir (oral healthy, IV immunocompromised)
- Avoid aspirin in children (Reye syndrome)
- Prevention
- Live attenuated varicella vaccine
- Recombinant zoster vaccine for older adults
- Immune globulin after exposure in the immunocompromised
Epstein-Barr virus
- Spread by saliva; most adults seropositive
- Infects pharyngeal epithelium, then B cells via CD21
- Reactive T cells appear as atypical lymphocytes (up to 70% of white cells)
- Mononucleosis: fatigue, fever, sore throat, nodes, splenomegaly
- Complications
- Lymphoproliferative disease in immunosuppression
- Oral hairy leukoplakia in AIDS
- Cancers
- Burkitt lymphoma: c-myc translocation, malaria link
- Nasopharyngeal carcinoma
- Hodgkin and some non-Hodgkin lymphomas
- Diagnosis: heterophile antibody (IgM against sheep and bovine red cells)
- Treatment: supportive
CMV
- Spread: saliva, sex, blood, transplacental
- Latent in mononuclear cells
- Most frequent congenital infection in the U.S.
- Jaundice, hepatosplenomegaly, purpura, pneumonitis, CNS damage
- Immunocompetent: heterophile-negative mononucleosis
- Immunocompromised: retinitis, colitis, pneumonitis
- Diagnosis
- Owl-eye basophilic intranuclear inclusions
- Serology, PCR, culture
- Treatment: ganciclovir or foscarnet
- Ganciclovir resistance involves the UL97 gene
- Prevention: screen blood and donor organs
HHV-6 and HHV-8
- HHV-6/7: roseola, with several days of fever then a lacy trunk rash; supportive care
- HHV-8: induces VEGF; Kaposi sarcoma in AIDS; no specific therapy
Poxviruses
- Large enveloped dsDNA, cytoplasmic replication
- Members: variola, vaccinia, molluscum, orf, monkeypox
| Virus | Key points |
|---|---|
| Variola (smallpox) |
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| Molluscum contagiosum |
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| Monkeypox |
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RNA virus ground rules
- All single-stranded, except reovirus (double-stranded)
- (−)RNA viruses carry RNA-dependent RNA polymerase
- Reovirus, arenavirus and retrovirus also carry virion enzymes
- Naked RNA viruses: picorna, calici, hepe, reo; the rest are enveloped
- Segmented genomes: reovirus, orthomyxovirus, bunyavirus, arenavirus
High-yield
- Segmented genomes allow reassortment, which drives influenza antigenic shift.