Microbiology chapters
Virus structure and host defence
What viruses are made of (nucleic acid, capsid, envelope), how they replicate, how DNA and RNA viruses are classified, the outcomes of infection (lytic, persistent, latent, transforming), and how the body fights them: interferons, complement, natural killer cells, cytotoxic T cells and antibodies, plus laboratory diagnosis of viral infection.
In 30 seconds
- A virion is nucleic acid (DNA or RNA, never both) inside a protein capsid (icosahedral or helical), sometimes surrounded by a lipid envelope with glycoprotein spikes taken from host membranes; enveloped viruses are fragile (killed by detergents, ether, drying) and spread by blood, sex and droplets, while naked viruses (polio, hepatitis A, rotavirus, norovirus, adenovirus) are tough and spread faecal-orally.
- Rules of thumb: DNA viruses are double-stranded (except parvovirus B19), mostly replicate in the nucleus (except poxviruses); RNA viruses are single-stranded (except reovirus/rotavirus), mostly replicate in the cytoplasm (except influenza and retroviruses); negative-sense RNA viruses carry their own RNA-dependent RNA polymerase; segmented genomes (influenza) allow reassortment (antigenic shift); herpesviruses become latent and reactivate.
- Host defence: interferons α and β (from infected cells) put neighbouring cells into an antiviral state (degrade mRNA, block translation), interferon-γ activates macrophages and NK cells; NK cells kill infected cells that lose MHC class I; CD8 cytotoxic T cells clear infection; neutralising antibodies (IgG, secretory IgA) block entry and prevent reinfection; complement lyses enveloped viruses and infected cells.
On this page
What is a virus?
- Obligate intracellular parasites: no metabolism or ribosomes of their own; replicate only inside living cells.
- Contain either DNA or RNA, never both.
- Very small (about 20–300 nm): seen only by electron microscopy (poxviruses are the largest; parvoviruses among the smallest).
- Not affected by antibiotics.
- Prions (misfolded proteins, no nucleic acid) and viroids are related "unconventional" agents.
Structure
| Component | Details |
|---|---|
| Genome | DNA or RNA; single or double-stranded; linear, circular or segmented |
| Capsid | Protein coat made of capsomeres; protects the genome; nucleocapsid = genome + capsid |
| Symmetry | Icosahedral (cubic: 20 faces; most DNA viruses, picornaviruses) or helical (most negative-sense RNA viruses: influenza, measles, rabies); complex (poxviruses) |
| Envelope | Lipid bilayer from the host cell membrane (nuclear membrane in herpesviruses) with viral glycoprotein spikes (attachment, fusion; e.g. haemagglutinin and neuraminidase in influenza) |
| Enzymes | Some carry polymerases (negative-sense RNA viruses), reverse transcriptase (retroviruses, hepatitis B) |
| Feature | Enveloped viruses | Naked (non-enveloped) viruses |
|---|---|---|
| Stability | Fragile: killed by detergents, ether, alcohol, drying, acid, bile | Hardy: resist drying, acid, bile, detergents |
| Spread | Respiratory droplets, blood, sex, organ transplants | Faecal-oral, fomites |
| Release | Budding (cell may survive) | Lysis of the cell |
| Examples | Herpesviruses, HIV, hepatitis B and C, influenza, measles, mumps, rubella, rabies, dengue, SARS-CoV-2, poxviruses | Polio and other enteroviruses, hepatitis A and E, rotavirus, norovirus, adenovirus, HPV, parvovirus B19 |
Classification (key families)
DNA viruses
All are double-stranded except Parvoviridae (single-stranded). All are icosahedral except poxviruses (complex). All replicate in the nucleus except poxviruses (cytoplasm, carry their own polymerase).
| Family | Envelope | Examples |
|---|---|---|
| Herpesviridae | Yes | HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-8 |
| Hepadnaviridae | Yes | Hepatitis B (partly double-stranded; reverse transcriptase) |
| Poxviridae | Yes (complex) | Smallpox, molluscum contagiosum, mpox |
| Adenoviridae | No | Adenovirus (pharyngitis, conjunctivitis, gastroenteritis, haemorrhagic cystitis) |
| Papillomaviridae | No | HPV (warts, cervical cancer) |
| Polyomaviridae | No | JC virus (progressive multifocal leukoencephalopathy), BK virus |
| Parvoviridae | No | Parvovirus B19 (single-stranded DNA): erythema infectiosum ("slapped cheek"), aplastic crisis in sickle cell, hydrops fetalis |
RNA viruses
All are single-stranded except Reoviridae (rotavirus: double-stranded). Most replicate in the cytoplasm except influenza and retroviruses (nucleus).
- Positive-sense (+) RNA: acts directly as mRNA; naked RNA is infectious: picornaviruses (polio, coxsackie, hepatitis A, rhinovirus), flaviviruses (dengue, hepatitis C, yellow fever, Zika, West Nile), togaviruses (rubella, chikungunya), coronaviruses (SARS-CoV-2), caliciviruses (norovirus), hepeviruses (hepatitis E), retroviruses (HIV: + RNA copied to DNA by reverse transcriptase).
- Negative-sense (−) RNA: must be copied to + RNA first, so the virion carries RNA-dependent RNA polymerase: orthomyxoviruses (influenza: segmented), paramyxoviruses (measles, mumps, RSV, parainfluenza), rhabdoviruses (rabies), filoviruses (Ebola), bunyaviruses (Crimean-Congo haemorrhagic fever), arenaviruses (Lassa).
- Segmented genomes: influenza, rotavirus, bunyaviruses, arenaviruses → reassortment (new strains: influenza antigenic shift).
Replication cycle
- Attachment: viral proteins bind specific host receptors (decides tropism): HIV gp120 → CD4 (+ CCR5/CXCR4); influenza haemagglutinin → sialic acid; SARS-CoV-2 spike → ACE2; rabies → acetylcholine receptor; EBV → CD21 (CR2) on B cells.
- Penetration: endocytosis or membrane fusion.
- Uncoating: release of the genome. The eclipse period follows: no infectious virus can be found in the cell.
- Synthesis: early proteins (enzymes), genome replication, late proteins (structural).
- Assembly of new virions.
- Release: lysis (naked viruses) or budding (enveloped viruses).
One infected cell can release thousands of new virions.
Outcomes of infection in the cell
| Type | Features | Examples |
|---|---|---|
| Lytic (cytocidal) | Cell killed; cytopathic effect in culture | Polio, influenza |
| Persistent (chronic) | Virus produced continuously | Hepatitis B, C, HIV |
| Latent | Genome stays dormant (no virus produced), reactivates later | Herpesviruses: HSV (sensory ganglia: cold sores), VZV (dorsal root ganglia: shingles), EBV (B cells), CMV (monocytes) |
| Transforming (oncogenic) | Cell becomes malignant | HPV (cervix), EBV (Burkitt, nasopharyngeal carcinoma), HBV, HCV (liver), HTLV-1 (T-cell leukaemia), HHV-8 (Kaposi sarcoma), Merkel cell polyomavirus |
| Slow virus infections | Long incubation, progressive | Subacute sclerosing panencephalitis (measles), PML (JC virus), prion diseases |
Inclusion bodies (seen on histology):
- Negri bodies: rabies (cytoplasmic, in neurons of the hippocampus and Purkinje cells).
- Owl's eye intranuclear inclusions: CMV.
- Cowdry type A intranuclear: herpes simplex, VZV.
- Guarnieri bodies: poxviruses (cytoplasmic).
- Molluscum bodies: molluscum contagiosum.
- Warthin-Finkeldey giant cells: measles.
- Koilocytes: HPV.
Host defence against viruses
Innate defences
- Interferons:
- IFN-α (leucocytes) and IFN-β (fibroblasts and other infected cells): made by infected cells; act on neighbouring cells to create an antiviral state (induce enzymes that degrade viral mRNA (RNase L) and block protein synthesis (protein kinase R phosphorylates eIF2)); not virus-specific but species-specific. Also increase MHC I expression and activate NK cells. Therapeutic: IFN-α (formerly hepatitis B and C), IFN-β (multiple sclerosis).
- IFN-γ (T cells, NK cells): activates macrophages, increases MHC expression; immune regulation.
- Natural killer (NK) cells: kill virus-infected and tumour cells that reduce MHC class I expression ("missing self"); act early (days), before T cells; also antibody-dependent cell-mediated cytotoxicity (via Fc receptors, CD16).
- Complement: lyses enveloped viruses and infected cells; opsonises; activated by antibody (classical) and directly (alternative, lectin pathways).
- Fever, macrophages, physical barriers (skin, mucus, cilia), acidity.
Adaptive defences
- Cytotoxic CD8 T cells: recognise viral peptides on MHC class I and kill infected cells (perforin, granzymes): the main mechanism for clearing established infections. Also cause much of the tissue damage (hepatitis B liver damage).
- Helper CD4 T cells: help B cells and CD8 cells.
- Antibodies:
- Neutralising antibodies block attachment and entry; most important in preventing reinfection and in vaccine protection.
- Secretory IgA protects mucosal surfaces (oral polio vaccine induces gut IgA).
- IgM shows recent infection (diagnosis); IgG shows past infection or immunity.
- Opsonisation, complement activation, ADCC.
How viruses evade defences
- Antigenic variation: drift (point mutations) and shift (reassortment) in influenza; rapid mutation in HIV, hepatitis C.
- Latency (herpesviruses).
- Reducing MHC class I (CMV, adenovirus) to escape CD8 cells.
- Infecting immune cells (HIV destroys CD4 cells; measles causes immunosuppression; EBV infects B cells).
- Blocking interferon (hepatitis C, influenza NS1).
- Spreading cell to cell without exposure to antibody.
Laboratory diagnosis of viral infections
| Method | Examples |
|---|---|
| Nucleic acid detection (PCR, RT-PCR) | The main method today: SARS-CoV-2, HIV and hepatitis viral loads, HSV in CSF, influenza, dengue (early) |
| Antigen detection | Rapid tests: HBsAg, dengue NS1, influenza, rotavirus, SARS-CoV-2 antigen |
| Serology | IgM (acute infection), rising IgG (fourfold rise in paired sera), IgG avidity |
| Culture in cell lines | Cytopathic effect, haemadsorption; slow, now less used |
| Microscopy | Electron microscopy (rotavirus), inclusion bodies on histology, Tzanck smear (multinucleated giant cells: HSV, VZV) |
Prevention and treatment
- Vaccines: live attenuated (measles, mumps, rubella, oral polio, rotavirus, varicella, yellow fever) and inactivated/subunit (injectable polio, hepatitis A and B, HPV, influenza, rabies, COVID-19 mRNA and vector vaccines).
- Passive immunisation: immunoglobulins (rabies, hepatitis B, VZV, tetanus).
- Antivirals target viral steps: entry (maraviroc), uncoating (amantadine), polymerase (aciclovir, sofosbuvir), reverse transcriptase (tenofovir), protease (lopinavir), integrase (dolutegravir), release (oseltamivir).
Exam focus
Expect: viral components and envelope properties, naked vs enveloped spread and resistance, DNA virus exceptions (parvovirus single-stranded, poxvirus cytoplasmic), RNA virus exceptions (rotavirus double-stranded, influenza and retroviruses nuclear), positive vs negative sense, segmented genomes and reassortment, replication steps and receptors (CD4, ACE2, sialic acid, CD21), latency in herpesviruses, oncogenic viruses, inclusion bodies (Negri, owl's eye), interferon actions, NK cells and MHC I, CD8 T cells, neutralising antibodies and IgA, IgM vs IgG in diagnosis.
Quick revision
- DNA or RNA, never both; capsid ± envelope.
- Enveloped: fragile, blood/sex/droplets. Naked: hardy, faecal-oral.
- DNA viruses: ds (except parvovirus B19), nuclear (except poxvirus).
- RNA viruses: ss (except rotavirus), cytoplasmic (except influenza, retroviruses).
- Negative-sense RNA carries RNA-dependent RNA polymerase; segmented → reassortment.
- Herpesviruses: latent; reactivate.
- Interferon α/β: antiviral state; IFN-γ: activates macrophages; NK cells kill MHC I-low cells; CD8 T cells clear infection; neutralising antibodies prevent reinfection.
- Negri bodies: rabies. Owl's eye: CMV.
Written by The House Job from standard microbiology references (Levinson's Review of Medical Microbiology and Immunology).
FAQ
Which DNA virus is single-stranded?
Parvovirus B19.
Why are enveloped viruses easily killed by detergents?
Their envelope is a lipid membrane taken from the host cell, which detergents, alcohol and drying destroy; without it the virus cannot attach and enter cells.
How do interferons protect cells?
Interferons alpha and beta, released by infected cells, act on neighbouring cells to switch on enzymes that break down viral RNA and block protein synthesis, creating an antiviral state.
Which inclusion bodies are seen in rabies?
Negri bodies, in the cytoplasm of neurons.