For education and revision only. Not individual medical advice; check current NICE/BNF and local guidance before clinical use. Clinical safety and terms.
Microbiology: Virology - structure, replication and important viral infections
🦠 Virology - structure, replication and important viral infections. Viruses cause most respiratory and many gastrointestinal infections, blood-borne infections that need lifelong management, congenital infections, and several cancers. Antibiotics do not work against them; prevention relies on vaccination and infection control, and treatment on specific antivirals that target viral replication steps. This chapter covers viral structure and replication, then the clinically important virus families, and how they are diagnosed and treated. Your four questions for a suspected viral infection: Which organ system and which host (immunocompromised, pregnant, neonate)? Is it acute, latent or chronic? Which test - PCR (acute), IgM/IgG serology (immunity or recent infection) or antigen? Is there an antiviral, an exposure prophylaxis or a public health action?
Viral Structure and Classification
Viruses - obligate intracellular parasites (20–300 nm); a genome (DNA or RNA) inside a protein capsid, with or without a lipid envelope derived from host membranes.
Enveloped viruses (herpes, influenza, HIV, hepatitis B and C, coronaviruses, measles) are destroyed by alcohol, detergents and drying; non-enveloped viruses (norovirus, adenovirus, enteroviruses, hepatitis A and E, HPV, rotavirus) resist alcohol gel and survive on surfaces - use soap and water and chlorine-based cleaning.
Latency - genome persists without active replication, reactivating with immunosuppression or stress: herpesviruses (HSV in sensory ganglia - cold sores; VZV in dorsal root ganglia - shingles; CMV and EBV in leucocytes), HIV (integrated provirus - reservoir prevents cure).
Aciclovir within 72 h for shingles (and adults with chickenpox); VZIG/aciclovir post-exposure prophylaxis for susceptible pregnant women and the immunosuppressed; Shingrix vaccine
Other DNA Viruses - Adenovirus, HPV, Parvovirus, Pox
Adenovirus - conjunctivitis (outbreaks - highly contagious, non-enveloped), pharyngoconjunctival fever, gastroenteritis in children, haemorrhagic cystitis and disseminated disease after stem cell transplant (cidofovir).
HPV - low-risk types 6 and 11 cause anogenital warts and recurrent respiratory papillomatosis; high-risk types cause cancers. UK school vaccination (9-valent Gardasil 9, single dose from 2023) for boys and girls aged 12–13; cervical screening by primary HPV testing.
Parvovirus B19 - infects red cell precursors: slapped cheek syndrome (erythema infectiosum - fifth disease) in children; symmetrical arthropathy in adults; aplastic crisis in haemolytic anaemias (sickle cell, spherocytosis); chronic anaemia in the immunocompromised; hydrops fetalis in pregnancy (especially before 20 weeks - refer to fetal medicine for monitoring and intrauterine transfusion).
Polyomaviruses - JC virus → progressive multifocal leukoencephalopathy (HIV, natalizumab, rituximab); BK virus → nephropathy in renal transplants, haemorrhagic cystitis after stem cell transplant.
Poxviruses - molluscum contagiosum (pearly umbilicated papules - children; extensive in HIV); mpox (clade II outbreak 2022 mainly among MSM - genital/perianal lesions, proctitis, lymphadenopathy; clade I outbreaks in central Africa since 2023 - UKHSA guidance; MVA-BN vaccine); smallpox eradicated (1980).
Influenza A and B - seasonal epidemics (winter); antigenic drift (point mutations - annual vaccine update) and antigenic shift (reassortment of segments between human and animal strains - pandemics, e.g. 1918, 2009 H1N1; avian H5N1 a current concern). Sudden fever, myalgia, cough; complications - primary viral pneumonia, secondary bacterial pneumonia (S. aureus, pneumococcus), myocarditis. Antivirals (NICE TA168): oseltamivir within 48 hours for at-risk groups when influenza is circulating; annual vaccination for over-65s, at-risk groups, pregnant women, healthcare workers and children (live attenuated nasal vaccine).
RSV - bronchiolitis in infants (peak November–December), pneumonia in older adults; UK RSV vaccination programme from September 2024 for pregnant women from 28 weeks (protects infants) and older adults from age 75 (check current UKHSA eligibility - the age range is being extended); nirsevimab/palivizumab for high-risk infants.
SARS-CoV-2 (COVID-19) - ACE2 receptor; spectrum from asymptomatic to ARDS, thrombosis, myocarditis, long COVID; antivirals for high-risk outpatients (nirmatrelvir–ritonavir, molnupiravir, sotrovimab per NICE), dexamethasone for patients needing oxygen, IL-6 inhibitors in severe disease; seasonal boosters for older and vulnerable groups.
Rhinovirus (commonest cause of the common cold; asthma and COPD exacerbations), parainfluenza (croup), human metapneumovirus (bronchiolitis-like), seasonal coronaviruses.
Norovirus - commonest cause of gastroenteritis in all ages in the UK; winter vomiting; very low infective dose; outbreaks in hospitals, care homes and cruise ships; ward closures; soap and water (alcohol gel ineffective); isolate until 48 hours symptom-free.
Rotavirus - severe gastroenteritis in infants; oral live vaccine at 8 and 12 weeks (contraindicated in severe combined immunodeficiency; small risk of intussusception).
Enteroviruses (coxsackie, echovirus, enterovirus 71, poliovirus) - viral meningitis (commonest cause), hand, foot and mouth disease, herpangina, myocarditis and pericarditis (coxsackie B), Bornholm disease (pleurodynia), acute flaccid myelitis (EV-D68). Polio - eradication nearly complete (wild polio remains in Pakistan and Afghanistan; vaccine-derived poliovirus detected in London sewage in 2022 → booster campaign).
Hepatitis A and E - faeco-oral (see Hepatitis Viruses).
Measles - extremely contagious (R0 12–18); prodrome of fever, cough, coryza, conjunctivitis, Koplik spots, then maculopapular rash spreading from the face downwards; complications - pneumonia, otitis media, encephalitis, subacute sclerosing panencephalitis (years later), severe disease in malnutrition and immunosuppression. Outbreaks in England with falling MMR uptake (2023–2024). Notify on suspicion; exclude for 4 days after the rash; post-exposure MMR (within 72 hours) or human normal immunoglobulin (within 6 days) for susceptible contacts.
Rubella - mild illness with rash and post-auricular/occipital lymphadenopathy, arthralgia; congenital rubella syndrome (first 16 weeks - cataracts, sensorineural deafness, congenital heart disease - PDA, pulmonary stenosis); now rare in the UK (MMR). Non-immune women are offered MMR after delivery (live vaccine - not in pregnancy).
Arboviruses (in returning travellers):dengue (Aedes mosquito - fever, severe myalgia and retro-orbital pain, rash, thrombocytopenia, leucopenia; severe dengue with plasma leakage on second infection with a different serotype; avoid NSAIDs), Zika (microcephaly when acquired in pregnancy; sexual transmission), chikungunya (severe prolonged arthralgia), yellow fever (jaundice, haemorrhage; vaccine required for some countries), Japanese encephalitis, West Nile virus, tick-borne encephalitis (Europe; cases acquired in England reported since 2019).
Rabies - bites or scratches from bats or mammals abroad (and UK bats - European bat lyssavirus); almost 100% fatal once symptomatic; post-exposure prophylaxis (wound washing, vaccine ± rabies immunoglobulin) via UKHSA.
Viral haemorrhagic fevers (Ebola, Marburg, Lassa, Crimean–Congo) - returning travellers within 21 days with fever from endemic areas → VHF risk assessment, isolation, urgent discussion with infectious diseases and UKHSA.
Acute hepatitis, more severe in adults; IgM anti-HAV; vaccine for travellers, MSM, chronic liver disease
Hepatitis B (DNA)
Blood, sexual, vertical
90% if infected at birth; about 5% in adults
HBsAg (infection), anti-HBc IgM (acute), HBeAg (high infectivity), HBV DNA (load), anti-HBs (immunity - vaccine gives anti-HBs only); tenofovir or entecavir; vaccine plus HBIG at birth for babies of infected mothers; routine infant vaccination (6-in-1)
Hepatitis C (RNA)
Blood - injecting drug use (main UK route), historical transfusion, tattoos abroad, sexual (MSM)
About 75% become chronic
Antibody screen then HCV RNA; direct-acting antivirals cure >95% in 8–12 weeks (e.g. sofosbuvir–velpatasvir, glecaprevir–pibrentasvir); no vaccine; NHS England elimination target
Hepatitis D (RNA)
Requires hepatitis B (co-infection or superinfection)
Worsens HBV disease
Prevented by HBV vaccination; bulevirtide
Hepatitis E (RNA)
Genotype 3 - undercooked pork, game, shellfish in the UK (zoonotic); genotype 1 - water-borne in South Asia
Chronic only in the immunosuppressed (transplant)
Commonest acute viral hepatitis in the UK; severe in pregnancy (genotype 1); Guillain–Barré, neuralgic amyotrophy; screened in blood donations
Hepatitis B serology interpretation:
Pattern
HBsAg
Anti-HBc
Anti-HBs
Never infected, not vaccinated
−
−
−
Vaccinated
−
−
+
Past infection (cleared)
−
+
+ (usually)
Chronic infection
+
+ (IgG)
−
Acute infection
+
+ (IgM)
−
Hepatitis B reactivation - screen (HBsAg and anti-HBc) before rituximab, chemotherapy, high-dose steroids and other immunosuppression; prophylactic antivirals if positive.
Retrovirus infecting CD4 T cells (via CD4 and the CCR5 or CXCR4 co-receptor); reverse transcription and integration into host DNA. HIV-1 (worldwide), HIV-2 (West Africa - less pathogenic).
Transmission - sexual (anal sex highest risk), blood (injecting, needlestick - about 0.3% per percutaneous exposure), vertical (pregnancy, delivery, breastfeeding).
Primary HIV infection (seroconversion) - 2–6 weeks after exposure in most: fever, maculopapular rash, sore throat, lymphadenopathy, mouth ulcers, aseptic meningitis; highly infectious. Fourth-generation tests (p24 antigen + antibody) detect most infections by 4 weeks (window period up to 45 days).
HIV indicator conditions - offer an HIV test to anyone with TB, lymphoma, cervical/anal cancer, STI, hepatitis B or C, unexplained weight loss or fever, pneumonia of unusual severity, shingles in more than one dermatome, seborrhoeic dermatitis, unexplained thrombocytopenia, oral candida, mononucleosis-like illness (BHIVA). Opt-out testing in emergency departments in high-prevalence areas of England.
Antiretroviral therapy (ART) - start at diagnosis regardless of CD4 count (usually two NRTIs plus an integrase inhibitor, e.g. bictegravir/emtricitabine/tenofovir alafenamide; long-acting injectable cabotegravir + rilpivirine every 2 months for suppressed patients). Check HLA-B*57:01 before abacavir.
U=U (Undetectable = Untransmittable) - an undetectable viral load on ART for 6 months means no sexual transmission.
Prevention:PrEP (tenofovir/emtricitabine - free on the NHS), PEP (within 72 hours, ideally within 24, for 28 days), condoms, treatment as prevention, antenatal screening and ART (vertical transmission <0.3%).
Immune reconstitution inflammatory syndrome (IRIS) - paradoxical worsening of an opportunistic infection (TB, cryptococcus) after starting ART.
Scenario. A pregnant woman at 20 weeks has been in contact with a child with chickenpox. She is unsure if she has had it. What do you do?
Answer: Check VZV IgG urgently (stored booking blood if available). If non-immune, give post-exposure prophylaxis - oral aciclovir from day 7 to 14 after exposure (RCOG/UKHSA), or VZIG in selected cases. If she develops chickenpox, give oral aciclovir within 24 hours of the rash and advise urgent review if respiratory or neurological symptoms develop.
Scenario. HBsAg negative, anti-HBc positive, anti-HBs positive. What does this mean, and does it matter before rituximab?
Answer: Past (resolved) hepatitis B infection. Before rituximab there is a risk of reactivation - discuss with hepatology; prophylactic antiviral therapy (e.g. entecavir or tenofovir) or close HBV DNA monitoring.
Scenario. A nurse has a needlestick injury from a patient with known HIV with an undetectable viral load.
Answer: Wash the wound, encourage bleeding, report to occupational health. PEP is generally not recommended when the source has a sustained undetectable viral load on ART (BHIVA), but this should be discussed urgently with the occupational health or infectious diseases team; baseline bloods; follow-up testing.