Virology
1. What this chapter covers, and how NEET PG actually tests it
Virology is examined less as a catalogue of organisms and more as a set of consequences. Stems give a serology panel, a CD4 count, an exposure history or a vaccine question and expect the reasoning that follows.
The organising principle is that the genome and the envelope predict the behaviour.
Genome type sets the replication site, the mutation rate and therefore whether a durable vaccine is achievable. The envelope sets survival outside the host and therefore the route of transmission and the disinfection required.
| Property | What it predicts |
|---|---|
| DNA genome | Nuclear replication, proofreading, low mutation rate, stable vaccines |
| RNA genome | Cytoplasmic replication, no proofreading, high mutation rate |
| Segmented RNA | Reassortment, sudden antigenic shift, pandemic potential |
| Enveloped | Fragile outside host, needs close contact or fluid, killed by soap and alcohol |
| Naked | Survives on surfaces and in the gut, faecal-oral or fomite spread, resists detergents |
Two exceptions must be held alongside the rule. Poxviruses are DNA viruses that replicate in the cytoplasm because they carry their own polymerase, and retroviruses and hepatitis B both use reverse transcriptase, which is why both mutate readily and why one drug class treats them both.
2. Fundamentals
2.1 Structure
A virus is a genome in a protein capsid, sometimes wrapped in a host-derived lipid envelope studded with viral glycoproteins.
The capsid is either icosahedral or helical, and this is fixed for a family.
The envelope is stolen host membrane, usually plasma membrane, but herpesviruses take theirs from the nuclear membrane, which is consistent with their nuclear assembly.
Because the envelope is lipid, alcohol, soap and lipid solvents destroy enveloped viruses easily. Naked viruses need oxidising agents such as hypochlorite.
This single fact explains why hand rub works for influenza, SARS-CoV-2 and HIV, but chlorination is needed for hepatitis A, polio and rotavirus.
2.2 The replication cycle and where drugs act
Every virus follows the same six steps, and every antiviral drug class blocks one of them.
| Step | Example drug target |
|---|---|
| Attachment and entry | Maraviroc (CCR5), enfuvirtide (gp41) |
| Uncoating | Amantadine (influenza A M2 channel) |
| Genome replication | Acyclovir, tenofovir, remdesivir, sofosbuvir |
| Integration | Dolutegravir, raltegravir |
| Assembly and maturation | Protease inhibitors |
| Release | Oseltamivir, zanamivir (neuraminidase) |
Most antivirals are nucleoside analogues that target polymerase, because polymerase is the one enzyme almost every virus must supply itself.
That also explains why antivirals are narrow-spectrum. There is no viral equivalent of the shared bacterial cell wall.
2.3 The eclipse phase
After entry, infectious virus disappears from the cell before progeny appear. This is the eclipse phase.
The one-step growth curve concept is occasionally examined directly, and the term to attach to the interval before extracellular virus reappears is the latent period.
3. Hepatitis viruses
3.1 Sorting the five by route
Route separates them cleanly, and route follows the envelope.
| Virus | Genome | Envelope | Route | Chronicity |
|---|---|---|---|---|
| HAV | RNA | Naked | Faecal-oral | Never |
| HBV | DNA | Enveloped | Blood, sexual, vertical | Yes |
| HCV | RNA | Enveloped | Blood | Yes, commonly |
| HDV | RNA | Needs HBsAg | Blood | Only with HBV |
| HEV | RNA | Naked | Faecal-oral, waterborne | Rarely |
The naked ones are faecal-oral and never or rarely chronic; the enveloped ones are blood-borne and can persist. This is not coincidence, since a virus that survives the gut has no need of persistence to be transmitted.
3.2 Hepatitis B serology read as a timeline
HBV serology defeats candidates only when the markers are memorised as a list rather than placed in sequence.
HBsAg appears first and defines current infection, whether acute or chronic. Persistence beyond six months means chronic infection.
Anti-HBs appears last and means immunity, from recovery or from vaccination.
IgM anti-HBc marks acute infection, and is the only marker present during the window period when HBsAg has cleared but anti-HBs has not yet appeared.
HBeAg indicates active replication and high infectivity, and its presence in a pregnant woman sharply raises vertical transmission risk.
| Pattern | Interpretation |
|---|---|
| HBsAg positive, IgM anti-HBc positive | Acute infection |
| HBsAg positive, IgG anti-HBc positive | Chronic infection |
| Anti-HBs alone positive | Vaccinated |
| Anti-HBs and anti-HBc both positive | Past resolved infection |
| IgM anti-HBc alone positive | Window period |
The distinction between vaccinated and recovered is a favourite. Vaccine contains surface antigen only, so it cannot generate anti-HBc. Any anti-HBc means the person met the whole virus.
3.3 Hepatitis D, E and the clinical traps
HDV is a defective virus that borrows HBsAg as its coat, so it can only infect an HBV carrier.
Coinfection means both acquired together and usually resolves; superinfection means HDV arriving in an established carrier and carries a high risk of fulminant hepatitis.
Hepatitis E is the one to attach to pregnancy, where mortality in the third trimester reaches roughly twenty per cent, far above the near-trivial mortality in other adults.
Hepatitis E is also the commonest cause of large waterborne epidemic jaundice in India, and can become chronic in transplant recipients on immunosuppression.
Hepatitis C is now curable with direct-acting antivirals such as sofosbuvir combined with velpatasvir or daclatasvir, with cure rates above ninety per cent, and there is still no HCV vaccine because of its extreme genotypic variability.
4. HIV
4.1 Structure and tropism
HIV is an enveloped retrovirus with two copies of positive-sense single-stranded RNA and three essential enzymes: reverse transcriptase, integrase and protease.
gp120 binds CD4 and gp41 mediates fusion. A co-receptor is also required, and which one determines cell tropism.
CCR5-tropic strains infect macrophages and dominate early infection; CXCR4-tropic strains infect T cells and emerge later, coinciding with faster decline.
A homozygous CCR5-delta32 deletion confers near-complete resistance to sexually transmitted HIV, which is the biological basis of maraviroc and of the reported cures after stem cell transplant from delta32 donors.
4.2 Natural history sorted by CD4 count
The CD4 count is the single most useful predictor in a stem, because opportunistic infections appear at reproducible thresholds.
| CD4 (cells/mm³) | Characteristic infection |
|---|---|
| Below 200 | Pneumocystis jirovecii pneumonia |
| Below 100 | Toxoplasma encephalitis, cryptococcal meningitis |
| Below 50 | CMV retinitis, disseminated Mycobacterium avium complex |
Tuberculosis is the exception that matters most in India, because it occurs at any CD4 count and is the commonest opportunistic infection and leading cause of death in Indian people living with HIV.
Cotrimoxazole prophylaxis is started below 200 and covers Pneumocystis and Toxoplasma together.
4.3 Diagnosis
Antibody tests are the mainstay, but the window period must be respected.
Fourth-generation assays detect p24 antigen along with antibody and shorten the window to around two to three weeks.
India's national testing strategy uses three rapid tests with different antigens or principles, and a diagnosis is made only when all three are reactive.
Infant diagnosis cannot use antibody, because maternal IgG crosses the placenta and persists up to eighteen months. Infants require DNA PCR, which detects proviral DNA rather than maternal antibody.
Viral load, not CD4, is used to monitor treatment response, and the target on effective therapy is suppression below the assay's detection limit.
4.4 Treatment and prophylaxis
India's preferred first-line regimen is TLD: tenofovir, lamivudine and dolutegravir, given as a single fixed-dose combination once daily, and it now anchors first-line therapy under the national programme.
Dolutegravir replaced efavirenz as the anchor because of higher potency, a much higher genetic barrier to resistance and better tolerability.
Treatment is offered to everyone at diagnosis regardless of CD4 count, since early therapy improves survival and an undetectable viral load means the person does not transmit sexually.
Post-exposure prophylaxis after needlestick uses three drugs for twenty-eight days and should begin within hours, ideally under two, and certainly within seventy-two.
Pre-exposure prophylaxis with tenofovir-based combinations is offered to people at substantial ongoing risk.
5. Respiratory viruses
5.1 Influenza: drift and shift
Influenza illustrates why a segmented genome matters.
Antigenic drift is gradual point mutation in haemagglutinin and neuraminidase, occurs in influenza A and B, and causes seasonal epidemics. It is why the vaccine is reformulated annually.
Antigenic shift is abrupt reassortment of whole genome segments between strains infecting one host, occurs only in influenza A, and causes pandemics because the population has no prior immunity.
Shift requires segmentation, and only influenza A has the animal reservoirs, particularly aquatic birds and pigs, that supply the second strain.
Haemagglutinin mediates attachment to sialic acid receptors; neuraminidase cleaves sialic acid to release progeny, which is why oseltamivir blocks release rather than entry.
Oseltamivir is most useful within forty-eight hours of symptom onset.
5.2 Coronaviruses and other respiratory agents
SARS-CoV-2 is an enveloped positive-sense RNA virus that enters via the ACE2 receptor using spike protein primed by the protease TMPRSS2.
Respiratory syncytial virus is the commonest cause of bronchiolitis in infants and forms multinucleated syncytia in culture.
Parainfluenza virus causes croup, and adenovirus, a naked DNA virus, causes pharyngoconjunctival fever and survives well on surfaces and in swimming pools.
6. Exanthematous and neurotropic viruses
6.1 Measles, rubella and varicella
Measles produces Koplik spots on the buccal mucosa before the rash, and its rare late complication is subacute sclerosing panencephalitis, appearing years afterwards.
Measles causes profound transient immune suppression, which is why post-measles pneumonia and diarrhoea, not the rash, drive its mortality.
Rubella is mild in children but teratogenic in early pregnancy, producing the triad of cataract, sensorineural deafness and patent ductus arteriosus.
India has set 2026 as its target for measles and rubella elimination, with a national campaign pursuing coverage above ninety-five per cent in every district. First-dose coverage stood near ninety-four per cent in 2024 to 2025 and second-dose coverage slightly lower.
Varicella-zoster causes chickenpox on first exposure, then becomes latent in dorsal root ganglia and reactivates as shingles in a dermatomal distribution.
6.2 Rabies
Rabies is a bullet-shaped negative-sense RNA virus that travels centripetally along peripheral nerves to the central nervous system.
Negri bodies are the eosinophilic cytoplasmic inclusions, most abundant in hippocampal and Purkinje neurons.
The incubation period varies with distance from the brain, which is why bites on the face carry the shortest interval and the greatest urgency.
Rabies is effectively one hundred per cent fatal once symptoms begin, so the entire clinical question is prophylaxis.
| Category | Exposure | Action |
|---|---|---|
| I | Touching, feeding, intact skin licked | Wash only, no vaccine |
| II | Minor scratch, nibbling without bleeding | Wash and vaccinate |
| III | Transdermal bite, mucosal contact, bat exposure | Wash, vaccinate and infiltrate immunoglobulin |
Under India's national programme the intradermal schedule is 0.1 mL at two sites on days 0, 3, 7 and 28, and the intramuscular alternative is 1 mL on days 0, 3, 7, 14 and 28.
Immunoglobulin is infiltrated into and around the wound, not given systemically, because its purpose is local neutralisation before the virus reaches nerve endings.
6.3 Polio, enteroviruses and Japanese encephalitis
Poliovirus is a naked enterovirus causing asymmetric flaccid paralysis with intact sensation, reflecting anterior horn cell destruction.
India was certified polio-free in 2014, and inactivated vaccine has been introduced alongside oral vaccine to remove the risk of vaccine-derived paralytic disease.
Japanese encephalitis is a mosquito-borne flavivirus with pigs as amplifying host and ardeid water birds as reservoir, and vaccination is part of the programme in endemic Indian districts.
6.4 Dengue and the arboviruses
Dengue is a flavivirus with four serotypes, transmitted by Aedes aegypti, and infection gives lasting immunity only to the infecting serotype.
Second infection with a different serotype is the dangerous one. Cross-reactive but non-neutralising antibody from the first infection binds the new serotype and ferries it into macrophages through Fc receptors, a mechanism called antibody-dependent enhancement.
That mechanism explains why severe dengue with plasma leakage is largely a disease of secondary infection, and why a vaccine safe in the seropositive can harm the seronegative.
NS1 antigen is detectable from day one and is the test of choice in the first five days; IgM becomes useful after that.
Chikungunya shares the same vector and produces disabling symmetrical polyarthralgia that can persist for months, which is the feature separating it from dengue at the bedside.
7. Oncogenic viruses
A small set of viruses causes a large share of infection-attributable cancer, and each acts by a definable mechanism.
| Virus | Cancer | Mechanism |
|---|---|---|
| HPV 16 and 18 | Cervical, oropharyngeal | E6 degrades p53, E7 inactivates RB |
| HBV, HCV | Hepatocellular carcinoma | Chronic inflammation and regeneration |
| EBV | Burkitt, nasopharyngeal carcinoma | LMP1 mimics constitutive CD40 signalling |
| HTLV-1 | Adult T-cell leukaemia | Tax protein transactivation |
| HHV-8 | Kaposi sarcoma | Viral cyclin and anti-apoptotic homologues |
HPV E6 and E7 attack exactly the two checkpoints that sporadic cancers mutate, which is why a virus can substitute for years of accumulated mutation.
Burkitt lymphoma carries the t(8;14) translocation placing MYC under immunoglobulin heavy chain control, and its endemic African form is jaw-centred while the sporadic form is abdominal.
8. Herpesviruses and latency
The defining property of the family is lifelong latency with reactivation under immunosuppression.
| Virus | Latency site | Reactivation disease |
|---|---|---|
| HSV-1 and HSV-2 | Sensory ganglia | Cold sores, genital recurrence |
| VZV | Dorsal root ganglia | Herpes zoster |
| EBV | B lymphocytes | Post-transplant lymphoproliferative disease |
| CMV | Monocytes | Retinitis, colitis, pneumonitis |
CMV is the commonest congenital viral infection, and its classic findings are periventricular calcification and sensorineural deafness.
Toxoplasma calcification is scattered while CMV calcification is periventricular, and that single contrast resolves most congenital infection stems.
Owl's eye intranuclear inclusions identify CMV; Cowdry type A inclusions and multinucleated giant cells on a Tzanck smear identify HSV and VZV.
9. Diagnosis and antivirals
Choosing the test follows from the stage of illness.
| Situation | Best test |
|---|---|
| Early acute infection | PCR or antigen detection |
| Retrospective diagnosis | Paired sera showing fourfold antibody rise |
| Recent infection | IgM |
| Past exposure or immunity | IgG |
| Treatment monitoring | Quantitative viral load |
Acyclovir requires viral thymidine kinase for its first phosphorylation, which is why it is selective for HSV and VZV and why thymidine kinase mutation is the commonest resistance mechanism.
Ganciclovir covers CMV, which lacks thymidine kinase but supplies the UL97 kinase instead, and its dose-limiting toxicity is myelosuppression.
Foscarnet needs no activation at all, so it works against thymidine-kinase-mutant resistant strains, at the cost of nephrotoxicity.
10. Worked examples
Example 1. A man has HBsAg negative, anti-HBs negative, IgM anti-HBc positive. What is the interpretation?
Work through the timeline. HBsAg has already cleared, anti-HBs has not yet appeared, and only IgM anti-HBc is present. This is the window period of acute hepatitis B, and the patient is still infectious.
Example 2. A child is bitten on the cheek by a stray dog, with bleeding. What is required?
Bleeding through the skin makes this category III, so wound washing, vaccination and local infiltration of rabies immunoglobulin are all required. The facial site shortens the incubation period, making immediate action more urgent, not less.
Example 3. An HIV-positive man with CD4 of 40 has floaters and painless visual loss. What is the diagnosis?
A CD4 below 50 with retinal findings points to CMV retinitis. Below 200 would suggest Pneumocystis and below 100 cryptococcal or toxoplasma disease, so the count itself narrows the answer before the eye findings are considered.
Summary
Sort every virus by genome and envelope first, because those two properties predict replication site, mutation rate, transmission route and disinfection before any species fact is recalled.
DNA viruses replicate in the nucleus with proofreading and mutate slowly, so their vaccines last; RNA viruses replicate in the cytoplasm without proofreading and mutate fast.
Segmentation permits reassortment, which is why only influenza A causes pandemics and why drift and shift are different in kind rather than degree.
Read hepatitis B serology as a timeline: HBsAg first, IgM anti-HBc through the window, anti-HBs last, and any anti-HBc proves natural infection rather than vaccination.
Hepatitis E is the pregnancy virus, with third-trimester mortality near twenty per cent, and the commonest cause of epidemic waterborne jaundice in India.
In HIV, CD4 count predicts the opportunistic infection, with tuberculosis the Indian exception occurring at any count, and infants need DNA PCR because maternal antibody persists.
TLD is India's first-line regimen, treatment starts at diagnosis regardless of CD4, and viral load rather than CD4 monitors response.
Rabies is judged only by exposure category, immunoglobulin is infiltrated locally rather than given systemically, and the intradermal schedule is two sites on days 0, 3, 7 and 28.
Oncogenic viruses each disable a specific checkpoint, and HPV E6 and E7 attack p53 and RB directly, which is why one virus can do the work of years of mutation.
Herpesviruses are defined by latency, and reactivation site predicts the disease, with periventricular calcification separating congenital CMV from scattered toxoplasma calcification.
