Learn — Virology

7 notes · 26 questions on the topic

Viral families classification

Viruses are classified by the nucleic acid they carry (DNA or RNA), by whether that genome is single- or double-stranded, by the presence or absence of a lipid envelope, and by capsid symmetry and virion size. The scheme is not academic: the genome tells you which antiviral class can work, and the envelope tells you how easily the virus is killed on a ward surface and on the nurse's hands.

The medically important DNA families are Herpesviridae (herpes simplex, varicella-zoster, cytomegalovirus, Epstein-Barr, human herpesvirus 6 and 8), Poxviridae (smallpox, monkeypox, molluscum), Adenoviridae, Papillomaviridae, Polyomaviridae, Parvoviridae (B19) and Hepadnaviridae (hepatitis B).
The medically important RNA families include Picornaviridae (polio, coxsackie, rhinovirus, hepatitis A), Retroviridae (HIV, HTLV), Orthomyxoviridae (influenza), Paramyxoviridae (measles, mumps, parainfluenza, respiratory syncytial virus), Rhabdoviridae (rabies), Flaviviridae (dengue, Japanese encephalitis, yellow fever, Zika, hepatitis C), Togaviridae (rubella, chikungunya), Coronaviridae, Caliciviridae (norovirus), Reoviridae (rotavirus), Filoviridae (Ebola, Marburg) and Hepeviridae (hepatitis E).
All DNA viruses are double-stranded except the parvoviruses, and all RNA viruses are single-stranded except the reoviruses including rotavirus; these are the two exceptions the paper asks for again and again.
DNA viruses replicate in the nucleus except the poxviruses, and RNA viruses replicate in the cytoplasm except the orthomyxoviruses and the retroviruses.
An enveloped virus carries a host-derived lipid bilayer and is destroyed by soap, alcohol-based hand rub, detergents, drying, heat and bile; a naked virus has only a protein capsid, survives for days on surfaces, passes the stomach intact and resists alcohol. The naked viruses are the faecal-oral ones: polio, hepatitis A, hepatitis E, rotavirus, norovirus and adenovirus.
The bedside consequence is direct: after caring for a patient with rotavirus, norovirus or hepatitis A, alcohol rub is not enough, so hands are washed with soap and running water and surfaces are cleaned with 1 percent sodium hypochlorite.
A segmented genome permits reassortment and therefore antigenic shift, which is why influenza with its 8 segments and rotavirus with its 11 produce new strains and pandemics, while point mutation alone (antigenic drift) explains the yearly influenza change.
Only three viruses drive the sharps policy because they are transmitted by blood and body fluid: hepatitis B, hepatitis C and HIV. Airborne spread is limited to measles and varicella, and to SARS-CoV-2 during aerosol-generating procedures, while the rest of the respiratory group spreads by droplets.

Hepatitis viruses (A-E)

The hepatitis viruses A to E are five unrelated viruses that share one target, the hepatocyte, and are separated by their route of spread and their capacity to become chronic. A and E are naked viruses spread by the faecal-oral route and cause acute self-limiting illness, while B, C and D are blood-borne and cause chronic hepatitis, cirrhosis and hepatocellular carcinoma, which is why they are the ones that matter after a needle-stick injury.

Hepatitis A is a naked RNA picornavirus with an incubation period of about 15 to 50 days, spread by contaminated food and water; it never becomes chronic, is diagnosed by anti-HAV IgM, and is preventable by a vaccine that is not part of India's Universal Immunisation Programme.
Hepatitis B is a DNA hepadnavirus with a long incubation period of about 30 to 180 days, spread by blood, sexual contact and perinatal transmission; infection acquired at birth becomes chronic in the great majority of babies, while infection acquired in adult life becomes chronic in only a small minority.
Hepatitis B serology in order: HBsAg is the first marker to appear and its persistence beyond 6 months defines chronic infection, anti-HBc IgM is the only marker present in the window period after HBsAg has gone and before anti-HBs appears, HBeAg means active replication and high infectivity, anti-HBs alone means vaccine-induced immunity, and anti-HBs with anti-HBc means recovered natural infection.
India gives hepatitis B vaccine as a birth dose within 24 hours of delivery followed by the pentavalent doses at 6, 10 and 14 weeks; a baby born to an HBsAg-positive mother also receives hepatitis B immunoglobulin, and the birth dose is never postponed.
Hepatitis C is an RNA flavivirus spread by blood through unsafe injections, unscreened transfusion and injecting drug use, and it becomes chronic in most of those infected; there is no vaccine, but direct-acting antiviral tablets cure the great majority and testing and treatment are free under India's National Viral Hepatitis Control Programme.
Hepatitis D is a defective RNA virus that needs the hepatitis B surface antigen to assemble, so it occurs only as co-infection with acute hepatitis B or as superinfection of a chronic carrier; superinfection is the more dangerous of the two, and hepatitis B vaccine prevents both.
Hepatitis E is a naked RNA virus spread by faecally contaminated drinking water, causes large monsoon and post-flood outbreaks in India, and carries a very high case fatality from fulminant hepatic failure in the third trimester of pregnancy, which is the single most examined fact in this note.
Precautions follow the route: hepatitis A and E need standard precautions with scrupulous hand washing and safe disposal of stool, with contact precautions for an incontinent or nappied patient, while hepatitis B, C and D need standard precautions with strict sharps discipline, no recapping, a needle destroyer at the point of use, and white translucent puncture-proof containers under the Biomedical Waste Management Rules 2016.

Epstein-Barr virus

Epstein-Barr virus (human herpesvirus 4) is an enveloped DNA herpesvirus that enters B lymphocytes through the CD21 complement receptor and then persists in them for life. It causes infectious mononucleosis, the triad of fever, exudative pharyngitis and generalised lymphadenopathy in an adolescent, and it matters at the bedside because the enlarged spleen can rupture and because the pharyngitis is routinely mistaken for streptococcal sore throat and given ampicillin.

Transmission is by saliva through shared cups and spoons and by kissing, hence the popular name, and the incubation period is about 4 to 6 weeks, far longer than that of the common childhood exanthems.
The classical picture is fever, a sore throat with grey-white exudative or membranous tonsillitis, tender posterior cervical and generalised lymphadenopathy, profound fatigue, splenomegaly in about half of patients and hepatomegaly with mild transaminitis; periorbital oedema and palatal petechiae support the diagnosis.
The blood picture is an absolute lymphocytosis with more than 10 percent atypical lymphocytes (Downey cells), which are reactive T lymphocytes and not the infected B cells.
The screening test is the heterophile antibody test (Paul-Bunnell, or the Monospot slide test), which detects antibody agglutinating sheep or horse red cells; it may be negative in the first week and is negative in a large proportion of children under 4 years, so a negative result in a typical case is followed by EBV-specific serology, in which viral capsid antigen IgM means current infection and antibody to the nuclear antigen means past infection.
Ampicillin or amoxicillin given for the sore throat produces a florid non-allergic maculopapular rash in a high proportion of patients with infectious mononucleosis; this is the classic examination question, and it must not be recorded as a penicillin allergy.
Splenic rupture is the emergency complication, usually in the second or third week and often after trivial trauma, so contact sports, gym work, heavy lifting and vigorous abdominal palpation are avoided for at least 3 to 4 weeks and until the splenomegaly has settled.
Epstein-Barr virus is oncogenic and is linked to Burkitt lymphoma (the African jaw tumour), nasopharyngeal carcinoma, Hodgkin lymphoma, post-transplant lymphoproliferative disease and oral hairy leukoplakia in advanced HIV.
Management is supportive with rest, fluids, paracetamol and saline gargles under standard precautions with no isolation needed; corticosteroids are reserved for airway obstruction from tonsillar enlargement, haemolytic anaemia or severe thrombocytopenia, and aspirin is avoided in children because of Reye syndrome.

Mumps

Mumps is an acute systemic infection by an enveloped single-stranded RNA paramyxovirus whose hallmark is painful non-suppurative swelling of one or both parotid glands. It matters because the virus does not stay in the parotid but also seeds the meninges, testis, ovary, pancreas and eighth cranial nerve, and because it spreads through hostels, schools and wards before anyone has made the diagnosis.

Spread is by respiratory droplets and saliva-contaminated articles, the incubation period is 16 to 18 days with a range of about 12 to 25 days, and the patient is infectious from roughly 2 days before the swelling appears until 5 days after it.
Parotitis is bilateral in most cases, pushes the ear lobe upwards and outwards, obliterates the angle of the jaw, is made worse by sour food, and is accompanied by redness and swelling at the opening of the parotid duct with no pus expressible from it.
The complications are what the examiner asks for: aseptic meningitis is the commonest, orchitis occurs in post-pubertal males and is usually unilateral with sterility rare, and mumps is a classic cause of acquired unilateral sensorineural deafness in children; oophoritis, pancreatitis and encephalitis also occur, and orchitis or meningitis can appear with no parotid swelling at all.
Diagnosis is clinical and is confirmed by mumps-specific IgM serology or by RT-PCR on a buccal or throat swab, saliva or urine; serum amylase is raised from the salivary gland rather than the pancreas in uncomplicated parotitis.
Isolation is droplet precautions in a single room for 5 days after the onset of parotid swelling, with a surgical mask for anyone entering and for the patient during transport, and the case is reported so that contacts and ward immunisation status can be checked.
Prevention is the live attenuated mumps component of MMR given as two doses; the Indian point that is examined is that MMR is not part of the Universal Immunisation Programme, which carries measles-rubella vaccine only, so mumps cover depends on private or state-programme vaccination. Live vaccine is contraindicated in pregnancy and in significant immunosuppression.

HIV — virus structure

HIV is an enveloped retrovirus of the lentivirus group that carries two identical copies of positive-sense single-stranded RNA together with its own reverse transcriptase, integrase and protease. Its structure is its clinical behaviour: gp120 binds CD4, reverse transcriptase makes the DNA copy that integrates for life, and each of the three enzymes is the target of one class of antiretroviral drug.

The envelope is host cell membrane studded with the glycoprotein spike gp160, cleaved into gp120, the knob that binds CD4, and gp41, the stalk that fuses the viral and cell membranes; because that envelope is lipid, HIV is destroyed rapidly by soap, alcohol, hypochlorite, heat and drying and does not survive on ward surfaces.
Beneath the envelope lie the p17 matrix and the cone-shaped p24 capsid, and p24 is the antigen that appears earliest in blood and forms the antigen half of a fourth-generation antigen-antibody combination test.
The core holds the two RNA copies with nucleocapsid protein p7 plus reverse transcriptase, an RNA-dependent DNA polymerase with no proofreading (which is why the virus mutates and why resistance emerges), integrase and protease.
The three structural genes are gag for the core proteins, pol for the enzymes and env for gp120 and gp41, with the regulatory genes tat, rev, nef, vif, vpr and vpu; the drug classes map straight onto them as nucleoside and non-nucleoside reverse transcriptase inhibitors, integrase inhibitors and protease inhibitors.
The receptor is CD4 with a chemokine co-receptor, CCR5 for the macrophage-tropic strains transmitted early and CXCR4 for the T-cell-tropic strains later; the CD4 T lymphocyte is progressively destroyed, which is why the CD4 count measures immune damage while the viral load measures how much virus is being made.
HIV-1 causes the global pandemic while HIV-2 is largely confined to West Africa, progresses more slowly, gives lower viral loads and is naturally resistant to the non-nucleoside reverse transcriptase inhibitors, so the two must be distinguished before treatment is chosen.
The diagnostic window follows the structure: viral RNA becomes detectable at about 10 days, p24 antigen at around 2 weeks and antibody by a third-generation assay at about 3 to 4 weeks, with a repeat test advised to close the window period. India's strategy for diagnosing an asymptomatic person is three tests using different antigen preparations or principles, all reactive, performed with pre-test and post-test counselling at an integrated counselling and testing centre.
A baby born to a mother with HIV carries maternal antibody for up to 18 months, so antibody tests cannot diagnose infection in infancy and early infant diagnosis uses HIV DNA or RNA polymerase chain reaction from about 6 weeks of age.

HPV

Human papillomavirus is a small naked double-stranded DNA virus that infects squamous epithelium and is the necessary cause of cervical cancer, one of the commonest cancers in Indian women. Most infections clear on their own within about two years, and it is persistent infection with a high-risk genotype that drives the slow progression from cervical intraepithelial neoplasia to invasive cancer over one to two decades, which is precisely the window that vaccination and screening exploit.

Transmission is by skin-to-skin and mucosal contact, chiefly sexual; condoms reduce but do not abolish the risk because the virus also infects skin outside the covered area, and perinatal transmission causes juvenile recurrent respiratory papillomatosis.
The high-risk oncogenic genotypes are 16 and 18, which together cause about 70 percent of cervical cancers, with 31, 33, 45, 52 and 58 accounting for much of the remainder, while the low-risk types 6 and 11 cause about 90 percent of anogenital warts and are not oncogenic.
The mechanism is viral integration with over-expression of the E6 and E7 oncoproteins, which inactivate the p53 and retinoblastoma tumour suppressor proteins respectively, and this is the single most examined molecular fact about the virus.
The same virus causes cancer of the vulva, vagina, penis, anus and oropharynx, so vaccination protects boys as well as girls.
Vaccination is given before sexual debut, ideally at 9 to 14 years: WHO recommends two doses at 0 and 6 months for that age group and has accepted a single-dose alternative schedule, while three doses are used for those starting at 15 years and above and for immunocompromised and HIV-positive girls. Bivalent, quadrivalent, nonavalent and the Indian-made quadrivalent products are available.
Screening looks for the silent pre-cancer, not for symptoms: WHO now recommends HPV DNA testing as the preferred primary screening test from 30 years of age, while India's programme screens women aged 30 to 65 by visual inspection with acetic acid at Ayushman Arogya Mandirs (formerly health and wellness centres), with cytology and colposcopy as the referral steps.
Vaccination does not replace screening, because the vaccines do not cover every oncogenic type and do not clear an infection that is already present, so a vaccinated woman still enters the screening programme at 30.

Rotavirus

Rotavirus is a naked, wheel-shaped virus with a segmented double-stranded RNA genome and is the commonest cause of severe dehydrating diarrhoea in children under 5 years. It matters because the child dies not of the virus but of the fluid and electrolyte loss, and because a naked virus survives on cots, toys and hands long enough to cause ward outbreaks.

Spread is faecal-oral through hands, surfaces, water and food, the incubation period is short at about 1 to 3 days, the infecting dose is tiny and the virus is shed in enormous numbers.
The virus destroys the mature enterocytes at the tips of the small intestinal villi and its NSP4 protein acts as an enterotoxin, so the diarrhoea is both osmotic, with secondary lactose intolerance from lost disaccharidases, and secretory; the stool is watery and non-bloody with vomiting and low-grade fever and contains no blood or pus cells.
Diagnosis is by detecting viral antigen in stool with an enzyme immunoassay or latex agglutination; electron microscopy shows the classical wheel-like particle and gel electrophoresis shows the 11 genome segments, but treatment never waits for any of it.
Treatment is fluid rather than antiviral or antibiotic: assess the degree of dehydration and follow WHO Plan A, B or C, using low-osmolarity oral rehydration solution for some dehydration and intravenous Ringer lactate for severe dehydration, with zinc for 14 days (20 mg daily, 10 mg under 6 months) and continued breastfeeding throughout.
Rotavirus vaccine is part of India's Universal Immunisation Programme as an oral liquid given with the pentavalent doses at 6, 10 and 14 weeks; it is a live vaccine, the course must start in early infancy, and previous intussusception or severe combined immunodeficiency is a contraindication.
Because rotavirus is a naked virus, alcohol-based hand rub is unreliable against it, so hands are washed with soap and running water, cots and surfaces are cleaned with 1 percent sodium hypochlorite, and the child is nursed with contact precautions and dedicated equipment rather than the droplet precautions the older notes describe.
Beyond the vaccine, prevention is exclusive breastfeeding for the first 6 months, safe drinking water, hand washing after nappy changes and safe disposal of children's stools.

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