Topic 5: Virology — General Concepts, DNA & RNA Viruses
Introduction
Viruses are obligate intracellular parasites that cannot replicate independently — they require host cell machinery to reproduce. Viruses cause a significant proportion of human infectious diseases, ranging from the common cold to AIDS, hepatitis, encephalitis, and emerging infections like COVID-19. For FMGE, understanding viral replication cycles, classification, and specific viral pathogens is essential.
General Properties of Viruses
- Size: 20–300 nm (much smaller than bacteria)
- Nucleic acid: Either DNA or RNA — never both
- Protein coat (capsid): Composed of capsomeres; protects nucleic acid
- Symmetry: Icosahedral (e.g., poliovirus, adenovirus) or helical (e.g., rabies, tobacco mosaic virus)
- Envelope: Present in some viruses ( lipid bilayer derived from host cell membrane); viruses without envelopes are more resistant (e.g., adenovirus, poliovirus)
- No metabolism: No enzymes for energy production or protein synthesis — entirely dependent on host
Viral Replication — General Steps
- Attachment (Adsorption): Viral surface proteins (hemagglutinin in influenza; gp120 in HIV) bind to specific host cell receptors
- Penetration: Receptor-mediated endocytosis (non-enveloped viruses) or membrane fusion (enveloped viruses)
- Uncoating: Capsid removed; viral nucleic acid released into cytoplasm/nucleus
- Replication: Viral genome replicates; viral mRNA and proteins synthesized using host machinery
- Assembly (Maturation): New virions assembled
- Release: Budding (enveloped viruses) or cell lysis (non-enveloped viruses)
Viral Classification (Baltimore Classification)
| Class | Genome | Example |
|---|---|---|
| I | dsDNA | Herpesvirus, Adenovirus |
| II | ssDNA (positive sense) | Parvovirus |
| III | dsRNA | Rotavirus |
| IV | ssRNA (+) sense | Poliovirus, Hepatitis A, SARS-CoV-2 |
| V | ssRNA (−) sense | Influenza, Rabies, Measles |
| VI | ssRNA (+) → DNA (reverse transcriptase) | HIV (Retrovirus) |
| VII | dsDNA → RNA (reverse transcriptase) | Hepatitis B (Hepadnavirus) |
Important DNA Viruses
Herpesviruses (Family: Herpesviridae)
All herpesviruses are large, enveloped, dsDNA viruses. They establish latency after primary infection and can reactivate periodically.
- Herpes simplex virus type 1 (HSV-1) — oral herpes; cold sores; also causes herpes simplex encephalitis (temporal lobe involvement)
- Herpes simplex virus type 2 (HSV-2) — genital herpes; vesicular lesions on erythematous base
- Varicella-zoster virus (VZV) — chickenpox (varicella — primary infection); shingles (zoster — reactivation along dermatome); Tzanck smear shows multinucleated giant cells
- Cytomegalovirus (CMV) — congenital infections (periventricular calcifications, hearing loss, hepatosplenomegaly); mononucleosis-like syndrome in immunocompromised; owl’s eye intranuclear inclusion bodies
- Epstein-Barr virus (EBV) — infectious mononucleosis (fatigue, pharyngitis, lymphadenopathy — especially posterior cervical); Downey cells (atypical lymphocytes); associated with Burkitt lymphoma (endemic, jaw involvement in African children) and nasopharyngeal carcinoma
Hepatitis Viruses
| Virus | Genome | Transmission | Chronic Risk | Vaccine |
|---|---|---|---|---|
| Hepatitis A | ssRNA (+) | Fecal-oral | No chronic | Yes |
| Hepatitis B | dsDNA (partially) | Blood, sexual, perinatal | Yes (10%) | Yes |
| Hepatitis C | ssRNA (+) | Blood | Yes (80%) | No |
| Hepatitis E | ssRNA (+) | Fecal-oral | No (except preg.) | No (in India) |
Hepatitis B serology:
- HBsAg: Surface antigen — indicates active infection
- Anti-HBs: Surface antibody — indicates immunity (infection recovery or vaccination)
- HBcAg: Core antigen — not detectable in serum
- Anti-HBc (IgM): Acute/recent infection
- Anti-HBc (IgG): Past infection or chronic
- HBeAg: Viral replication marker — high infectivity
Hepatitis B vaccine — contains recombinant HBsAg; 3-dose schedule (0, 1, 6 months); protective antibody level ≥10 mIU/mL
Important RNA Viruses
Orthomyxoviridae — Influenza Virus
Segmented, negative-sense, single-stranded RNA virus with envelope; hemagglutinin (HA) mediates attachment and entry; neuraminidase (NA) cleaves sialic acid for release of new virions.
- Antigenic drift — minor mutations in HA/NA; causes seasonal epidemics
- Antigenic shift — major reassortment of genome segments (especially in avian/human strains); causes pandemics (e.g., H1N1 2009)
Laboratory diagnosis: Nasopharyngeal swab → RT-PCR (gold standard); rapid antigen detection; viral culture in MDCK cells
Treatment: Oseltamivir, zanamivir (neuraminidase inhibitors); amantadine/rimantadine (M2 inhibitors — no longer recommended due to resistance)
Paramyxoviruses
- Measles virus — Koplik spots (pathognomonic), maculopapular rash (head to toe), conjunctivitis, cough, coryza (3 Cs); giant cell pneumonia, subacute sclerosing panencephalitis (SSPE); inactivated measles vaccine caused atypical measles
- Mumps virus — parotitis (bilateral); aseptic meningitis, orchitis, pancreatitis
- Respiratory syncytial virus (RSV) — major cause of bronchiolitis in infants; syncytial giant cells in respiratory epithelium
- Human metapneumovirus — acute respiratory tract infections in children
Rhabdoviridae — Rabies Virus
Bullet-shaped, negative-sense ssRNA virus; Negri bodies (intracytoplasmic inclusion bodies) in neurons — pathognomonic for rabies; transmitted via animal bite (dog is main reservoir in India)
Clinical stages: Prodrome (fever, paresthesia at bite site) → Excitative phase (hydrophobia, aerophobia, agitation, hypersalivation) → Coma → Death
Post-exposure prophylaxis (PEP): Wound cleaning + rabies immunoglobulin (RIG — infiltrated around wound) + rabies vaccine (day 0, 3, 7, 14, 28 — Zagreb 2-1-1 regimen or standard 5-dose Essen)
HIV (Human Immunodeficiency Virus)
Retrovirus (ssRNA → reverse transcriptase → dsDNA → integration into host genome)
Structure: Enveloped; two copies of gp120/gp41 on surface (receptor binding); p24 capsid protein (diagnostic marker); reverse transcriptase, integrase, protease
Transmission: Blood, sexual contact, perinatal; CD4+ T lymphocytes are primary target (CD4 is the receptor)
Opportunistic infections (AIDS-defining):
- Pneumocystis jirovecii pneumonia (PJP) — most common AIDS-defining illness; ground-glass appearance on chest X-ray; diagnosis by BAL with methenamine silver stain
- Oesophageal candidiasis — white plaques
- Cryptococcal meningitis — India ink negative stain of CSF
- Toxoplasma encephalitis — ring-enhancing brain lesions
- Cryptosporidium — watery diarrhea
Diagnosis: ELISA (screening) → Western blot (confirmation); now replaced by rapid immunochromatographic tests; CD4 count for staging and treatment decisions
Treatment (ART — Antiretroviral Therapy): HAART (Highly Active ART) — combination of at least 3 drugs:
- NRTIs (Zidovudine, Tenofovir, Lamivudine)
- NNRTIs (Efavirenz, Nevirapine)
- Protease inhibitors (Ritonavir, Lopinavir)
- Integrase inhibitors (Raltegravir, Dolutegravir)
FMGE High-Yield Points
- HSV-1 = oral; HSV-2 = genital; VZV = chickenpox/shingles; CMV = congenital CMV (owl’s eye inclusions); EBV = infectious mono (Downey cells) + Burkitt lymphoma
- Hepatitis B serology: HBsAg positive + Anti-HBs negative = acute/chronic infection
- HBsAg positive + HBeAg positive = high infectivity
- Influenza = segmented, negative-sense RNA; antigenic drift (epidemic) vs. shift (pandemic)
- Rabies = Negri bodies; hydrophobia; PEP with vaccine + immunoglobulin
- HIV = CD4+ T cell destruction; PJP most common AIDS-defining illness; CD4 <200 = start prophylaxis for PJP, toxoplasma, MAC
- Rotavirus = most common cause of severe childhood diarrhea globally; double-shelled wheel appearance on EM; oral rehydration is cornerstone of treatment
⚡ Exam tip: A child with acute watery diarrhea, dehydration, and characteristic “wheel-like” virus particles on electron microscopy = rotavirus gastroenteritis. Supportive care + ORS is the treatment.