General Properties of Viruses and Virus-Host Interaction

What Makes Viruses Different

Obligate intracellular. One nucleic acid type only (DNA or RNA, never both). Filterable (smaller than bacteria). No cell-free growth — needs living cell/embryonated egg. No cell wall/membrane/organelles/ribosomes. Replicate by complex assembly, not binary fission. Not affected by antibacterial antibiotics.

Structure

Virion = nucleic acid + capsid (protein coat, made of capsomeres) = nucleocapsid.

Capsid functions: protects nucleic acid, mediates attachment (non-enveloped viruses), antigenic.

Envelope: lipoprotein, lipid from host membrane, protein (peplomers/spikes) virus-coded. Peplomers = antigenic + receptor binding (e.g. influenza HA/NA). Enveloped viruses — susceptible to heat/ether.

Non-enveloped exceptions: DNA — parvovirus, adenovirus, papovavirus. RNA — picornavirus, reovirus, calicivirus, HAV, HEV.

Symmetry: Icosahedral (rigid, most DNA viruses except pox, most RNA viruses). Helical (flexible, myxo/rhabdo/filo/bunyaviruses). Complex (poxvirus only).

Size: 20nm (parvovirus, smallest) – 400nm (poxvirus, largest).

Shapes: Rabies = bullet. Ebola = filamentous. Poxvirus = brick. Adenovirus = space-vehicle. Rotavirus = wheel.

Viroids: naked circular ssRNA, no capsid, plants (HDV similar in humans). Prions: infectious protein, no nucleic acid, highly resistant, cause spongiform encephalopathy.

Classification

Family (-viridae) by nucleic acid/envelope/symmetry/replication. Genus (-virus) by physicochemical/serological differences.

Most DNA = dsDNA (except parvovirus = ssDNA). Most RNA = ssRNA (except reovirus = dsRNA, retrovirus = 2 copies ssRNA).

Segmented genome: Influenza, Rotavirus, Bunyavirus, Arenavirus (enables reassortment).

Viral Replication — 7 steps

Attachment → Penetration → Uncoating → Biosynthesis → Assembly → Maturation → Release

Attachment: receptor-specific (HIV gp120–CD4; Influenza HA–respiratory epithelium receptor).

Penetration: Phagocytosis/viropexis (endocytosis) / Membrane fusion (enveloped, e.g. HIV) / Injection of nucleic acid only (bacteriophage).

Uncoating: capsid removed by lysosomal enzymes. Absent in bacteriophages (no capsid entered).

Biosynthesis by type:

• DNA viruses: DNA replication in nucleus (except pox = cytoplasm). Early mRNA/proteins → shut host metabolism, replicate DNA → late mRNA/proteins → structural proteins.
• +ve sense ssRNA: directly translated (acts as mRNA) → early proteins have RNA polymerase → (+)→(−)→(+) ssRNA cycle
• −ve sense ssRNA (myxovirus, rabies): cannot translate directly → viral RNA polymerase makes (+)ssRNA first → mRNA + template for (−)ssRNA
• dsRNA (reovirus/rotavirus): (+) strand = mRNA directly; both strands template duplex synthesis
• Retrovirus (HIV): 2 copies (+)ssRNA + reverse transcriptase + integrase. RT: RNA→DNA:RNA hybrid → RNase activity digests RNA → dsDNA → nucleus → integrase inserts into host chromosome → template for mRNA + genomic RNA

Assembly: nucleus (DNA viruses, except hepadnavirus/pox = cytoplasm); cytoplasm (RNA viruses).

Maturation: nucleus/cytoplasm/membranes (Golgi, ER, plasma membrane).

Release: Lysis (non-enveloped + phages) OR Budding (enveloped — acquires envelope + inserts glycoproteins).

Eclipse phase: penetration → first infectious progeny. Phage: 15-30 min. Animal virus: 15-30 hr.

Defective viruses (need helper virus): Hepatitis D (needs HBV), Adeno-associated satellite virus (needs adenovirus).

Genetic Variation

Mutation: 10⁻⁴–10⁻⁸/base pair/generation.

Conditional lethal mutant — grows only in permissive conditions. Temperature-sensitive (ts) mutant — grows at low temp (28-31°C) not 37°C — used for live vaccines.

Genetic recombination — 2 related viruses, same cell → exchange segments → stable hybrid.

Reassortment — segmented RNA viruses (influenza, rota, bunya, arena) — whole segment exchange. Mechanism of influenza antigenic shift/pandemics (e.g. 2009 H1N1).

Viral interference — one virus suppresses another in same cell. Used in OPV (vaccine strains interfere with wild poliovirus spread).

Pathogenesis

Transmission → Primary site replication → Spread to secondary site → Disease manifestation.

Routes: respiratory (most common), oral, cutaneous, vector bite, animal bite, sexual, transfusion/injection, transplacental, conjunctival.

Local infection only (no viremia, short incubation, short immunity) OR spreads via lymphatics/blood (poliovirus)/neurons (rabies — no viremia).

Primary viremia → secondary site (RE system: bone marrow, spleen, liver, endothelium) → secondary viremia (nonspecific symptoms) → target organ (via tropism = receptor presence).

Incubation period ∝ distance from entry to target organ generally, but exceptions exist (dengue vs HBV — both blood-borne, very different incubation).

Manifestations depend on target: Respiratory (influenza, coronavirus), GI (rotavirus, norovirus), Hemorrhagic fever (dengue, Ebola), Meningitis/encephalitis (enterovirus, rabies, JE), Exanthem (measles, VZV), Hepatitis (hepatitis viruses).

Cellular-level Outcomes

1. Abortive infection — non-permissive cell, replication fails
2. Cytocidal/lytic infection — cell dies. Mechanisms: host DNA/protein synthesis inhibition; syncytium formation (paramyxo/herpes/retrovirus — cell-cell spread, escapes antibody); immune-mediated lysis (Ab+complement or NK cell)
3. Infection without cell death:
   • Steady state — coexistence, independent replication
   • Persistent infection — latency+reactivation (Herpesviridae); cell transformation (oncogenic viruses — HBV, EBV, HPV); HIV latency (integrated provirus); slow virus infection (long incubation); persistent tolerant infection (no immune response, e.g. LCMV in mice)

Inclusion bodies: Intracytoplasmic (acidophilic, pink) — Negri bodies (rabies), Guarnieri bodies (vaccinia). Intranuclear (basophilic) — Cowdry type A (variable/granular — YFV, HSV), Cowdry type B (small/circumscribed — poliovirus, adenovirus). Both — Owl’s eye (CMV).

Laboratory Diagnosis

Direct: EM, immuno-EM, fluorescent microscopy (direct-IF), light microscopy (inclusion bodies).

Antigen detection: ELISA/ICT — HBsAg (HBV), NS1 (dengue), nucleocapsid Ag (SARS-CoV-2), p24 (HIV).

Antibody detection: IgM or 4-fold IgG rise = recent infection. Stable IgG = past/chronic.

Molecular: PCR (DNA), RT-PCR (RNA), multiplex PCR (syndrome panel), real-time PCR (gold standard, quantifies viral load — monitors HIV/HBV treatment).

Virus isolation: Animal inoculation (research mostly), Egg inoculation (largely obsolete), Tissue culture (only routine method).

Cell line types:

• Primary — normal, fresh, 5-10 divisions, diploid (monkey kidney, chick embryo)
• Secondary/diploid — normal, 10-50 divisions, diploid (human fibroblast for CMV; MRC-5/WI-38 for vaccines/HSV)
• Continuous — cancer-derived, immortal, altered chromosome (HeLa, HEp-2, Vero, BHK) — most widely used

CPE (cytopathic effect) types: syncytium (measles/RSV/HSV), rapid degeneration (enteroviruses), grape-clump (adenovirus).

Treatment and Prophylaxis

Antivirals target virus-specific steps (DNA polymerase, neuraminidase, protease) without host toxicity. Limited to few diseases (herpesviruses, influenza, hepatitis).

Interferons (IFN-α, β): innate immunity, act indirectly (induce host antiviral proteins), fast (hours), no memory, non-specific. Uses: topical (rhinovirus, warts, keratitis) and systemic (chronic hepatitis B/C/D) + anticancer/autoimmune.

Vaccines:

• Killed — stable, safe in immunodeficiency/pregnancy, more reactogenic, usually multi-dose
• Live attenuated — strong durable immunity, single dose, risky in immunodeficiency/pregnancy, less stable
• Subunit — recombinant DNA tech, specific antigen only (HBsAg, HPV L1), fewer side effects

Passive immunization (immunoglobulin): immediate but temporary, no memory. For immunodeficient/post-exposure.

Combined immunization (vaccine + Ig together): Hepatitis B (HBsAg+ mother’s neonate), Rabies (class III bite).

What Sets Viruses Apart

Viruses are obligate intracellular parasites — the most primitive infectious agents of humans, and structurally the simplest. Several features distinguish them sharply from bacteria: a virus carries only one type of nucleic acid, ever, either DNA or RNA but never both; it is small enough to pass through filters that retain bacteria; it cannot be cultivated on any cell-free artificial medium, growing only inside a living cell (or, historically, in an embryonated egg); it has no cell wall, no cell membrane, and none of the organelles — including ribosomes — that a cell would use to synthesize its own proteins or nucleic acids; and it replicates by a complex multi-step assembly process rather than by binary fission. Because they depend entirely on host-cell machinery, viruses are also inherently unaffected by antibacterial antibiotics, which target bacterial structures viruses simply do not have.

Structure

The complete infectious viral particle is called a virion — nucleic acid enclosed in a protein coat, the capsid, built from repeating protein subunits called capsomeres. Together, nucleic acid plus capsid make up the nucleocapsid. The capsid is not passive packaging: it protects the genome from degradation, and in non-enveloped viruses it is the structure that actually attaches to host-cell receptors to initiate infection; it is also strongly antigenic and specific to the virus.

Many viruses carry a further outer layer, the envelope — lipoprotein in nature, with its lipid component stolen from the host cell membrane during release and its protein component (peplomers, projecting as surface spikes) coded by the virus itself. Peplomers can serve double duty: influenza’s hemagglutinin and neuraminidase spikes are both antigenic and directly involved in receptor binding and entry. Enveloped viruses are correspondingly more fragile — susceptible to heat and to lipid solvents such as ether — which is a practical basis for some disinfection strategies. Most viruses are enveloped; the notable non-enveloped exceptions are parvovirus, adenovirus, and papovavirus among DNA viruses, and picornavirus, reovirus, calicivirus, and hepatitis A and E viruses among RNA viruses.

Capsomere arrangement produces three symmetry patterns: icosahedral (cubical) symmetry, rigid and seen in nearly all DNA viruses except poxviruses and in most RNA viruses; helical symmetry, more flexible, seen in RNA viruses such as myxoviruses, rhabdoviruses, filoviruses, and bunyaviruses; and complex symmetry, unique to poxviruses, which fit neither pattern.

Size ranges from 20 nm (parvovirus, the smallest) to 400 nm (poxvirus, the largest) — small enough throughout this range that no virus can be resolved by ordinary light microscopy. Shape, too, is often distinctive enough to be diagnostic on electron microscopy: rabies virus is bullet-shaped, Ebola virus filamentous, poxvirus brick-shaped, adenovirus resembles a space vehicle, and rotavirus is wheel-shaped.

Viruses are not the only infectious particles smaller than bacteria. Viroids are naked, circular ssRNA with no capsid at all, mostly restricted to plant disease, though hepatitis D virus in humans is structurally similar. Prions are abnormal infectious protein molecules with no nucleic acid whatsoever, remarkably resistant to standard physical and chemical decontamination, and responsible for the neurodegenerative spongiform encephalopathies.

Classification

Viruses infecting humans are grouped into families (the suffix -viridae) by nucleic acid type, envelope status, symmetry, and replication strategy, and further split into genera (suffix -virus) by physicochemical or serological differences. The nucleic acid itself varies along several axes: most DNA viruses are double-stranded, with parvoviruses the single-stranded exception; most RNA viruses are single-stranded, with reoviruses (double-stranded) and retroviruses (two copies of single-stranded RNA) as the exceptions; and while most viral genomes are unsegmented, influenza virus, rotavirus, bunyaviruses, and arenaviruses carry their genome split across multiple RNA segments — a detail with real biological consequences, since segmented genomes are what make reassortment possible (see below).

Viral Replication

Unlike bacterial binary fission, viral replication proceeds through seven sequential steps: attachment → penetration → uncoating → biosynthesis → assembly → maturation → release.

Attachment is the first and most specific step, driven by receptor interactions — HIV’s gp120 envelope glycoprotein binds CD4 on the host cell; influenza’s hemagglutinin binds glycoprotein receptors on respiratory epithelium. Penetration follows by one of three routes: phagocytosis/viropexis (receptor-mediated endocytosis, taking the whole particle into an endosome), membrane fusion (enveloped viruses such as HIV fuse their envelope with the plasma membrane, releasing only the nucleocapsid into the cytoplasm while the envelope stays outside), or direct injection of nucleic acid alone, the strategy bacteriophages use since they cannot cross the rigid bacterial cell wall. Uncoating, mediated by host lysosomal enzymes, frees the nucleic acid from its capsid — a step that simply does not exist for bacteriophages, since only naked nucleic acid entered the cell in the first place.

Biosynthesis is where nucleic acid, capsid protein, replication enzymes, and regulatory proteins (which shut down host-cell metabolism to redirect resources toward the virus) are all synthesized. The site and detail of this step differ by nucleic-acid type:

• DNA viruses generally replicate DNA in the nucleus (poxviruses are the cytoplasmic exception) while mRNA transcription and translation happen in the cytoplasm regardless. An early round of transcription and translation produces non-structural proteins that shut down host metabolism and drive replication of the parental genome; a later round produces the structural proteins (capsid, envelope components) needed for assembly.
• Positive-sense ssRNA viruses carry RNA with the same polarity as mRNA, so it can be translated directly into early proteins immediately on entry; those early proteins include an RNA polymerase that then drives replication through a negative-sense intermediate back to progeny positive-sense RNA.
• Negative-sense ssRNA viruses (myxoviruses, rabies) carry RNA of the opposite polarity to mRNA and therefore cannot be translated directly — a virally supplied RNA polymerase must first transcribe it into positive-sense RNA, which then both serves as mRNA for translation and as the template for making more negative-sense genome copies.
• Double-stranded RNA viruses (reoviruses, e.g. rotavirus) use the positive strand of each segment as mRNA directly, while both strands together template synthesis of new duplex segments.
• Retroviruses carry two copies of positive-sense ssRNA plus their own reverse transcriptase and integrase. Reverse transcriptase first makes a DNA:RNA hybrid (RNA-dependent DNA polymerase activity), then digests away the RNA strand (a built-in ribonuclease activity of the same enzyme), then completes a double-stranded DNA copy; that DNA is transported into the nucleus and integrated into the host chromosome by viral integrase, after which it serves as a permanent template for both mRNA and fresh genomic RNA.

Assembly packages nucleic acid and protein into new nucleocapsids — in the nucleus for most DNA viruses (again excepting hepadnaviruses and poxviruses, assembled in the cytoplasm) and in the cytoplasm for RNA viruses. Maturation follows, in the nucleus, cytoplasm, or at internal membranes (Golgi, endoplasmic reticulum, plasma membrane) depending on the virus. Release happens either by lysing the host cell (non-enveloped viruses and bacteriophages) or by budding through a host membrane, which is how enveloped viruses acquire their lipid envelope and simultaneously insert their own glycoproteins into it.

The eclipse phase is the interval between penetration and the appearance of the first infectious progeny particle, during which the virus cannot be detected inside the cell at all — roughly 15–30 minutes for bacteriophages, but 15–30 hours for most animal viruses, reflecting the much greater complexity of the eukaryotic replication cycle.

Some viruses are genetically incomplete and cannot replicate alone — defective viruses such as hepatitis D virus (which requires hepatitis B virus as a helper) or adeno-associated satellite viruses (which require adenovirus).

Viral Genetic Variation

Mutation occurs in every viral infection, at a frequency of roughly 10⁻⁴ to 10⁻⁸ per base pair per generation, but only becomes clinically relevant when it changes something observable. Conditional lethal mutants grow only under specific permissive conditions and fail elsewhere; the temperature-sensitive mutant, which grows at a lower permissive temperature but not at 37°C, is exploited deliberately to make attenuated live vaccines.

When two related viruses infect the same cell simultaneously, further variation can arise through genetic recombination (exchange of nucleic-acid segments between two related viruses, producing a stable, replicating hybrid) or, specifically in segmented RNA viruses (influenza, rota-, bunya-, and arenaviruses), through reassortment — whole-segment exchange rather than recombination within a segment. Reassortment between influenza strains is the mechanism behind antigenic shift and is how pandemic influenza strains such as the 2009 H1N1 strain have arisen. A separate phenomenon, viral interference, occurs when infection with one virus suppresses growth of a second virus in the same cell — exploited deliberately in oral polio vaccination, where the vaccine strains outcompete and limit the spread of wild poliovirus.

Pathogenesis

Most viral infections follow a common arc: transmission → primary-site replication → spread to a secondary site → disease manifestation.

Transmission occurs by respiratory, oral, cutaneous, vector-bite, animal-bite, sexual, transfusion/injection, transplacental, or conjunctival routes, and the same virus’s typical route often predicts whether it stays local or disseminates — influenza stays largely respiratory, while measles, rubella, and varicella-zoster start respiratory but spread systemically. Some viruses cause purely local disease at the portal of entry with no viremia and a correspondingly short incubation period and short-lived immunity; most, however, establish a silent local infection first, then spread — via lymphatics to regional nodes, via blood (poliovirus), or via neurons directly to the CNS (rabies, bypassing viremia altogether).

Where viremia does occur, it typically happens in two waves: primary viremia carries virus from the initial site (or draining lymph nodes) into the bloodstream, from where it seeds the reticuloendothelial system — bone marrow, spleen, liver, vascular endothelium — as a secondary site of amplification; secondary viremia then spills a much larger load back into the blood, producing the nonspecific systemic symptoms (fever, malaise) of the acute illness, before the virus finally reaches its target organ (lung, brain, skin, liver) and produces organ-specific disease. Which organ that turns out to be is governed by tropism — the presence of the right host-cell receptor for that particular virus — which is why hepatitis viruses reliably produce hepatitis and not, say, meningitis.

Incubation period broadly tracks the distance the virus must travel from entry site to target organ — short for a virus like influenza that produces disease essentially where it entered, long for one like poliovirus or rabies virus that must reach the CNS — though this rule has real exceptions (dengue and hepatitis B are both blood-borne, yet their incubation periods differ by weeks, reflecting differences in host response and replication kinetics that distance alone doesn’t capture).

Clinically, an infection may stay inapparent (subclinical) or become apparent, and apparent infection can run an acute, subacute, or chronic course, with the specific pattern of symptoms dictated by which organ the virus targets — respiratory tract infection from influenza and coronaviruses, gastroenteritis from rotavirus and norovirus, hemorrhagic fever from dengue and Ebola, meningitis or encephalitis from neurotropic agents, exanthematous rash from measles and varicella-zoster, and hepatitis with jaundice from the hepatitis viruses.

Outcomes at the Cellular Level

A given host cell infected by a virus can end up in one of three states, depending on the virus and the cell:

• Abortive (failed) infection — the cell is non-permissive, lacking the receptors or intracellular machinery the virus needs, so replication simply cannot proceed.
• Cytocidal (lytic) infection — the cell dies. Mechanisms include direct shutdown of host DNA or protein synthesis, and syncytium formation, where viral glycoproteins expressed on the infected cell’s surface fuse it with neighbouring cells into a multinucleated giant cell — a strategy (used by paramyxoviruses, herpesviruses, and retroviruses) that lets the virus spread directly from cell to cell without ever being exposed to circulating antibody. Immune-mediated lysis is also possible, when viral antigens displayed on the cell surface trigger antibody-plus-complement or NK-cell killing of the infected cell itself.
• Infection without cell death — either a steady-state infection, where virus and host cell coexist and both replicate independently without injury (producing inapparent or mild apparent disease), or a persistent infection, which can itself take several forms: latency with periodic reactivation (the signature behaviour of the herpesvirus family); cell transformation, where an oncogenic virus (hepatitis B, EBV, HPV) drives the host cell to divide indefinitely, producing a tumour; the long clinical latency of HIV, where the integrated provirus sits quiescent in the host genome; the unusually long incubation period of slow-virus infections; and persistent tolerant infection, where the host mounts no immune response at all to a virus that remains readily demonstrable in tissue (the classical model being lymphocytic choriomeningitis virus in mice), with disease only appearing if that tolerance later breaks down.

Inclusion bodies are a visible legacy of some of these processes — aggregates of virions or viral protein that alter the staining properties of the infected cell enough to be diagnostic under the light microscope. They are classified by location: intracytoplasmic (acidophilic, pink on Giemsa/eosin — Negri bodies of rabies, Guarnieri bodies of vaccinia), intranuclear (basophilic — Cowdry type A, variable and granular, as in yellow fever and herpes simplex; Cowdry type B, small and circumscribed, as in poliovirus and adenovirus), or both together (the “owl’s eye” appearance of cytomegalovirus).

Laboratory Diagnosis

Viral diagnosis serves several distinct purposes at once — guiding antiviral therapy where one exists, screening blood donors, tracking disease burden for surveillance, investigating outbreaks, initiating post-exposure prophylaxis, and triggering specific clinical actions (pregnancy termination advice after first-trimester rubella, or immunoglobulin within 12 hours of birth for a hepatitis-B-exposed neonate).

Direct visualization covers electron microscopy (useful for viruses that are hard to culture, such as rotavirus, or for confirming growth in tissue culture, though expensive with limited sensitivity), immunoelectron microscopy (antibody-aggregated virus particles, improving on plain EM), fluorescent microscopy (specific antiviral antibody tagged with a fluorescent dye — useful for rabies antigen in skin biopsy, or for a syndromic respiratory-virus panel), and light microscopy of stained tissue sections to detect inclusion bodies.

Antigen detection uses formats such as ELISA and immunochromatographic tests to identify specific viral proteins directly in a specimen — HBsAg for hepatitis B, NS1 for dengue, nucleocapsid antigen for SARS-CoV-2, p24 for HIV. Antibody detection, similarly run by ELISA and related formats, distinguishes recent from past infection by pattern: IgM appearance or a fourfold rise in IgG titre signals recent infection, while stable IgG without a recent rise indicates past exposure or chronic infection.

Molecular methods have become central to modern viral diagnosis: PCR detects DNA directly; reverse transcriptase-PCR first converts RNA to DNA before amplification, extending the same principle to RNA viruses; multiplex PCR screens for several organisms causing one clinical syndrome in a single reaction; and real-time PCR, now the gold standard for many viral infections, adds the ability to quantify viral load — essential for monitoring treatment response in conditions like HIV and hepatitis B — while also being faster and more sensitive than conventional PCR.

Virus isolation by animal inoculation, embryonated egg inoculation, or tissue culture is labour-intensive and largely reserved now for research, vaccine production, or the rare diagnostic situation where nothing else will grow the organism. Tissue (cell line) culture is the only isolation method still in routine use, and cell lines themselves come in three tiers: primary cell lines (freshly taken from normal tissue, very limited division capacity, diploid), secondary/diploid cell lines (also normal and diploid, but capable of many more divisions before senescence — human fibroblast lines are the standard for recovering cytomegalovirus), and continuous cell lines (derived from cancer, effectively immortal, and therefore the most convenient to maintain — HeLa, HEp-2, Vero, and BHK are the everyday workhorses of diagnostic and vaccine virology). Viral growth in culture is most often detected by cytopathic effect — a virus-specific pattern of visible cell damage (syncytium formation for measles/RSV/HSV, rapid cell degeneration for enteroviruses, grape-like clumping for adenovirus) — though antigen detection, PCR, and electron microscopy can all confirm growth as well.

Treatment and Immunoprophylaxis

Because viruses depend entirely on host machinery, effective antiviral chemotherapy had to be designed carefully enough to hit only virus-specific targets — inhibiting viral DNA polymerase, neuraminidase, or specific viral proteases and polymerases — without disabling the host cell itself; even so, effective antivirals remain available for only a limited number of viral diseases (herpesviruses, influenza, and the hepatitis viruses being the best-covered groups).

Interferons (IFN-α, IFN-β) are part of innate immunity, produced quickly (within hours) by infected cells, and act indirectly — not by attacking the virus itself, but by inducing neighbouring host cells to make antiviral proteins that block viral protein synthesis. Because this response is non-specific and has no memory component, interferons differ fundamentally from antibody-mediated immunity, and their clinical use spans topical treatment (rhinovirus, genital warts, herpetic keratitis) to systemic treatment of chronic hepatitis B, C, and D, plus a secondary anti-proliferative use in certain cancers and autoimmune disease.

Vaccines exploit the fact that viral antigens are strongly immunogenic, and come in several forms, each with a different risk/benefit trade-off: killed (inactivated) vaccines are stable and safe even in immunodeficiency or pregnancy, but tend to cause more local reactogenicity and generally need multiple doses; live attenuated vaccines mimic natural infection closely enough to give strong, durable immunity from a single dose, but carry real risk in immunodeficient or pregnant recipients and are less stable to store; subunit vaccines, made by recombinant DNA technology to present only a specific viral antigen (hepatitis B surface antigen, HPV L1 protein), avoid the side effects of whole-virus preparations entirely.

Passive immunization with immunoglobulin provides immediate but temporary protection, useful specifically when a patient is immunodeficient or needs post-exposure cover before active immunity could possibly develop in time — since no memory response is generated, it protects only against the immediate exposure, never against future ones. Combined immunization (simultaneous vaccine plus immunoglobulin) is used where both immediate and durable protection are needed at once, most notably for hepatitis B (neonates of HBsAg-positive mothers) and rabies (severe class III exposures).

Hand-drawing notes only (no rendered diagrams)

Viral replication cycle (7 steps). Draw a single downward vertical sequence of seven labelled boxes connected by arrows: Attachment → Penetration → Uncoating → Biosynthesis → Assembly → Maturation → Release. Beside “Penetration,” branch three small labelled routes (phagocytosis/viropexis, membrane fusion, nucleic-acid-only injection) rather than drawing them as separate main-line boxes, since only one route applies per virus type. Label the eclipse phase as a bracket spanning from “Penetration” down to the point just before “Release,” not as its own box, since it describes a time interval rather than a step.

Retrovirus replication (HIV). A separate short linear sequence, since this differs enough from the general cycle to deserve its own sketch: (+)ssRNA → [reverse transcriptase, RNA-dependent DNA polymerase activity] → DNA:RNA hybrid → [reverse transcriptase, ribonuclease activity] → ssDNA → [DNA polymerase activity, same enzyme] → dsDNA → [transported to nucleus, integrase] → integrated into host chromosome → mRNA + genomic RNA. Label each arrow with the enzyme/activity responsible, since exam questions on this topic usually ask which specific activity of reverse transcriptase performs which step.

Positive-sense vs negative-sense ssRNA replication. Two short parallel sequences side by side. Positive-sense: (+)RNA → directly translated → early proteins (incl. RNA polymerase) → (−)RNA intermediate → back to (+)RNA → late proteins. Negative-sense: (−)RNA → [viral RNA polymerase, since it cannot be translated directly] → (+)RNA → serves both as mRNA (translation) and as template for more (−)RNA. Labelling which strand can and cannot be translated directly is the single fact most often tested here.

Not rendered

Symmetry types (icosahedral/helical/complex), inclusion-body classification, and cell-line types are already captured clearly as short lists/tables in notes.md and lnr.md — none of these is a multi-step mechanism that a rendered diagram would clarify beyond what the text already states.

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