5.1 What a virus is #
5.1.1 Definition, size, and structure #
A virus has no metabolism of its own. The virion is a genome in a protein capsid, sometimes in a membrane, with no ribosomes and no fission. Replication is the host’s machinery redirected. Giant viruses encode pieces of translation and can be hundreds of nanometres across; they still need a cell. Typical virions are about 20 nm to a few hundred. Electron microscopy showed the shapes.
Structure Of T7 Phage
A helical capsid winds subunits along the nucleic acid, as in tobacco mosaic virus and the influenza nucleocapsid. An icosahedral capsid closes twenty triangular faces, as in adenoviruses and picornaviruses. T-even phages add a contractile tail and fibres to an icosahedral head. An envelope is host membrane, taken at exit and studded with viral glycoproteins. Naked enteric viruses often survive acid and drying. Enveloped viruses need the membrane intact, so detergents and drying inactivate them. That fact returns in Chapter 7. It is not a decontamination schedule.
5.1.2 Genomes, and why the classes are about mRNA #
Baltimore’s question (1971) is the useful one: what must happen before a host ribosome sees viral mRNA? Ribosomes translate only plus-sense RNA. A cell does not keep a viral polymerase ready, so some virions must bring one.
| Class | Genome | Route to mRNA | Polymerase in the particle? | Examples |
|---|---|---|---|---|
| I | dsDNA | ordinary transcription | usually no; poxviruses yes (they stay in the cytoplasm) | herpesviruses, T4 |
| II | ssDNA | become dsDNA, then transcribe | no | parvoviruses |
| III | dsRNA | transcribe one strand | yes | reoviruses |
| IV | +ssRNA | the genome is mRNA | no, until the cell translates one | picornaviruses, flaviviruses |
| V | −ssRNA | transcribe the genome | yes | influenza, rabies |
| VI | +ssRNA | reverse-transcribe, integrate, then host transcription | reverse transcriptase | HIV |
| VII | dsDNA | RNA intermediate, then DNA again | reverse transcriptase | hepatitis B |
Most DNA viruses use the nucleus. Poxviruses do not, and bring their own transcription system. Most RNA viruses stay in the cytoplasm. Influenza and retroviruses are the exceptions that enter the nucleus.
5.2 Bacteriophages #
5.2.1 One-step growth and the T-even lytic cycle #
Ellis and Delbrück (1939) infected cells together and stopped an immediate second round. Infectious particles are absent, then appear, then level off. During eclipse, broken cells still yield nothing infectious: the parent is uncoated and progeny are not yet assembled. The latent period ends only when the first particles are free outside. Burst size is the yield per cell, of the order of a hundred for a T-even phage in the classical conditions, and lower if the host is starved. The curve is assembly, not leakage of the inoculum.
Lysogenic And Lytic Cycle
T4 is virulent, never lysogenic. Tail fibres recognise LPS and OmpC. The tail injects DNA; the capsid stays outside, which is the geometry Hershey and Chase used. Early genes destroy host DNA, redirect host RNA polymerase, and replicate a genome in which hydroxymethylcytosine, glucosylated, replaces cytosine, so ordinary restriction misses it. Late genes build the particle. A holin opens the membrane and an endolysin cuts peptidoglycan. The burst is lysis, counted. Using T4 as a genetic system is genetics, not this cycle.
5.2.2 Lysogeny of lambda #
Lambda can lyse or integrate. A prophage is copied with the chromosome, and the lysogen is immune to another lambda of the same immunity type. Operator maps are not required. cI represses the lytic promoters and keeps itself on, so the prophage stays silent. Cro turns cI off and commits the cell to lysis. CII, while it lasts, turns cI on. High multiplicity makes more CII, so lysogeny wins when many phages already share the cell. In a fast-growing cell a host protease destroys CII and lysis wins.
Integration is site-specific, between the galactose and biotin operons, by integrase. Excision also needs excisionase. DNA damage activates RecA; cI then cleaves, as LexA does in the SOS response, and the lytic genes come on. The SOS regulon itself is molecular biology.
Imprecise excision can carry a neighbouring bacterial gene: specialised transduction. Generalised transduction packages a random host fragment instead. Genetics maps with both. Diphtheria toxin and cholera toxin ride on phages. Without the prophage there is no toxin.
5.3 Animal viruses #
5.3.1 Entry, uncoating, and exit #
Attachment to a receptor sets much of host and tissue range. Enveloped viruses fuse at the plasma membrane or, after endocytosis, when low pH springs the fusion protein. Naked viruses often breach an endosome. Uncoating frees the genome, and that interval is eclipse.
Envelope glycoproteins travel the secretory pathway and collect where the particle will bud. The route itself is cell biology. Naked viruses often accumulate until the cell lyses. Budding takes membrane with the particle. Neuraminidase exists so influenza does not stay stuck to the cell that made it.
5.3.2 Influenza #
Influenza A is enveloped, with eight negative-sense RNA segments, each already bound to a viral RNA polymerase because the genome cannot be translated. Haemagglutinin binds sialic acid and later fuses membranes. Neuraminidase cuts sialic acid and frees progeny. M2 is a proton channel. Endosomal acid triggers fusion and, through M2, helps ribonucleoproteins uncoat. They enter the nucleus. Transcription starts by cap-snatching: the polymerase steals capped oligonucleotides from host pre-mRNA, and two segments are spliced. Replication then makes full-length copies without caps. Glycoproteins reach the plasma membrane by the secretory pathway, segments are packaged as a set, and the particle buds. Neuraminidase stops clumps forming.
Drift is point mutation in the two glycoproteins. The RNA polymerase does not proofread, so antibody to last year’s surface fits this year’s less well. Shift is reassortment: two influenza A viruses in one cell can package a mixed set of segments, and a novel haemagglutinin can meet a population with no matching immunity. Shift needs segments plus an animal reservoir, which type A has, largely in birds. Type B drifts without that reservoir. Pandemic history is this kind of event. No death tolls and no values of R0 are assigned. Adamantanes block M2; resistance has retired them clinically. Neuraminidase inhibitors block release. Another class blocks the cap-snatching endonuclease. Targets only: no structures and no doses.
5.3.3 HIV #
HIV is an enveloped retrovirus, class VI, with two copies of plus-sense RNA. gp120 binds CD4 and then CCR5 or CXCR4; gp41 fuses at the plasma membrane. People without functional CCR5 resist strains that need it. Reverse transcriptase copies RNA to DNA, RNase H removes the RNA, and the second strand is made, without proofreading, so one person carries a swarm of genomes and a single drug fails. Integrase inserts the DNA even into a non-dividing cell. The provirus is permanent. Host RNA polymerase II transcribes it; Tat boosts that transcription and Rev exports unspliced RNA, both message and genome. The bud is immature until protease cuts Gag and Gag–Pol and the capsid condenses.
The drug classes are nucleoside and non-nucleoside reverse-transcriptase inhibitors, integrase inhibitors, protease inhibitors, fusion inhibitors, and CCR5 blockers. A silent provirus in a resting memory CD4 T cell is not a substrate for drugs that act only while the virus is replicating. Loss of those T cells, and the opportunists that follow, are the clinical consequence. The immunology is not taught here.
5.4 Prions and viroids #
5.4.1 Protein-only and RNA-only agents #
PrPC is a normal neuronal surface glycoprotein, largely helical. PrPSc has the same sequence, a beta-rich fold, and the ability to template further conversion. It resists protease that destroys PrPC. Prusiner’s argument for scrapie was that infectivity did not track with nucleic acid and survived treatments, including ultraviolet irradiation, that kill viruses. An animal with no PrPC cannot propagate a prion. The diseases are scrapie, BSE, chronic wasting disease, kuru, Creutzfeldt–Jakob disease, and variant CJD linked to BSE exposure. Incubation is long; the brain becomes spongy; there is no immune response, because the protein is self. Cases are sporadic, inherited, or acquired. How prions are prepared is not described.
Viroids are circular single-stranded plant RNAs of a few hundred nucleotides, with no capsid and no gene for a protein. Potato spindle tuber viroid is the type. Host RNA polymerase copies them; in one family the RNA is a self-cleaving ribozyme. They are not hepatitis D, which borrows the hepatitis B envelope.
| Agent | Nucleic acid | Protein it encodes | Capsid | Hosts |
|---|---|---|---|---|
| Virus | DNA or RNA | yes | yes | cells of one or another domain |
| Viroid | small circular RNA | no | no | plants |
| Prion | none | none; host PrP refolds | no | animals |
5.5 Key terms, summary, and self-check #
Key terms. Virion; capsid; envelope; Baltimore class; eclipse; latent period; burst size; cI; Cro; prophage; haemagglutinin; neuraminidase; drift; shift; reverse transcriptase; integrase; protease; PrPSc; viroid.
Summary. A virus is a genome in a capsid, sometimes enveloped, and must make mRNA. That route is the Baltimore class, and it decides whether a polymerase is inside the particle. Eclipse is uncoating without infectious progeny; the latent period ends at release. T4 injects, takes over, and lyses. Lambda’s cI keeps a prophage; Cro chooses lysis; a phage can thereby carry a toxin gene. Influenza’s eight negative-sense segments explain nuclear cap-snatching, drift, and shift. HIV’s reverse transcriptase, integrase, and protease are the drug targets, and integration is why infection persists. Prions propagate a fold. Viroids are naked circular plant RNA.
Self-check.
1. A particle contains RNA that is not itself mRNA, plus an RNA-dependent RNA polymerase. Which Baltimore class, and why is the enzyme inside?
2. What appears at the end of eclipse, and what event ends the latent period?
3. What do cI and Cro each commit lambda to, and why does high multiplicity favour one?
4. Why can influenza A shift, while a non-segmented RNA virus can only drift? Name the two surface proteins.
5. Name the three HIV enzymes used as drug targets. What does a prion lack that every virus has?
