Virion Structure and Composition — Questions

Positive-sense RNA has the same sequence as mRNA and is translated directly (picornaviruses, flaviviruses, coronaviruses). Negative-sense RNA must first be transcribed by the virion’s own RNA-dependent RNA polymerase (RdRp).

Retroviruses replicate through a DNA intermediate using reverse transcriptase (an RNA-dependent DNA polymerase) rather than an RdRp. The hepadnaviruses (hepatitis B) use the same enzyme, though they are DNA viruses.

Priming cleavage does not switch fusion on; it leaves the fusion protein metastable (“primed but waiting”). The trigger (low endosomal pH for influenza, or receptor binding for others) then releases it into its fusion-active form.

The hepadnavirus (HBV) genome is a partially double-stranded circle repaired to cccDNA in the nucleus; this persistent template is a major reason HBV is so hard to cure.

Lipid solvents and detergents dissolve the envelope and destroy the infectivity of enveloped viruses while leaving naked viruses intact. This is the basis of the ether-sensitivity test for an envelope.

Only icosahedral and helical symmetry occur. Particles that are neither (poxviruses, the HIV-1 cone, tailed bacteriophages) are termed “complex”.

Retroviruses are uniquely diploid, packaging two copies of their positive-sense ssRNA genome; every other viral genome is haploid.

Rabies virus (a rhabdovirus) has a helical, enveloped nucleocapsid; the others are icosahedral. In vertebrate viruses, helical nucleocapsids are always enclosed within an envelope.

The envelope is taken from a host membrane during budding, so its lipids are host-derived and vary with the budding site, while the glycoprotein spikes embedded in it are virus-coded.

Any four of: Herpesviridae, Poxviridae, Hepadnaviridae, Retroviridae, Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, Coronaviridae, Togaviridae, Flaviviridae, Rhabdoviridae, Filoviridae, and the Bunyavirales families (including Arenaviridae).

The envelope is a host-derived lipid bilayer acquired at budding, which is why these viruses are labile to detergents, solvents and drying and generally do not survive the gastrointestinal tract.

Any four of: Adenoviridae, Papillomaviridae, Polyomaviridae, Parvoviridae, Picornaviridae, Caliciviridae, Astroviridae, Hepeviridae, Reoviridae (and Anelloviridae).

Naked capsids are environmentally stable and resistant to gastric acid and bile, so many non-enveloped families are transmitted by the faecal-oral route and resist common disinfectants.

Any four of: Paramyxoviridae, Orthomyxoviridae, Rhabdoviridae, Filoviridae, Coronaviridae, Pneumoviridae, and the Bunyavirales families (including Arenaviridae).

The protein subunits coil around the nucleic acid as a rod or filament. Among human viruses a helical nucleocapsid is essentially always wrapped in an envelope, so these are all enveloped RNA viruses.

Any four of: Adenoviridae, Herpesviridae, Papillomaviridae, Polyomaviridae, Parvoviridae, Picornaviridae, Caliciviridae, Astroviridae, Hepeviridae, Reoviridae, Togaviridae, Flaviviridae, Hepadnaviridae.

The icosahedron, a 20-faced shell built from repeated protein subunits, is the commonest capsid geometry. Several enveloped families (herpesviruses, togaviruses, flaviviruses, hepadnaviruses) carry an icosahedral capsid or core beneath the envelope, so symmetry and envelope status are independent descriptors.

The Baltimore system sorts viruses by genome type and the route each takes to messenger RNA.

• Group II (single-stranded DNA), one family: Parvoviridae (or Anelloviridae).
• Group III (double-stranded RNA), one family: Reoviridae.
• Group IV (positive-sense single-stranded RNA), three families: any three of Picornaviridae, Flaviviridae, Togaviridae, Coronaviridae, Caliciviridae, Hepeviridae, Astroviridae.
• Group V (negative-sense single-stranded RNA), three families: any three of Orthomyxoviridae, Paramyxoviridae, Rhabdoviridae, Filoviridae, Pneumoviridae, and the Bunyavirales families.

Retroviridae (group VI) and Hepadnaviridae (group VII) are the reverse-transcribing classes and fall outside groups II to V.

The dsRNA viruses (Reoviridae, Birnaviridae, Picobirnaviridae) all carry segmented genomes; rotavirus, a reovirus, has 11 segments.

The receptor is the host-cell molecule; the ligand is the viral molecule that binds it. For example, the SARS-CoV-2 spike is the ligand and ACE2 the receptor.

Vertex capsomeres bonded to five neighbours are pentons (pentamers); those on faces and edges, bonded to six, are hexons. An icosahedron has twelve vertices, hence twelve pentons.

The mature HIV-1 capsid is a fullerene cone: a lattice of CA hexamers closed by exactly twelve pentamers, curved into a cone. Neither icosahedral nor helical, so “complex”.

Nucleocapsid = the capsid plus the nucleic acid it encloses. Where present, an envelope is added around it to form the complete virion.

The non-glycosylated matrix protein (for example influenza M1) lines the inner face of the envelope, conferring rigidity and bridging the envelope and the nucleocapsid.

Naked enteric viruses (rotavirus, enteroviruses) resist stomach acid, fitting their faecal-oral spread, whereas enveloped viruses are inactivated at pH 5–6. Enveloped viruses are also the more heat-labile, −70 °C preserves infectivity for years, and prions resist boiling.

Cryo-EM now routinely achieves near-atomic resolution and has become the dominant technique for virus particles and their protein machines; X-ray crystallography is reserved for small viral enzymes and antibody-fragment complexes.

Symmetry strictly describes the capsid or nucleocapsid; the envelope is not a rigid symmetric shell, so the whole particle varies in size and shape, even though the nucleocapsid inside is ordered.

Sixty is the maximum in strictly identical environments. Caspar and Klug showed that subunits in quasi-equivalent positions allow multiples of 60 (the triangulation number, T), building larger shells from a single protein.

The light microscope resolves to about 300 nm; most viruses are smaller and so were invisible until electron microscopy. Poxviruses, the largest vertebrate viruses, sit right at that limit.