Viral genomes and diversity

What is the Baltimore classification scheme?

A system that classifies viruses based on their genome type and the pathway used to generate mRNA for protein synthesis.

• It includes 7 classes (I–VII) depending on whether genomes are DNA or RNA, single- or double-stranded, and positive or negative sense.

What is a positive-sense (+) RNA genome?

An RNA genome with the same sense as viral mRNA, meaning it can be directly translated by host ribosomes.

What is a negative-sense (–) RNA genome?

An RNA genome complementary to viral mRNA; it must be copied by viral RNA-dependent RNA polymerase into a positive-sense strand before translation.

What is rolling-circle replication and where does it occur?

A replication mechanism in which a circular DNA/RNA template produces long concatameric strands(contains multiple copies of the same DNA sequence linked in series) that are later cleaved into unit genomes.

• Occurs in Class II ssDNA phages (e.g., M13, ΦX174)

• Class I viruses (herpesviruses, λ phage)

What are lytic, persistent, and latent infections?

• Lytic: Cell is destroyed upon virus release

• Persistent: Slow, continuous release without immediate cell death.

• Latent: Viral genome remains silent, may reactivate later (e.g., herpes).

How do Class I dsDNA viruses generate mRNA?

Use host (or viral) DNA-dependent RNA polymerase to transcribe mRNA from dsDNA. Their replication resembles that of host cells.

How do Class I viruses replicate their genomes and what is an exception?

Replication usually occurs in the nucleus using host DNA polymerases, except poxviruses, which replicate in the cytoplasm and encode their own polymerases.

Example replication mechanism of a Class I virus?

Herpesvirus uses rolling-circle replication after early/late gene expression phases.

What is special about adenovirus genome replication?

It is conservative, not semiconservative; the negative strand is synthesised first, then converted to dsDNA.

How do Class II ssDNA viruses generate mRNA?

The ssDNA is first converted into a dsDNA replicative form by host enzymes, which is then transcribed to mRNA

How do Class II viruses replicate genomes?

Through rolling-circle replication, producing concatamers later processed to single-stranded genomes.

e.g. Parvoviruses, filamentous M13, and ΦX174 bacteriophages

How do Class III dsRNA viruses generate mRNA?

Viral RNA-dependent RNA polymerase (RNA replicase) within the virion synthesizes positive-sense mRNAs from each dsRNA segment

How do Class III viruses replicate their genomes?

After producing ( + ) strands, these serve as templates to synthesize new ( – ) strands, forming new dsRNA segments

Example Class III virus?

Reoviruses such as rotavirus, with 10–12 dsRNA segments

How do Class IV viruses express their genes?

Their genomes act directly as mRNA, translated immediately upon entry into the host cell.

• These positive-sense ssRNA genomes can be directly translated by the host's ribosomes to produce viral proteins.

How do Class IV viruses replicate genomes?

The genome is translated to produce an RNA replicase, which synthesises a complementary ( – ) RNA strand that then serves as a template for new (+) genomes.

Example life cycle feature of poliovirus?

Produces a single polyprotein that is autoproteolytically cleaved into functional proteins.

• VPg on the 5′ end and poly-A tail on 3′ end are key features of its genomic structure.

How do coronaviruses express multiple proteins from a +RNA genome?

Through a nested set of monocistronic subgenomic mRNAs, each translated into specific proteins that are essential for viral replication and assembly.

How do Class V (- ssRNA) viruses express genes?

They must carry a viral RNA-dependent RNA polymerase in the virion to convert (–) RNA into ( + ) mRNAs

How do Class V viruses replicate genomes?

( + ) mRNAs also serve as templates for full-length ( + ) RNA, which is then copied back into ( – ) genomes and packaged into new virions for infection.

What is antigenic shift in influenza?

A major change in the virus's surface proteins due to the reassortment of genome segments when two different strains infect the same cell, leading to new subtypes that can evade immunity.

Key glycoproteins in influenza and their roles?

• Haemagglutinin (HA): mediates attachment; immunogenic

• Neuraminidase (NA): cleaves sialic acid, enabling viral release.

What is antigenic variation?

The ability of a pathogen to alter surface antigens to evade immune detection (e.g., influenza antigenic shift; trypanosomes)

What is reverse transcriptase?

A viral enzyme that synthesises DNA from an RNA template; used by Classes VI (retroviruses) and VII (Hepadnaviruses).

How do Class VI viruses (retroviruses) generate mRNA?

After reverse transcription of the RNA genome into dsDNA, the integrated provirus is transcribed by host RNAPol II to make viral mRNAs.

What is a key example of Class VI viruses and how is the genome replicated?

HIV (Human Immunodeficiency Virus)

• The RNA in the virion is positive strand.

• After infection, it is copied into DNA by reverse transcriptase.

• Eventually a dsDNA version of the viral genome is formed and this integrates into a host chromosome.

• Integration can occur anywhere in the genome but usually occurs within an area of active chromatin.

• The integrated copy remains latent as a provirus but it can be induced and transcribed by the cellular RNA Pol to make new viral genomes as well as mRNAs that are translated to make viral particle proteins

What proteins are produced from the gag–pol–env reading frame in HIV?

• A frameshift allows translation of Pol (RT, integrase).

• Late splicing produces Env glycoproteins and structural proteins (gag) that form the viral core.

How do Class VII viruses (dsDNA viruses requiring an RNA intermediate) generate mRNA?

• Their partially dsDNA genome becomes fully ds

• Host RNA polymerase II transcribes mRNAs and a pregenomic RNA

• Reverse transcriptase copies the pregenomic RNA into partially dsDNA within assembling virions.

Example of Class VII virus?

Hepatitis B virus (HBV), with 3–4 kb partially double-stranded DNA genome