Introduction to viral genomes

Size and structure of viral genomes

The size of viral genomes varies nearly a thousandfold from the smallest to the largest. There are DNA viruses along the entire gradient, starting with the small circovirus, whose 1.75 Kilobases single-stranded genome is dwarfed by Megavirus’ 1.25 megabase-pair double-stranded genome (Figure 1).

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Figure 1 – Comparative genomics. A size comparison of viral genomes and major groups of living organisms. Source Pearson Education

Single-stranded or double-stranded RNA genomes are often smaller than DNA virus genomes. Prokaryotic (organisms lacking a nucleus) genomes are typically much larger than viral genomes, and eukaryotic (organisms with a nucleus) genomes are significantly larger than prokaryotic genomes (Figure 1).

Regardless of the size of the viral genome, transcription (reading of the code and generation of RNA from it) of the genes must take place and new copies of the genome must be made once the virus has infected the host. Viral assembly can be initiated only after viral proteins are synthesised as a result of the translation (conversion of the generated RNA code into a sequence of amino acids) of viral transcripts. For some RNA viruses, the genome also serves as the mRNA. However, for most viruses, viral mRNA must first be produced from the DNA or RNA genome via transcription.

The Baltimore Scheme for Viral Classification

David Baltimore, a virologist who shared the Nobel Prize in Physiology or Medicine in 1975 with Howard Temin and Renato Dulbecco for discovering retroviruses and reverse transcriptase, established a virus classification scheme. This system distinguishes seven kinds of viruses based on the connection of the viral genome to its mRNA (Figure 2). By convention, viral mRNA is always considered to be of the positive-strand (+) configuration. To comprehend the biology of a given virus class, one must first understand the nature of the viral genome and the mechanisms necessary to produce complementarity mRNA (Figure 2).

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Figure 2 – The Baltimore classification of viral genomes. Seven classes of the viral genome are known (I-VII). The genomes can be either DNA (a) or RNA (b), and either single-stranded (ss) or double-stranded (ds). Source Pearson Education

The Baltimore class I includes viruses with double-stranded DNA. Class I viruses, like the common bacteriophage T4, produce mRNA and replicate their genomes using the same method as the host cell. Positive-strand viruses, also known as “positive-strand viruses,” or negative-strand viruses, sometimes known as “minus-strand viruses,” can both have single-stranded genomes.

The DNA genomes of class II viruses are single-stranded positive-strand. If such a genome were transcribed, it would result in a message that is negative-sense in nature. Therefore, a complementary DNA strand must first be created to form a double-stranded DNA intermediate, also known as the replicative form, before class II viruses can make mRNA. This intermediate serves as a source for additional genome copies and for transcription, with the positive strand becoming the genome and the negative strand being discarded (Figure 2). All single-stranded DNA viruses are positive-strand viruses, with only one known exception, the Anelloviridae.

DNA viruses and RNA viruses produce messenger RNA (mRNA) in different ways. Host RNA polymerases require a DNA template, and do not catalyse the synthesis of RNA from an RNA template. As a result, depending on the virus, RNA viruses must either carry or encode in their genomes an RNA-dependent RNA polymerase known as RNA replicase. In class IV viruses, which have a positive strand of RNA, the genome is also mRNA. However, for negative-strand RNA viruses (class V), RNA replicase must generate a positive strand of RNA from the negative-strand template, which is subsequently employed as mRNA. This mRNA serves as a template to create additional negative-strand genomes (Figure 2). Similar issues arise for class III RNA viruses, but they begin with double-stranded (+/-) RNA rather than just a positive or negative strand.

Retroviruses are animal viruses that replicate through a double-stranded DNA intermediary but have single-stranded RNA genomes with a positive-strand structure (class VI). The process of transcribing information from RNA into DNA is known as reverse transcription, and it is catalysed by an enzyme known as reverse transcriptase.

Finally, class VII viruses are extremely rare viruses with double-stranded DNA genomes that replicate via an RNA intermediary. This class of viruses also use reverse transcriptase.

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