Question

How is the viral nucleic acid packaged into a virus particle and distinguished from other nucleic acids in the cell? Explain for segmented and non-segmented viral genomes.

Answer 1

There are two main strategies for viral genome packaging. Many viruses assemble their capsids around the viral genomes, such as the ssRNA helical tobacco mosaic virus, the ssRNA icosahedral bacteriophage R17 the ssRNA conical HIV and the dsRNA unsegmented icosahedral Totiviridae viruses (e.g. L-A virus of yeast). Similarly small dsDNA viruses, with a less than 20 kb genome, assemble the shell around condensed DNA. On the other hand, some dsDNA viruses (e.g. tailed bacteriophages and herpesviruses) and dsRNA viruses (e.g. φ6 and φ12 bacteriophages) form protein capsid shells first and then package their genomes into the procapsids. For the latter viruses, a motor is required to perform the packing with energy supplied by hydrolysis of ATP.

Viral genome packaging must differentiate between host and viral nucleic acid. A strategy employed by many viruses is that the viral capsid protein contains a binding site which recognizes a specific sequence of the viral genome. For example, in unsegmented Totiviridae dsRNA viruses, such as the L-A virus of yeast, there is a secondary structure (stem-loop) and a specific sequence at the 5' end of the genome that are recognized by the polymerase-group antigen (pol-gag) fusion protein. However, segmented dsRNA viruses such as Reoviridae etc, has complementarity between regions of the segments which helps the virus to include one of each of the genomic RNA molecules. Alternatively, for the segmented dsRNA bacteriophage φ6, the procapsid may have specific binding sites for each of the different segments.

Double-stranded DNA viruses have evolved yet other strategies for packaging their own genome. Most bacteriophages and herpesviruses replicate their genomes as head-to-tail concatemers. A “terminase” complex of two proteins, which is also a part of the packaging motor, recognizes a specific sequence or structure on the concatemeric DNA and makes the initial cut to generate the free end at which packaging is initiated. After one or slightly more than one genome length of DNA has been packaged into the head, the same nuclease makes another cut to terminate packaging. These proteins that are required for the generation of genome termini were named “terminases”. Certain dsDNA viruses such as bacteriophage φ29 and adenoviruses employ protein-primed DNA replication and do not produce concatemers. These viruses recognize their own DNAs through the terminal primer proteins that are covalently linked to the genome ends.