Biology Reference
In-Depth Information
newly produced virus particles. Recent progress in X-ray crystallogra-
phy, NMR spectroscopy and electron microscopy has provided a
wealth of structural data about how RNA and viral coat or capsid pro-
teins recognize each other with high specificity and affinity to result
in a highly accurate and efficient packaging process despite the
“chemical chaos” found inside of the host cell. Here we present an
overview of the atomic-level interactions between protein and RNA
that drive this process in three different systems: the MS2 bacterio-
phage, the alfalfa mosaic virus, and retroviruses.
Packaging of Viral RNA
The process of incorporating the newly produced viral genome into
the assembling particle is called packaging. This crucial step during
the viral lifecycle follows one of two general mechanisms termed con-
certed and sequential assembly. During concerted assembly the build-
ing blocks of the viral protein shell can only assemble in a productive
manner in the presence of the genomic nucleic acid. On the other
hand, the genomic nucleic acid is inserted into a preformed protein
shell in the course of the sequential assembly pathway.
During the packaging process, viral genomic RNA must be dis-
tinguished from cellular nucleic acids present in the same cellular
compartment in which the assembly occurs. This includes cellular
messenger RNAs, transfer RNA, ribosomal RNAs, and the degrada-
tion products thereof. In order to achieve this, the building blocks of
the viral protein shell must be able to recognize their correct part-
ner(s) in amid many similar nucleic acid molecules. For example, in
the case of many retroviruses, the genomic RNA exists only in
amounts of less than 1% of the total cellular RNA found in the cyto-
plasm. Nevertheless, the vast majority of newly produced virus parti-
cles contain the correct RNA. This remarkable degree of specificity
is accomplished by molecular-level interactions between distinct
sequences and structures within the coat or capsid proteins and the
genomic RNA. The unique sequences or structures found in the viral
genome are termed packaging signals. The size, secondary struc-
tures, and sequences found in RNA viruses range from simple hairpin
