Lever, Andrew ML

Retrovirology

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Andrew ML Lever

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RNA packaging in lentiviruses

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Retrovirology
Open AccessInvited speaker presentation
RNA packaging in lentiviruses
Andrew ML Lever
Address: Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ , UK
The selection by a lentivirus of its genomic RNA from the
background of a vast excess of cellular messenger RNAs
and sub-genomic viral RNAs occurs with high specificity.
The nature and site of the specific interaction between the
unspliced RNA genome and the gag polyprotein, which is
responsible for its capture, is still poorly understood and
the routes by which the two partners arrive at the initial
site of interaction and what happens thereafter are simi-
larly obscure. We have been studying this process in a
number of different lentiviruses including HIV-1, HIV-2,
SIV and FIV. A number of common themes emerge. Spe-
cificity of the interaction depends on RNA motifs, com-
monly short runs of purines in the context of specific
structures. The cis-acting packaging signal structures are at
the 5' end of the genome but may be upstream or down-
stream of the major splice donor, hence they may require
additional mechanisms for specificity in some cases. The
5' structured untranslated region, together with sequences
stretching into the gag open reading frame appear to be
able to form more than one structure commonly involv-
ing long-range interactions and the different structures
may contribute to the different functions of spliced and
unspliced RNA. Different structures also very likely form
at different stages of the passage of the genomic RNA from
transcription through to encapsidation, reflecting interac-
tions with different cellular chaperone proteins as well as
trans acting viral proteins involved in trafficking of the
RNA through the cell. There is good evidence for signifi-
cant structural change occurring when the RNA interacts
with protein ligands such as the Gag and the degree of
conformational change may be quite profound. There is a
close link between RNA dimerisation and packaging and
it seems likely that the RNA is initially packaged as a
dimer, however, whether RNA dimerisation is a necessary
step for packaging is less clear and evidence from some
viral systems, including HIV-2, suggests that the link with
packaging is more critical to ensure a dimeric genome is
present for maximum infectivity of the virus when it
enters the next host cell. Newer structural analytical tech-
niques are teaching us more about the nature of the RNA
genome and its structural changes during the packaging
process.
from Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts
Montpellier, France. 21-23 September 2009
Published: 24 September 2009
Retrovirology 2009, 6(Suppl 2):I13 doi:10.1186/1742-4690-6-S2-I13
<supplement> <title> <p>Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts</p> </title> <note>Meeting abstracts - A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S2-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-6-S2-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S2/I13
© 2009 Lever; licensee BioMed Central Ltd. 


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RNA packaging in lentiviruses

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