HIV-1 RNA dimerisation.
thesisposted on 2015-11-19, 09:10 authored by Malcolm. Haddrick
Genomic RNA isolated from retroviral particles is a dimer composed of two identical strands. A region called the dimer linkage site close to the 5' end of the RNA may be involved in forming the dimer. Several models for the formation of the HIV-1 genomic RNA dimer have been proposed. In the "kissing loop" model, dimerisation results from base pairing between homologous sequences in an RNA stem loop. In the guanine tetrad model interstrand guanine contacts form the dimer. Mutations have been made preventing the dimerisation of subgenomic RNAs in vitro by these mechanisms. To prevent the "kissing loop" dimer forming the complementary loop sequence 711GCGCGC716 was changed to 711AAACGC716. To prevent the guanine tetrad dimer forming residue G819 was changed to U. These mutations were introduced into a clone of HIV-lNL4-3 separately and collectively. All three clones produced infectious virions. Dimeric RNA with similar thermal stabilities was isolated from viruses containing either the single or the double mutations. The results suggest that sequences involved in forming a guanine tetrad are not important for HIV-1 RNA dimerisation. In contrast sequences involved in forming a kissing loop complex are not absolutely required, but are important in forming a stable HIV-1 RNA dimer.
Date of award1996-01-01
Awarding institutionUniversity of Leicester