Identification and visualization of the dimerization initiation site of the prototype lentivirus, maedi visna virus: a potential GACG tetraloop displays structural homology with the alpha- and gamma-retroviruses.
Dimerization of retroviral genomic RNA is essential for efficient viral replication and is mediated by structural interactions between identical RNA motifs in the viral leader region. We have visualized, by electron microscopy, RNA dimers formed from the leader region of the prototype lentivirus, maedi visna virus. Characterization by in vitro assays of the domains responsible for this interaction has identified a 20 nucleotide sequence that functions as the core dimerization initiation site. This region is predicted to form a GACG tetraloop and therefore differs significantly from the kissing loop palindromes utilized to initiate dimerization in primate lentiviruses. The motif is strongly conserved across the ovine and caprine lentiviruses, implying a critical functional role. Furthermore, the proposed GACG tetraloop exhibits marked structural homology with similar structural motifs present in the leader regions of the alpha- and gamma-retroviruses, and the maedi visna virus dimer linkage region is capable of forming heterodimeric species with the Moloney murine leukemia virus Psi domain. This may be indicative of commonality of origin of the two viruses or convergent evolution.
Monie
Tom P
TP
Department of Medicine, University of Cambridge, Level 5, Addenbrooke's Hospital, UK.
Greatorex
Jane S
JS
Maynard-Smith
Laura
L
Hook
Ben D C
BD
Bishop
Naomi
N
Beales
Lucy P
LP
Lever
Andrew M L
AM
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D019281:Dimerization; D006041:Goats; D016086:Lentivirus / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D012756:Sheep; D014158:Transcription, Genetic; D014779:Virus Replication; D014790:Visna-maedi virus / Q000235:genetics* / Q000502:physiology
D017931:DNA Primers; D012367:RNA, Viral