AEGiS-12IAC: Infectious molecular clones with the non-homologous dimer initiation sequence found in different subtypes of HIV-1 can recombine and initiate a spreading infection.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

Infectious molecular clones with the non-homologous dimer initiation sequence found in different subtypes of HIV-1 can recombine and initiate a spreading infection.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:14 (abstract no. 11161)

St Louis D, Gotte D, Sanders-Buell E, Salminen MO, Carr JK, McCutchan FE
Henry M. Jackson Foundation, Rockville, MD, USA.

BACKGROUND: The direct involvement of recombination in the generation of HIV-1 diversity has emerged from analysis of viruses from multiple geographic locales. The formation of RNA dimers within the virion is essential for the high level of recombination exhibited by Retroviruses. Sequences responsible for in vitro HIV-1 RNA dimerization, dimerization initiation site, DIS, vary among HIV-1 subtypes and may be an obstacle for recombination.

METHOD: DIS loop sequences was determined in 75 viral isolates of subtypes A, B, C, D, E, F, G, and group O. We constructed deletion mutants of an infectious molecular clone of HIV-1, NL4-3, containing DIS variants identified in the HIV-1 subtypes and an artificial, AAAAAA DIS sequence and evaluated the effect of DIS variants on virus replication and recombination.

RESULTS: Two forms of the DIS occur among HIV-1 isolates examined to date: DIS (CG) in HIV-1 subtypes B and D and DIS (TA) in other subtypes and in group O. Unexpectedly, a naturally occurring but apparently rare DIS that is not palindromic and should form a less stable duplex, and an artificial, AAAAAA sequence that should be unable to form a duplex, both supported virus replication in vitro when introduced into the infectious molecular clone NL4-3. Furthermore, the recombination frequency between deletion mutants of NL4-3 was not significantly affected by DIS loop inhomology.

CONCLUSION: The different DIS found in HIV-1 subtypes B and D is not a primary impediment to RNA dimer formation, and recombination, with other subtypes and that A/D and B/F recombinants, already identified in the global epidemic may be an example of recombination between virus with different DIS.

Keywords: AEGIS, HIV-1, Virus Replication, Virion, Recombination, Genetic, Variation (Genetics), Dimerization, In Vitro, diagnosis, virology, genetics, ICA12
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