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Published on: December 23, 2016
Evidence of recombination between 3' and 5' LTRs in macaques inoculated with SIV DNA
Stephen J Kent1, C Jane Dale, Scott Preiss
1Department of Microbiology and Immunology, University of Melbourne, Parkville, Vic, 3010, Australia. skent@unimelb.edu.au
Abstract:
Proviral SIV DNA inoculation of macaques is an efficient method to initiate wild-type and attenuated SIV infections. However, we found that macaques inoculated with SIV DNA engineered to contain a single 105-bp deletion in the 3' nef/LTR overlap region had SIV sequences subsequently isolated that had partially or fully repaired the deletion with wild-type sequence. Animals inoculated with SIV DNA containing identical deletions in both the 5' and 3' LTRs did not repair the deletion. Recombination events occurred early, most likely by homologous recombination with sequences from the wild-type 5' LTR. This sequence analysis is the first demonstration of homologous recombination in vivo following administration of a single SIV strain.
Insights
Researchers discovered that macaques inoculated with simian immunodeficiency virus (SIV) DNA could repair deletions in the viral genome. This in vivo homologous recombination occurred early, suggesting a novel mechanism for viral sequence evolution.
Area of Science:
- Virology
- Molecular Biology
- Primate Models
Background:
- Proviral simian immunodeficiency virus (SIV) DNA inoculation is a standard method for establishing SIV infections in macaques.
- Understanding viral genome dynamics during infection is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the in vivo repair mechanisms of engineered deletions in SIV DNA following inoculation in macaques.
- To determine if homologous recombination occurs and identify potential mechanisms.
Main Methods:
- Inoculation of macaques with SIV DNA containing specific deletions in the 3' nef/LTR overlap region.
- Isolation and sequence analysis of SIV DNA from inoculated animals over time.
- Comparison of sequences from animals inoculated with single versus dual LTR deletions.
Main Results:
- Macaques inoculated with SIV DNA having a single deletion in the 3' nef/LTR overlap region showed evidence of deletion repair with wild-type sequences.
- Animals receiving SIV DNA with identical deletions in both 5' and 3' LTRs did not exhibit deletion repair.
- Sequence analysis indicated early recombination events, likely through homologous recombination with the 5' LTR.
Conclusions:
- This study provides the first demonstration of homologous recombination in vivo after administration of a single SIV strain.
- Engineered deletions in SIV DNA can be repaired by homologous recombination in macaques, influencing viral sequence evolution.
- The findings highlight the plasticity of the SIV genome and potential implications for vaccine and antiviral strategies.
