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Journal of Virology, August 2009, p. 8099-8107, Vol. 83, No. 16
0022-538X/09/$08.00+0 doi:10.1128/JVI.00488-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Annealing to Viral RNA in Human Immunodeficiency Virus Type 1
Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital,1 Departments of Medicine,2 Microbiology and Immunology, McGill University, Montreal, H3T 1E2 Quebec, Canada,3 State Key Laboratory for Molecular Virology and Genetic Engineering, Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China4
Received 9 March 2009/ Accepted 26 May 2009
In protease-negative human immunodeficiency virus type 1 (HIV-1) [Pr(-)], the amount of
annealed by Gag is modestly reduced (
25%) compared to that annealed by mature nucleocapsid (NCp7) in protease-positive HIV-1 [Pr(+)]. However, the
annealed by Gag also has a strongly reduced ability to initiate reverse transcription and binds less tightly to viral RNA. Both in vivo and in vitro, APOBEC3G (A3G) inhibits
annealing facilitated by NCp7 but not annealing facilitated by Gag. While transient exposure of Pr(-) viral RNA to NCp7 in vitro returns the quality and quantity of
annealing to Pr(+) levels, the presence of A3G both prevents this rescue and creates a further reduction in
annealing. Since A3G inhibition of NCp7-facilitated
annealing in vitro requires the presence of A3G during the annealing process, these results suggest that in Pr(+) viruses NCp7 can displace Gag-annealed
and re-anneal it to viral RNA, the re-annealing step being subject to A3G inhibition. This supports the possibility that the initial annealing of
in wild-type, Pr(+) virus may be by Gag and not by NCp7, perhaps offering the advantage of Gag's preference for binding to RNA stem-loops in the 5' region of viral RNA near the
annealing region.
Published ahead of print on 3 June 2009.
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