Variant Effects of Non-Native Kissing-Loop Hairpin Palindromes on HIV Replication and HIV RNA Dimerization: Role of Stem−Loop B in HIV Replication and HIV RNA Dimerization†

The genome of all retroviruses consists of two identical RNAs noncovalently linked near their 5‘ end. In vitro synthesized RNAs from human immunodeficiency virus type 1 (HIV-1) can form loose or tight dimers depending on whether their respective kissing-loop hairpins (nts 248−270 in HIV-1Lai) bond via their hexameric autocomplementary sequences (ACS), also called palindromes, or via the ACS and stem sequences [Laughrea, M., and Jette, L. (1996) Biochemistry 35, 1589−1598]. To understand the role of the ACS in HIV-1 replication and in the formation and stability of HIV-1 RNA dimers, we replaced the central CGCG261(or tetramer) of the HIV-1Lai ACS by two other HIV-1 tetramers (UGCA/UGCG), four non-HIV-1 tetramers [GUAC, UUAA (respectively found in HIV-2Rod and SIVmnd), GGCC and AGCU (absent from HIV and SIV viruses)], or GGCG, a nonpalindromic tetramer. The infectivity of GGCC, GUAC, and UGCA viruses was unchanged or insignificantly decreased; the infectivity of AGCU and UGCG viruses was decreased by 80%; t...