INFECTIOUS MOLECULAR CLONES WITH THE NONHOMOLOGOUS DIMER INITIATION SEQUENCES FOUND IN DIFFERENT SUBTYPES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 CAN RECOMBINE AND INITIATE A SPREADING INFECTION IN-VITRO

Recombinant forms of human immunodeficiency virus type 1 (HIV-1) have been shown to be of major importance in the global AIDS pandemic. Vira l RNA dimer formation mediated by the dimerization initiation sequence (DIS) is believed to be essential for viral genomic RNA packaging and therefore for RNA recombination. Here, we demonstrate that HIV-1 reco mbination and replication are not restricted by variant DIS loop seque nces. Three DIS loop forms found among HIV-1 isolates, DIS (CG), DIS ( TA), and DIS (TG), when introduced into deletion mutants of HIV-1 reco mbined efficiently, and the progeny virions replicated with comparable kinetics. A fourth DIS loop form, containing an artificial AAAAAA seq uence disrupting the putative DIS loop-loop interactions [DIS (A6)], s upported efficient recombination with DIS loop variants; however, DIS (A6) progeny virions exhibited a modest replication disadvantage in mi xed cultures. Our studies indicate that the nonhomologous DIS sequence s found in different HIV-1 subtypes are not a primary obstacle to inte rsubtype recombination.