Alternative splicing of HIV-1. (A) Organization of the HIV-1 genome. Filled boxes indicate open reading frames present in all isolates, light grey boxes indicate the Tev orf which is isolate specific. The long terminal repeats (LTR) are present at both ends of the proviral DNA. (B) Localization of splice sites, splicing regulatory elements and the Rev responsive element (RRE). 5' splice sites: D1a-5; 3' splice sites: A1-7. Splice sites A6/D5 are isolate specific and not functional in the isolate NL4/3 used in this study. Splice sites A1a/D1a defining exon 1a have been recently described . The nomenclature of the 3'ss is according to Stoltzfus [17,18] and Purcell and Martin  (in brackets). Splicing regulatory elements: M1, M2 (this report); ESSV [16,64]; ESS2p ; ESE2/ESS2 [17,32,43,44,49]; GAR [23,28]; ESS/ESE [19,20]; ISS ; ESE3 [17,21,24,25,33,65]; ESS3a, b [17,21,24,33,66]. (C) Splicing pattern and proteins encoded by the different mRNA classes. The 1.8 and 4 kb mRNAs contain obligatory sequences (dark grey) as well as alternative sequences (light grey) due to alternative usage of the splice sites. The nuclear export of the 4 kb mRNAs and the genomic full-length 9 kb mRNA is dependent on Rev binding.