Three novel genes of human T-lymphotropic virus type III: immune reactivity of their products with sera from acquired immune deficiency syndrome patients.

Human T-lymphotropic virus type III or lymphoadenopathy associated virus (HTLV-III/LAV) is the cause of acquired immune deficiency syndrome (AIDS). In addition to the conventional retroviral genes involved in virus replication, namely, gag, pol, and env genes, DNA sequence analysis of HTLV-III genome predicted two additional open reading frames termed by us short open reading frame (sor) and 3' open reading frame (3' orf). Furthermore, functional analysis revealed another gene with transactivating function, termed tat. We have now structurally identified and functionally characterized these HTLV-III specific genes by way of cDNA cloning. DNA sequence analysis of the clones shows that the tat and 3' orf genes contain three exons and their transcription into functional mRNA involves two splicing events and that the sor gene contains at least two exons. In vitro transcription and translation of the cloned spliced sequences show that the sor, tat, and 3' orf genes code for polypeptides with apparent mobility of 24-25 kDa, 14-15 kDa, and 26-28 kDa, respectively. All three polypeptides are immune reactive and are immunogenic in the natural host. The results demonstrate that the three extra open reading frames of HTLV-III, two of which are unique to HTLV-III, are in fact genes that function in vivo and further allow the identification of three new and previously unrecognized HTLV-III antigens with differential immunogenicity in individuals with acquired immune deficiency syndrome and related disorders.