The complete nucleotide sequence of two human T-cell leukaemia type III (HTLV-III) proviral DNAs each have four long open reading frames, the first two corresponding to the gag and pol genes. The fourth open reading frame encodes two functional polypeptides, a large precursor of the major envelope glycoprotein and a smaller protein derived from the 3'-terminus long open reading frame analogous to the long open reading frame (lor) product of HTLV-I and -II.

SummaryTo determine the extent and nature of genetic variation present in independent isolates of HTLV-IIIILAV, the nucleotlde sequences of the entire envelope gene and parts of gag and pal were determined for two AIDS viruses. The results indicated that variation throughout the viral genome is extensive and that the envelope gene in particular is most highly variable. Within the envelope, changes were most prevalent within the extracellular region where clustered nucleotlde substitutions and deletlonslinsertlons were evident. Based on predicted secondary protein structure and hydrophillcity, these hypervariable reglons represent potential antigenic sites. In contrast to the hypervariable regions, other sequences in the extracellular envelope and the overall envelope structurrc (lncludlkg 18 of 18 cysteine residues), as well as most of the transmembrane region, were highly conserved.

The nucleotide sequence of the long terminal repeat sequence (LTR) of the human T-cell leukemia (lymphotropic) virus type III (HTLV-III) was determined. This virus is associated etiologically with the acquired immune deficiency syndrome. The LTR was found to be 634 base pairs in length with U3, R, and U5 regions of 453, 98, and 83 bp, respectively. The proviral DNA is flanked by a 7-base-pair direct repeat. The promoter and polyadenylation signals are situated 27 and 24 base pairs upstream from the respective transcriptional initiation and polyadenylation sites. The primer binding site is complementary to transfer RNA-lysine. The LTR of HTLV-III, like that of HTLV-I, showed a limited homology to enhancer-like sequences within two genes expressed specifically in T lymphocytes, T-cell growth factor, and gamma-interferon. Structural comparisons revealed that the LTR of HTLV-III is distantly related to those of HTLV-I, HTLV-II, and bovine leukemia virus.

The isolation from macaques of retroviruses related to human immunodeficiency virus (HIV) led to the identification of a second group of human retroviruses (termed HIV-2), which are prevalent in West Africa and closely related to the simian immunodeficiency virus (SIV). We have cloned and determined the complete nucleotide sequence of the human West African retrovirus HIV-2NIH-Z and compared it to that of a previously described strain of HIV-2 (HIV-2ROD) as well as to SIV and HIV-1. We have reached the following conclusions: (i) The HIV-2 isolates are (slightly) more closely related to each other than to SIV, compatible with their isolation from different species. (ii) The variability between HIV-2 isolates is similar in degree and kind to that found among HIV-1 isolates. The equivalent degrees of intragroup divergence suggest that HIV-1 and HIV-2 have existed in their present ranges in Africa for approximately equal lengths of time. The fact that acquired immunodeficiency syndrome is widespread in regions where HIV-1 is prevalent but not in regions where HIV-2 is prevalent suggests a substantial difference in the morbidity rates associated with HIV-1 vs. HIV-2 infection. (iii) HIV-2 and SIV are related to each other more closely than they are to HIV-1.

The genome of the virus associated with the acquired immune deficiency syndrome (AIDS), human T-lymphotropic virus type III (HTLV-III), includes two open reading frames, not found in other retroviruses. One of these, designated 3' open reading frame (3'orf) is 648 base pairs (bp) in length, and overlaps with the 3' long terminal repeat (LTR) sequences. Sequences of additional HTLV-III clones were determined in order to estimate the level and location of variation within 3'orf, to gain some insight into the function of its protein product. Newly determined sequences are reported for 3'orf of two unintegrated clones of HTLV-III and three cDNA clones made from virion RNA derived from the same cell line infected with pooled blood samples of different patients with AIDS or AIDS-related complex symptoms (ARC). In addition, sequences for 3'orf were derived from an unintegrated viral clone derived from a different cell line infected with a distinct isolate from a single patient. These sequences are compared to those previously reported for six other viral clones. Sequences of 3'orf differ among clones by 1.1-10.4% bp and 2.4-17.0% of predicted amino acids. This represents significantly greater sequence variation than is found in the entire genome on average. Moreover, a functional proviral clone has a termination codon at amino acid residue 124 of this open reading frame. This raises questions concerning the structure, and regulation of expression of the protein encoded by 3'orf.