"Hidden" dUTPase sequence in human immunodeficiency virus type 1 gp120

Abstract

A coding region homologous to the sequence for essential eukaryotic enzyme dUTPase has been identified in different genomic regions of several viral lineages. Unlike the nonprimate lentiviruses (caprine arthritis- encephalitis virus, equine infectious anemia virus, feline immunodeficiency virus, and visna virus), where dUTPase is integrated into the pol coding region, this enzyme has never been demonstrated to be present in the primate lentivirus genomes (human immunodeficiency virus type 1 [HIV-1], HIV-2, or the related simian immunodeficiency virus). A novel approach allowed us to identify a weak but significant sequence similarity between HIV-1 gp120 and the human dUTPase. This finding was then extended to all of the primate lentivirus lineages. Together with the recently reported fragmentary structural similarity between the V3 loop region and the Escherichia coli dUTPase (P. D. Kwong, R. Wyatt, J. Robinson, R. W. Sweet, J. Sodroski, and W. A. Hendrickson, Nature 393:648-659, 1998), our results strongly suggest that an ancestral dUTPase gene has evolved into the present primate lentivirus CD4 and cytokine receptor interacting region of gp120.

FIG. 1

Alignment of the human dUTPase (DUTH) sequence with consensus sequences (10) for HIV-1 subtypes A to H and group O. Sixteen positions shown in red are strictly conserved. Other consensus residues (over 50% in HIV-1) are shown in green. A question mark denotes the absence of a consensus residue. Numbering corresponds to that in reference . The V3 loop and the locations of the five previously recognized conserved motifs in dUTPases (11) are indicated above the alignment. Four of these five motifs correlate with at least one strictly conserved residue. This is also true for other primate lentivirus lineages (Fig. 2). Asterisks indicated conserved residues Asp 368 and Glu 370.

FIG. 2

Conserved positions in the pairwise alignment of human dUTPase with various HIV-1, HIV-2, and SIV gp120 sequences. The human dUTPase sequence is used as a template to visualize its relationship with gp120 sequences representative of the diversity of the primate lentiviruses (PLVs). PLV type 1 (PLV-1), HIV-1 and SIV_CPZ; PLV-2, HIV-2/SIV_SM; PLV-3, SIV_AGM; and PLV-5, SIV_SYK were used according to the nomenclature of Sharp et al. (15). Sequences for the HIV-1_B, HIV-2_A, and HIV-2_B subtype representatives are consensus sequences from the Los Alamos HIV database (10); the GenBank accession numbers for SIV_SM, SIV_CPZ, SIV_AGM, and SIV_SYK are X14307, X52154, M66437, and L06042, respectively. Conserved positions are shown in red.