Analysis of the primary structure of the long terminal repeat and the gag and pol genes of the human spumaretrovirus

Abstract

The nucleotide sequence of the human spumaretrovirus (HSRV) genome was determined. The 5' long terminal repeat region was analyzed by strong stop cDNA synthesis and S1 nuclease mapping. The length of the RU5 region was determined and found to be 346 nucleotides long. The 5' long terminal repeat is 1,123 base pairs long and is bound by an 18-base-pair primer-binding site complementary to the 3' end of mammalian lysine-1,2-specific tRNA. Open reading frames for gag and pol genes were identified. Surprisingly, the HSRV gag protein does not contain the cysteine motif of the nucleic acid-binding proteins found in and typical of all other retroviral gag proteins; instead the HSRV gag gene encodes a strongly basic protein reminiscent of those of hepatitis B virus and retrotransposons. The carboxy-terminal part of the HSRV gag gene products encodes a protease domain. The pol gene overlaps the gag gene and is postulated to be synthesized as a gag/pol precursor via translational frameshifting analogous to that of Rous sarcoma virus, with 7 nucleotides immediately upstream of the termination codons of gag conserved between the two viral genomes. The HSRV pol gene is 2,730 nucleotides long, and its deduced protein sequence is readily subdivided into three well-conserved domains, the reverse transcriptase, the RNase H, and the integrase. Although the degree of homology of the HSRV reverse transcriptase domain is highest to that of murine leukemia virus, the HSRV genomic organization is more similar to that of human and simian immunodeficiency viruses. The data justify classifying the spumaretroviruses as a third subfamily of Retroviridae.

Characterization of the transcriptional trans activator of human foamy retrovirus

“…Construction of molecular clones. All HSRV constructs were derived from the previously published pHSRV-B-C11, pHSRV-H-C55, and pHSRV-BS2 proviral clones (9,20). Coordinates of HSRV sequences are given throughout relative to the site of viral transcription initiation.…”

“…Because of the lack of a clear disease association, the human spumaviruses have until recently failed to attract the high level of scientific attention accorded the more clearly pathogenic human retroviral species. However, several subgenomic molecular clones of HSRV have been isolated and sequenced (9,20). Recently, it has been shown that a full-length proviral clone of HSRV constructed from these subgenomic DNA fragments is fully infectious in tissue culture (17,27).…”

Genome Analysis and Replication Studies of the African Green Monkey Simian Foamy Virus Serotype 3 Strain FV2014

“…The genomic organization of the assembled SFVcae_FV2014 genome [17] was found to be similar to other SFVs: It had the expected structural genes (gag, pol, and env) and accessory (tas and bet) genes, an internal promoter, and long terminal repeats (LTRs) [8]. An 18-bp primer binding site (PBS) was identified at position 1713 to utilize the tRNA Lys1,2 isoacceptor for initiation of minus-strand DNA synthesis of spumaviruses [22]. The complete genomic sequence of SFVcae_FV2014 with alignment to the SFVcae_LK3 sequence is shown in Figure S1 and summarized in Table 3.…”

Foamy Viruses Are Unconventional Retroviruses

“…The prototype FV, human FV (HFV) was isolated from tissue culture cells of a human nasopharyngeal cell line of African origin (1). This isolate was the first FV to be cloned and sequenced (24,55), and an infectious molecular clone was derived (53,70). Recent work indicates that this virus is virtually identical to SFV isolated from chimpanzees, SFV type 6 (SVF-6), SFV-7, and SFV-cpz (34) (Fig.…”