The Nucleotide Sequence and Spliced pol mRNA Levels of the Nonprimate Spumavirus Bovine Foamy Virus

Abstract

We have determined the complete nucleotide sequence of a replication-competent clone of bovine foamy virus (BFV) and have quantitated the amount of splice pol mRNA processed early in infection. The 544-amino-acid Gag protein precursor has little sequence similarity with its primate foamy virus homologs, but the putative nucleocapsid (NC) protein, like the primate NCs, contains the three glycine-arginine-rich regions that are postulated to bind genomic RNA during virion assembly. The BFV gag and polopen reading frames overlap, with pro and polin the same translational frame. As with the human foamy virus (HFV) and feline foamy virus, we have detected a spliced pol mRNA by PCR. Quantitatively, this mRNA approximates the level of full-length genomic RNA early in infection. The integrase (IN) domain of reverse transcriptase does not contain the canonical HH-CC zinc finger motif present in all characterized retroviral INs, but it does contain a nearby histidine residue that could conceivably participate as a member of the zinc finger. The env gene encodes a protein that is over 40% identical in sequence to the HFV Env. By comparison, the Gag precursor of BFV is predicted to be only 28% identical to the HFV protein.

Evidence that the Human Foamy Virus Genome Is DNA

“…Thus, the most recent classification of retroviruses into seven genera (mammalian type B, mammalian type C, avian type C, type D, bovine leukemia virus-human T-cell leukemia virus, Lentivirus, and Spumavirus) is somewhat misleading, with Spumavirus being much more distantly related to the other six. While the nature of the genome of other members of the Spumavirus genus has not been characterized, both feline and bovine foamy viruses also synthesize RT from a spliced mRNA rather than as a Gag-Pol fusion protein (5,12) and therefore are likely to activate RT at a similar stage in viral maturation as HFV. However, similar analyses of the virion genomes have not as yet been done.…”

Bovine Foamy Virus: Shared and Unique Molecular Features In Vitro and In Vivo

“…BFV as a well-established infection model in life-stock animals (cattle and sheep) [13,14] BFV as the only known FV in the general human food chain (beef and dairy products) [15,16] BFV Riems as the only FV passaged exclusively on primary and homologous host cells [17,18] Integrase domain: disrupted HH-CC zinc finger and unique sequence insertion into the extreme C-terminus [19] Detailed understanding of gene expression and transactivation of a non-simian FV [20,21] RNA Pol III miRNAs, unique precursor structure and their functions [14,22,23] Extremely tight cell association and identification of residues critical for this phenotype [24][25][26] Detailed understanding of new restriction factors against FVs [27] Broad tissue tropism and gene expression in BFV-infected calves [5,28] Although a so-called prototype (and/or primate) FV exists in the literature, conserved, prototypic features, besides those basic characteristics that led to the establishment of an independent subfamily of FVs, are currently only partially known. Here, an unbiased comparison of distant FVs and their replication strategies might be worth trying to discriminate basic from deduced, secondary features.…”

“…taxnode_id=20074661) [1]. Holzschu et al [19] published the first full-length nucleotide sequence of a BFV isolate from the United States (US) in 1998. These data confirmed the overall genetic structure and coding capacity of BFV as a typical member of the FV genus (Figure 2A).…”

“…Although the sequence homology between the Bet proteins of different FVs is very low, some motifs in Bel2 are similar among the different Bet proteins [49]. The Bet proteins of the known BFV isolates [17,19,[50][51][52] are highly conserved. In PFV-infected cells, Bet was shown to fuse with Env and form a glycoprotein of~170 kDa [53], but a corresponding BFV Env-Bet fusion protein could not be detected while using a BFV Bet antiserum.…”

“…Interestingly, the equivalent position of the 898 residue in all known BFV isolates (from the United States, NC001831.1. [19], China, AY134750.1 [50], Poland, JX307861 [51,52], and Germany JX307862.1 [17,52], which only spread through cell-to-cell, is not a lysine (K), while the equivalent position is occupied by a lysine in other high titer cell-free FVs, such as SFV, FFV, and PFV. This suggests that the K898 in Env has an important role in FV cell-free transmission.…”