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. 1998 Sep;72(9):7459-66.
doi: 10.1128/JVI.72.9.7459-7466.1998.

Sequence analysis of Mus dunni endogenous virus reveals a hybrid VL30/gibbon ape leukemia virus-like structure and a distinct envelope

G Wolgamot  1 , L Bonham, A D Miller
Affiliations

Sequence analysis of Mus dunni endogenous virus reveals a hybrid VL30/gibbon ape leukemia virus-like structure and a distinct envelope

G Wolgamot et al. J Virol. 1998 Sep.

Abstract

Mus dunni endogenous virus (MDEV) can be activated from M. dunni cells by exposing the cells to hydrocortisone or 5-iodo-2'-deoxyuridine. Interference analysis has revealed that MDEV uses a receptor for cell entry that is different from those used by other murine retroviruses. The entire genome has now been sequenced, revealing a long terminal repeat (LTR)-gag-pol-env-LTR structure typical of simple retroviruses of the murine leukemia virus genus, with no additional open reading frames between env and the 3' LTR. The LTRs and other noncoding regions of MDEV are most closely related to those of VL30 elements, while the majority of the coding sequences are most closely related to those of gibbon ape leukemia virus. MDEV represents the first example of a naturally occurring, replication-competent virus with sequences closely related to VL30 elements. The U3 region of MDEV contains six nearly perfect 80-bp repeats and the beginning of a seventh, and the region expected to contain the packaging sequence contains approximately four imperfect 33-bp repeats. The receptor specificity domains of the envelope are unique among retroviruses and show no apparent similarity to regions of known proteins.

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Figures

FIG. 1
FIG. 1
Genomic structure of the proviral form of MDEV. (A) Recombinant structure of MDEV. The sequences of a VL30 element and of the MDEV and GALV genomes were aligned by using the MACAW program; the alignment at the putative breakpoint regions is shown. The recombinations are presumed to have occurred in the homologous regions shown in the shaded boxes. S.D., putative splice donor; S.A., putative splice acceptor; CTG, start codon of the extended glycosylated Gag; ATG, start codon of the nonglycosylated Gag. (B) Repeated regions of MDEV. Repeats A are nearly perfect, so only one copy is shown; the nucleotide A indicated in boldface is a C in the sixth repeat. Repeat A has a consensus retinoic acid binding site DR5, consisting of the underlined imperfect direct repeats separated by five spaces. Repeats B are perfect repeats, so only one copy is shown. The first copy of repeat B overlaps the U5-PBS boundary. Repeat C is imperfect, so all four copies are shown, with differences indicated in boldface; these 33-bp repeats are within the coding region of the extended glycosylated Gag. Repeat C has an underlined sequence similar to a sequence found in corresponding repeats of VL30 elements. CTG indicates the start codon of the glycosylated Gag, and ATG indicates the start codon of the nonglycosylated Gag.
FIG. 2
FIG. 2
The MDEV U3 region defines a fifth VL30 group. The phylogenetic tree is based on the nucleotide sequences of the U3 regions of VL30s and MDEV. The sequences are indicated by GenBank locus names. The VL30 BVL-1, which was compared to MDEV in Fig. 1A, is indicated here as MMBVL1 in group III. The four VL30 groups defined by Nilsson and Bohm (29) are indicated, along with some additional VL30 sequences, and the MDEV U3 defines a fifth group. Five of the perfect 80-bp repeats of the MDEV U3 region were eliminated prior to the alignment to make the U3 regions approximately the same size. The alignment, phylogenetic tree, and bootstrap analysis were performed with the Clustal W program, and the tree was drawn with the TreeView program. All major branchpoints between VL30 groups have confidence values of >98% except for the branchpoint that indicates that MDEV is most closely related to group 1, which was observed in 638 of 1,000 trials.
FIG. 3
FIG. 3
Differences between the MDEV and GALV sequences are consistent with a proposed model of a GALV pseudoknot. The sequences start at the pol stop codon. In this figure and in the text referring to this figure, position 1 is defined as the nucleotide immediately downstream of the stop codon. Hydrogen bonding is indicated by dots, and sequence differences are shown in boldface, with boxes drawn around differences in the proposed hairpins. The GALV pseudoknot is redrawn from reference , and the MDEV pseudoknot has been drawn by analogy.
FIG. 4
FIG. 4
Phylogenetic trees based on Pol (A) and Env (B) proteins. The protein alignments, phylogenetic trees, and bootstrap analyses were performed with the Clustal W program, and the trees were viewed by using the TreeView program. (A) Tree based on PR-RT regions of Pol proteins. Only those positions of the alignment with no gaps were used to create the phylogenetic tree. All major branchpoints had confidence values of >98%, as measured by bootstrap analysis, except for branchpoints among the closely related members of the mouse virus group at the left. (B) Tree based on entire Env proteins. Viruses observed to share receptors in at least one cell type are grouped together in ovals, and the receptor is indicated in the cases where it is known. Note that feline leukemia virus type B (FeLV-B) belongs to the phosphate transporter group but cannot be included in that oval in a two-dimensional tree. MDEV and RD114 were not grouped due to the inconsistent nature of the interference observed in G355 cells. A phylogenetic tree created by excluding positions with a gap for any sequence was nearly identical. All major branchpoints had confidence values of >97%, as measured by bootstrap analysis, except for branchpoints indicated by the number of trials of the 1,000 that produced the displayed branchpoint. Abbreviations: AKV, AKR mouse ecotropic virus; BaEV, baboon endogenous virus; CASBRE, Casitas brain ecotropic virus; FrMLV, Friend MLV; NZB, New Zealand black xenotropic virus; RadMLV, radiation MLV; SNV, spleen necrosis virus; SRV-1, simian retrovirus type 1; SSAV, simian sarcoma-associated virus.
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