Identification of a Rev-related protein by analysis of spliced transcripts of the human endogenous retroviruses HTDV/HERV-K

Abstract

The human endogenous retrovirus family HTDV/HERV-K codes for the viral particles observed in teratocarcinoma cell lines. Two types of proviral genomes exist; these differ in the presence or absence of a stretch of 292 nucleotides. This sequence comprises the amino-terminal part of the env gene, the putative signal peptide, which overlaps in part with the carboxy terminus of the pol gene. Type 2 genomes containing this sequence presumably more closely reflect the structure of the infectious, replication-competent retrovirus ancestors of the HERV-K family than do type 1 genomes that lack the sequence. In human teratocarcinoma cell lines, both variants are expressed. Type 1 genomes, in which pol and env genes are fused, are deficient in splicing. Type 2 transcripts are spliced to subgenomic env mRNA and smaller messages. A doubly spliced transcript encodes a short open reading frame, preliminarily designated cORF (R. Löwer, K. Boller, B. Hasenmeier, C. Korbmacher, N. Mueller-Lantzsch, J. Löwer, and R. Kurth, Proc. Natl. Acad. Sci. USA 90:4480-4484). The genomic organization of cORF resembles that of nonprimate lentivirus rev genes: the first exon comprises nearly the entire signal peptide of env, and the second exon is derived from a different reading frame in the 3 part of the genome. A nucleolar localization signal, which is also a putative RNA binding domain, as well as a sequence with similarities to the Rev effector domain consensus sequence is present in the first exon. Secondary structure analysis reveals similarities to basic helix-loop-helix proteins. cORF is a small protein with an apparent molecular mass of 14 kDa which accumulates in the nucleolus as has been described for Rev proteins.

Identification of diverse full-length endogenous betaretroviruses in megabats and microbats

“…Mammalian cells restrict the export of intron containing mRNA from the nucleus to the cytoplasm, and betaretroviruses have been found to utilize two different mechanisms to circumvent this restriction and export unspliced genomic RNA and singly-spliced env mRNA. The Type B betaretrovirus MMTV, and the HERV-K endogenous retroviruses are known to use Rem and Rec, respectively, which are HIV Rev-like export proteins, that possess equivalent mechanisms of action [17,[50][51][52]. The Type D betaretroviruses MPMV and SRV make use of the cis-acting CTE, which in the absence of a retroviral accessory protein, recruits cellular proteins to effect nuclear export of intron containing viral RNA [22,23].…”

Human endogenous retrovirus (HERV)‐K transcripts in germ cell and trophoblastic tumours

“…It will be of particular interest to extend the studies to non-structural proteins potentially encoded by HERV-K genomes. Spliced mRNA homologous to the Rev protein of the human immunodeficiency virus HIV-1 was recently demonstrated in teratocarcinoma cell lines (16). Such proteins may have functions such as transcription factors and may influence growth and phenotypic properties of HERV-K expressing cells.…”

Expressional activation and functional roles of human endogenous retroviruses in cancers

“…The two representative proteins of HERV-K, Np9 and Rec, which are encoded by env gene with the presence or absence of a 292-bp deletion, have been intensively studied for their possible role in human cancers. 49,50 Both Np9 and Rec interact with the promyelocytic leukemia zinc finger protein (PLZF) tumor suppressor, abrogating the transcriptional repression of the c-myc protooncogene by PLZF and ultimately promoting cell proliferation. 51 Zhao et al observed that the HERV-K env protein was expressed in the majority of primary breast tumors.…”