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Hematological malignant tumors (HMTs) are serious diseases that threaten human health and life with high mortality. Therefore, it is necessary to develop novel strategies for diagnosis and treatment. Human endogenous retroviruses (HERVs) have recently attracted increasing attention as potential targets for cancer diagnosis and therapy. In this study, we explored the association between HERV-K expression levels and HMTs development. Clinical data and peripheral blood samples were collected from 236 leukemia, 384 lymphoma patients, and 69 healthy controls. Quantitative polymerase chain reaction was used to detect the expression of HERV-K gag , pol , and env genes in peripheral blood mononuclear cells or different cell subpopulations. Differently expressed HERV-K genes were further tested by using deep sequencing method, and further analyzed with gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. B cell- and T cell-related cytokines in patients were also detected by enzyme-linked immunosorbent assay (ELISA). The results showed that the expression levels of the HERV-K gag , pol , and env genes in patients were significantly higher than in healthy controls. There was a correlation between the expression level of HERV-K and the clinicopathological parameters of leukemia patients. HERV-K expression was increased in the B lymphocytes of leukemia and lymphoma patients, but not in the T cells or neutrophils. The GO and KEGG analyses showed that abnormal expression of the HERV-K locus in patients affected immune regulation. The analysis of cytokines proved that the B cell-related cytokines, including interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon-gamma, were significantly decreased in patients, while the T cell-related cytokines, including IL-3, IL-12, and TNF-β, were not significantly changed. In conclusion, HERV-K genes might participate in the occurrence and development of leukemia and lymphoma, and might be biomarkers for the detection or evaluation of leukemia and lymphoma.

Human endogenous retroviruses (HERVs) can be vertically transmitted in a Mendelian fashion, are stably maintained in the human genome, and are estimated to constitute ∼8% of the genome. HERVs affect human physiology and pathology through their provirus-encoded protein or long terminal repeat (LTR) element effect. Characterization of the genomic distribution is an essential step to understanding the relationships between endogenous retrovirus expression and diseases. However, the poor characterization of human MMTV-like (HML)-8 prevents a detailed understanding of the regulation of the expression of this family in humans and its impact on the host genome. In light of this, the definition of an accurate and updated HERV-K HML-8 genomic map is urgently needed. In this study, we report the results of a comprehensive analysis of HERV-K HML-8 sequence presence and distribution within the human genome and hominoids, with a detailed description of the different structural and phylogenetic aspects characterizing the group. A total of 40 proviruses and 5 solo LTR elements for human were characterized, which included a detailed description of provirus structure, integration time, potentially regulated genes, transcription factor-binding sites, and primer-binding site features. Besides, 9 chimpanzee sequences, 8 gorilla sequences, and 10 orangutan sequences belonging to the HML-8 subgroup were identified. The integration time results showed that the HML-8 elements were integrated into the primate lineage around 35 and 42 million years ago (mya), during primates evolutionary speciation. Overall, the results clarified the composition of the HML-8 groups, providing an exhaustive background for subsequent functional studies.

Female sex hormones, the octamer-binding transcription factor 4 (OCT4), and human endogenous retroviruses (HERVs) are all involved in the development of breast cancer. However, whether there are cross talks between these factors to promote breast cancer is still unknown. Using the T47D human breast cancer cell line, we have found that estradiol and progesterone synergistically activate HERV-K through nuclear receptors. The progesterone receptor (isoform B) binds a progesterone-response element (PRE) in a long terminal repeat (LTR5HS) of HERV-K. There is another transcription factor-binding element in the LTR, the octamer motif, which is required for the hormones to activate gene transcription downstream of the LTR. Gel shift assays and co-immunoprecipitation indicate that the progesterone receptor (PR) and the OCT4 transcription factor interact on the protein level. Methylation of the PRE enhances binding of the PR. These findings help to elucidate the previously unknown cross talks among the sex hormones, OCT4, and HERVs in contributing to breast cancer proliferation and tumorigenesis, which may be useful in guiding further development of cancer therapies.

Endogenous retroviruses (ERVs), which are footprints of ancient germline infections, were inserted into the genome during the early stages of primate evolution. Human endogenous retroviruses (HERVs) occupy approximately 8% of the human genome. Although most ERV genes are defective, with large deletions, stop codons, and frameshifts in their open reading frames (ORFs), some full-length sequences containing long ORFs are expressed in several tissues and cancers. Several envelope glycoproteins that are encoded by env genes have retained some characteristics of their ancestral infectious viruses. These glycoproteins play essential physiological roles in the organs in which they are expressed. Previous studies have demonstrated the expression of ERV env at the mRNA level in cells and tissues rather than at the protein level, which is more difficult to detect. However, it is not known whether Env is functionally conserved in primates. To understand the possible role of Env in primates, we examined the expression of the env genes of four ERVs (ERV-R, -K, -W, and -FRD) at the protein as well as mRNA levels in various tissues of the rhesus monkey. The ERV env gene products were observed at moderate to high levels in each tissue that was examined and showed tissue-specific expression patterns. Our data suggest a biologically important role for retroviral proteins in healthy tissues of the rhesus monkey.

Human endogenous retroviruses (HERVs) accounting for 9% of the human genome are considered as surrogate markers for genetic instability and as a driving force of genetic variation. Moreover, they modulate regular gene activities and give rise to expression of disease-associated peptides that may serve as diagnostic markers or even targets for T cell-based immune responses. To date, no data are available on the potential link between urothelial carcinogenesis, HERV activity, and tobacco smoking, the main risk for bladder cancer. Here, we report on potential alterations in HERV transcription induced by smoking in a newly established in vitro model and in human urothelium. Normal human dermal fibroblasts were cultivated with urine from never (n = 6) and current smokers (n = 6) and transcription levels for the HERV subfamilies HERV-E 4-1, HERV-T S71-TK1, and HERV-K HML-6 were measured by quantitative real-time PCR. Tendencies toward increased mean transcript levels were detected for cells treated with urine from current smokers. Equally, activity measured in human urothelium supported an increase of HERV transcription in current smokers (n = 9) compared to never smokers (n = 4).

Numerous studies have invoked a role for retroviruses in multiple sclerosis (MS). Most have identified human endogenous retroviruses (HERVs) as possible etiological agents. The majority of HERVs originate from ancestral infection and then become progressively disabled by mutations over millions of years of primate evolution. Their presence in 100% of healthy humans, together with the paucity of functional retroviral genes, argues strongly against a causal role in disease. Recently, a new class of insertionally polymorphic HERVs has been described that is present in only a proportion of the population. One of them, HERV-K113, is notable for open reading frames for all of its genes and is found in 0-28% of humans with widespread geographic and racial variation. Thus HERV-K113 is a credible candidate for causing disease in a manner comparable to infectious retroviruses. Genomic DNA samples from 951 patients with MS were tested for the presence of the HERV-K113 allele by PCR, with their unaffected parents (n = 1902) acting as controls. HERV-K113 provirus was found in 70 out of 951 (7.36%) patients with MS and was not significantly increased compared to the combined parent group (6.52%). The results do not support an association between this endogenous retrovirus and MS. This study also emphasizes the need for large cohorts with controls for race and geographic location when examining possible links between polymorphic HERVs and disease.

Human endogenous retroviruses (HERVs) have been associated with multiple sclerosis (MS) pathogenesis. Several related HERV-W sequences have been implicated in disease occurrence and progression; the MS retrovirus (MSRV) is one such element whose envelope protein has been recently demonstrated to be involved in innate immune pathogenesis. To distinguish MSRV from other HERV-W sequences we analyzed the relative abundance of individual HERV-W env sequences by employing a real-time PCR approach using specific oligonucleotide primers and tissue samples from MS and non-MS patients. Our analyses reveal that ERVWE1 env-encoding DNA and RNA exhibited increased detection (p < 0.05) and expression (p < 0.01) in the brains of MS patients. Similarly, ERVWE1 env transcripts were inducible in glial cells (p < 0.05), while comparable changes in MSRV abundance were not observed. These results indicate that individual HERVs might have distinct roles in MS pathogenesis.

The viral kinetics of HERV-K in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) is not unknown. HERV-K kinetic modeling may provide insight into factors altering the effectiveness of HAART in suppressing HIV-1 burden. We conducted a longitudinal study measuring the HERV-K RNA titers in four patients with successful HIV-1-suppressive HAART and in six patients undergoing HAART failure. HERV-K titers were usually undetectable in patients with successful HAART, and when detected, HERV-K titers remained below 5000 copies/ml. On the other hand, HERV-K RNA was consistently detected in patients who failed to respond to HAART before and after HIV-1 rebounds (p < 0.001). Elevated HERV-K RNA titers frequently preceded HIV-1 rebounds. These results suggest that HERV-K viral load may predict HIV-1 reactivation. HERV-K RNA testing might be clinically useful in predicting the onset of HIV-1 resistance due to suboptimal antiretroviral drug levels and/or poor adherence to treatment.

Antibodies to HERV-K antigens have been linked to HIV-1 infection and expression of HERV-K proteins generates T-cell cytotoxic responses in many cancers. HERV-K RNA and protein abundance was measured in HIV-1-infected and control cells. In vitro exposure of HIV-1 laboratory-adapted and primary isolates on U87MG cells increased the expression of HERV-K RNA in a dose-dependent manner. HERV-K RNA and protein burdens were significantly increased in HIV-1-producing H9 cell lines compared to H9 cells. The expression of HERV-K was synergistically increased in HIV-1-infected PBMCs after stimulation with PMA/ionomycin. Furthermore, the expression of HERV-K in PBMCs, and particularly in CD4(+) T cells, was higher in HIV-1 patients compared to control subjects. The expression of HERV-K might be related to HIV-1 pathogenesis and AIDS-associated cancers.

Although human endogenous retroviruses (HERVs) constitute 8% of the human genome, their role(s) in health and disease remain uncertain. Nonetheless, increased HERV gene activity has been reported in neuroinflammatory diseases such as multiple sclerosis (MS). The human endogenous retrovirus (HERV)-W7q envelope gene encodes a glycosylated envelope protein, syncytin-1, which is expressed in many tissues. Analysis of HERV envelopes (env) revealed a selectively increased abundance of syncytin-1 encoding RNA in brains from patients with MS (p<0.01) relative to non-MS patients. However, HERV env expression from blood-derived leukocytes did not differ between groups. A quantitative PCR-based assay for syncytin-1 RNA showed that median viral RNA levels were higher in brains of MS patients (5.0 log10 copies/microg RNA) relative to non-MS patients (4.6 log10 copies/microg RNA) (p<0.05). Median syncytin-1 DNA levels in MS brains (9.8 log10/microg DNA) were higher than non-MS brain tissue (7.9 log10/microg DNA) (p<0.001) without evidence of new integration events. In contrast, there were no differences in syncytin-1 RNA copy numbers between groups in both CSF (non-MS: 5.0 log10/ml versus MS: 3.8 log10/ml) and plasma (non-MS: 5.033 log10/ml versus MS: 2.9 log10/ml). These observations emphasize the selective induction of syncytin-1 in brain tissue of MS patients but also illustrate the complex dynamics of this retroelement in neuroinflammatory processes.

To investigate the biological roles of human endogenous retrovirus-R (HERV-R) in vivo, we established transgenic rats carrying the full sequence of the viral genome with control of its own long terminal repeat promoter. The Env protein was expressed on the surface of the epidermis of fetal HERV-R transgenic rats on day 10 of gestation. The epidermal Env expression disappeared by day 18 of gestation. After day 18 of gestation, the Env protein was detected in the prickle layer of the esophageal epithelium of transgenic rats. Interestingly, it was not detected in the basal layer of the epithelium, and the expression in the granular layer was weaker than in the prickle layer. These findings suggest that expression of HERV-R is linked not only to the development but also to the differentiation of squamous cells. Next, we examined alterations in the expression of the HERV-R env gene in cultured human squamous cells after exposure to all-trans retinoic acids (ATRA). The env expression was increased by ATRA in a dose-dependent manner, while the expression of transglutaminase 1 (TGM1), a terminal marker for squamous differentiation, was decreased. TGM1 is expressed in the granular layer of the squamous epithelium, and ATRA suppresses the differentiation of cultured squamous cells. Thus, these in vitro data also suggest that HERV-R expression is regulated by a mechanism closely related to the differentiation of squamous cells. This study is the first to demonstrate the association of HERV-R expression and differentiation of squamous cells.

Approximately 8% of the human genome sequence is composed by human endogenous retroviruses (HERVs), most of which are defective. HERV-K(HML-2) is the youngest and most active family and has maintained some proviruses with intact open reading frames (ORFs) that code for viral proteins that may assemble into viral particles. Many HERV-K(HML-2) sequences are polymorphic in humans (present in some individuals but not in others) and probably many others may be unfixed (not inserted permanently in a specific chromosomal location of the human genome). In the present study HIV-1 and HCV-1-positive plasma samples were screened for the presence of HERV-K(HML-2) RNA in an RT-PCR using HERV-K pol specific primers. HERV-K(HML-2) viral RNA sequences were found almost universally in HIV-1(+) plasma samples (95.33%) but were rarely detected in HCV-1 patients (5.2%) or control subjects (7.69%). Other HERV-K(HML-2) viral segments of the RNA genome including gag, prt, and both env regions, surface (su), and transmembrane (tm) were amplified from HERV-K pol-positive plasma of HIV-1 patients. Type 1 and type 2 HERV-K(HML- 2) viral RNA genomes were found to coexist in the same plasma of HIV-1 patients. These results suggest the HERV-K(HML-2) viral particles are induced in HIV-1-infected individuals.

Endogenous retroviruses (ERVs) probably originate from ancient germ cell infections by exogenous retroviruses. A high expression of retroviruses in reproductive tissue increases the risk of viral transmission to germ line cells. We therefore investigated the expression of human ERVs (HERVs) in normal endometrium, endometriosis, normal ovaries, and ovarian cancer. Four real-time PCRs (QPCRs) for HERV-E, HERV-I/T, HERV-H, and HERV-W, respectively, and an expression control gene were used. HERV-E RNA expression was significantly higher in endometriotic tissue (average, SD) than in normal endometrium (average, SD), both measured as ratios versus control gene expression and as. HERV-E and HERV-W RNA were higher in normal ovarian tissue than in ovarian cancer. This illustrates that HERV expression is not automatically higher in malignant tissues. The other HERV PCRs did not show expression patterns as distinctive as HERVE and HERV-W in the two kinds of reproductive tissue. A small number of candidate HERV-E loci from which the transcription took place were identified by sequencing of amplimers. The role of HERV-E and HERV-W in endometriosis merits further investigation.

Human endogenous retrovirus K (HERV-K) is distinctive among the retroviruses that comprise about 8% of the human genome in that multiple HERV-K proviruses encode full-length viral proteins, and many HERV-K proviruses formed during recent human evolution. HERV-K gag proteins are found in the cytoplasm of primary tumor cells of patients with seminoma. We identified HERV-K-specific T cells in patients with a past history of seminoma using the interferon-gamma ELISPOT assay and an MHC-HERV-K peptide-specific tetramer. A minority of apparently healthy subjects without evident germ cell tumors also made HERV-K-specific T cell responses. In summary, we detected T cell reactivity to HERV-K peptides in both past seminoma patients and a minority of apparently healthy controls.

Endogenous retroviral sequences resulting from ancient retrovirus infections of germline cells account for up to 8% of the human genome. Most of these sequences are highly truncated, have been altered by mutations, and do not encode functional genes. However, some members of the human endogenous retrovirus (HERV)-K family are remarkably intact and display high genetic homology to mouse mammary tumor virus (MMTV), a retrovirus causing breast cancer in mice. Two full-length HERVs (K113 and K115) have been reported to show insertional polymorphism. We used PCR to investigate the presence of these two HERVs in 102 female breast cancer patients and an equal number of age-matched controls with no history of malignancy (age range: 25-92 years). The two groups showed no significant difference in frequency (HERV-K113, 16.7% vs. 12.7%; HERV-K115, 4.9% vs. 9.8%) and no apparent association with histology, age at diagnosis, receptor status, HER-2/neu status, or TNM stage at diagnosis. This suggests that the two HERV-Ks do not play a pathogenetic role in the majority of breast cancer patients, though they may be involved in a minority of patients. The results are discussed.

The transmissibility of the human endogenous retrovirus HERV-H/RGH-2 was investigated by marker rescue: intraspecies transmission of HERV-H/RGH-2 retrovirus particles was attempted by cocultivation of virion-producing, long-term cell cultures spontaneously formed from peripheral blood mononuclear cells from several multiple sclerosis patient cultures with a retroviral vector construct-harboring cell line. Transmissibility was assessed by assays for productive infection (reverse transcriptase activity), and assays for rescue of the retroviral vector construct in indicator cells. Our studies show that the human endogenous retrovirus HERV-H/RGH-2 is transmissible, albeit at a very low level. The human endogenous retrovirus HERV-H/RGH-2 is associated with multiple sclerosis (MS). Previously, we demonstrated sequence variants of the human endogenous retrovirus HERV-H family in virion form, by applying RT-PCR to virion RNA from the supernatants of long-term MS cell cultures, and to the particulate fraction of a series of MS patient plasma samples.

Human endogenous retroviruses (HERVs) are estimated to represent at least 1% of the human genome. An HERV-H env SU sequence (HERV-H19) was used to screen the high-throughput (htgs) and nonredundant (nr) databases for other HERV-H SU open reading frames (ORFs) and thus possible functional proteins. Using PCR with primers derived from HERV-H19 SU, we also obtained several new sequences with ORFs from a human DNA sample. In a phylogenetic analysis, ORF-containing sequences clustered with HERV-H sequences from chromosomes 1 and 2. SU ORF- and non-SU ORF-containing elements had about the same difference between 5' and 3' long terminal repeats (LTRs) (about 4%), indicating a similar time of integration. SU ORF sequences had a moderately high number of synonymous-versus-nonsynonymous mutations, which indicates a selection for maintenance of the HERV-H SU ORFs.

A new human endogenous retroviral family (HERV-W) has been described that is related to multiple sclerosis-associated retrovirus (MSRV) sequences that have been identified in particles recovered from monocyte cultures from patients with multiple sclerosis. Using the PCR approach with a human monochromosomal somatic cell hybrid DNA panel, 24 pol fragments of the HERV-W family from chromsomes 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 20, 21, X, and Y were identified and analyzed. They showed a high degree of nucleotide sequence similarity (89.3-91.3%) with that of the HERV-W. Translation of the pol fragments showed no frameshift and termination codon by deletion/insertion or point mutation in some clones: HWP4-1, HWP4-2 from chromosome 4, and HWPX-1 from chromosome X. Phylogenetic analysis of the HERV-W family indicates that the pol fragments have evolved independently among chromosomes or represent separate integration events during primate evolution.

Long terminal repeat (LTR) elements of human endogenous retrovirus (HERV-K) may have contributed to disease-associated structural change or genetic variation in the human genome. The LTR elements have been found to be coexpressed with sequences of closely located genes. We identified seven HERV-K LTR elements from mRNA of human cancer cells (HepG2, MCF7, and SiHa), using the RT-PCR approach. Four of them are closely related to the human-specific HERV-K LTR elements with a high degree of sequence homology in a neighbor-joining phylogenetic tree. The data suggest that recently proliferated HERV-K LTR elements are expressed actively in various cancer cells. These HERV-K LTR elements deserve further investigation as potential leads in the treatment of human cancer.

A new human endogenous retroviral family (HERV-W) has been described that is related to multiple sclerosis-associated retrovirus sequences that have been identified in particles recovered from monocyte cultures from patients with multiple sclerosis. Using the polymerase chain reaction approach with a human monochromosomal somatic cell hybrid DNA panel, 15 env fragments of the HERV-W family from chromosomes 1, 3, 4, 5, 6, 7, 12, 14, 17, 20, and X were identified and analyzed. These env fragments showed a high degree of nucleotide sequence similarity (91.6-99.6%) to that of HERV-W. Translation of the env fragments showed no frameshift and termination codons by deletion/insertion or point mutation in some clones (W-1-1, W-3-8, W-4-1, W-7-1, W-14-1, W-17-5, W-20-9, and W-X-3). Phylogenetic analysis of the HERV-W family indicates that the HERV-W env fragments divided into five groups through evolutionary divergence in the primate genome. In group IV, a clone (W-12-2) on chromosome 12 shared 100% sequence identity with a clone (W-17-5) on chromosome 17, suggesting either a retrotransposition or a chromosomal translocation in the last 2 to 5 million years.

A new human endogenous retroviral family (HERV-F) has been identified from human chromosome 7q31.1-q31.3 that was identical to the XA34 cDNA clone isolated from a human glioma cDNA library with an ERV-9 env probe. We investigated pol gene sequences of the HERV-F family from a human monochromosomal DNA panel and analyzed these with HERV-F. The pol gene sequences of the HERV-F family were detected on chromosomes 3, 6, 7, 10, 11, 14, 19, 20, X, and Y as examined by PCR. Thirty-six pol gene sequences identified from the human chromosomes have a high degree of sequence similarity (80-99%) with that of the HERV-F. Phylogenetic analysis of pol gene sequences distinctively showed four groups, indicating that the HERV-F family could be amplified at least four times after the original integration into the human genome or represent integration events separately during hominid evolution. One clone (HFY-3) on chromosome Y shared 100% sequence identity with a clone (HF19-2) on chromosome 19, and a clone (HF20-6) on chromosome 20 suggests either a recent retrotransposition or a chromosomal translocation. The history of endogenous retroviral sequences may contribute to an understanding of evolutionary change in human genomes.

Some genomic elements of the multicopy HERV-W endogenous retroviral family have been previously identified in databases. One of them, located on chromosome 7, contains a single complete open reading frame (ORF) putatively encoding an envelope protein. We have experimentally investigated the genomic complexity and coding capacity of the HERV-W family. The human haploid genome contains at least 70, 100, and 30 HERV-W-related gag, pro, and env regions, respectively, widely and heterogeneously dispersed among chromosomes. Using in vitro transcription-translation procedures, three putative HERV-W gag, pro, and env ORFs were detected on chromosomes 3, 6, and 7, respectively, and their sequences analyzed. A 363 amino acid gag ORF containing matrix and carboxy-terminal truncated capsid domains encoded a putative 45-kDa protein. No gag-pro ORF was found, but a pro sequence containing a DTG active site was detected. Finally, the previously described 538 amino acid HERV-W env ORF, located on chromosome 7, was shown to be unique and encoded a putative 80-kDa glycosylated protein. Proteins of molecular mass identical to the one obtained by an in vitro transcription-translation procedure were detected in human placenta, using anti HERV-W Gag- and Env-specific antibodies. The absence of an HERV-W replication-competent provirus versus the existence of HERV-W-related Gag and Env proteins in healthy human placenta is discussed with respect to particle formation, physiology, and pathology.

We have developed a highly sensitive, universal assay that allows detection as well as identification of all known retroviral reverse transcriptase (RT)-related nucleic acids in a biological sample by a single two-step experiment. The assay combines polymerase chain reaction (PCR) and reverse dot-blot hybridization (RDBH), using an array of immobilized synthetic retrovirus-specific oligonucleotides and two sets of mixed oligo primers (MOPs). These primers were derived from highly conserved motifs found in all known reverse transcriptase genes. The PCR/RDBH assay was used for qualitative analyses of human endogenous retrovirus (HERV) transcription in peripheral blood mononuclear cells (PBMCs) and in particles released by the human mammary carcinoma-derived cell line T47D. Sensitivity was further demonstrated by detection of down to 10 copies of pig endogenous retrovirus (PERV) DNA in human cDNA samples. Therefore, this assay is particularly useful for the identification of retroviral sequences in xenografts as well as in recipients of xenografted tissues and organs. Moreover, it is a valuable tool to detect retroviral transcripts and particles in cell cultures used for production of therapeutic polypeptides. The assay is further suitable for monitoring vector preparation used in human gene therapy to exclude transfer of copackaged endogenous retroviruses into target cells.

A new type C retrovirus-related endogenous pol sequence (ERV-FTD) found to be occasionally copackaged in retrovirus-like particles released by the human mammary carcinoma cell line T47D was used to screen a human genomic library (Seifarth W, Skladny H, Krieg-Schneider F, Reichert A, Hehlmann R, and Leib-Mösch C: J Virol 1995;69:6408-6416). The DNA sequence of one full-length clone now reveals a human endogenous proviral sequence (HERV) of 4190 bp in length comprising a 5' LTR (489 bp) and regions with 37 and 74% overall amino acid homology to RTVL-Ia gag and pol genes, respectively. About 35 related elements were found to be distributed on all human chromosomes except 16, 17, and Y. Sequence comparisons with Mo-MuLV and various type C-related HERVs suggest that despite a proline primer-binding site this novel HERV element, now named HERV-IP-T47D, can be assigned to one family together with known HERV-I elements. Phylogenetic analyses of 5 proviral and 25 solitary LTR sequences confirmed the existence of two distinct but closely related subgroups of the HERV-IP superfamily in the primate genome. In contrast to most known HERV-families, the evolutionary age of HERV-IP elements dates back prior to the divergence of New and Old World monkeys. Despite their old age, members of the HERV-IP family are still transcriptionally active and were found to be highly expressed in specific human tissues such as liver and kidney.

A novel human endogenous retrovirus, HERV-W, has been characterized on the basis of multiple sclerosis-associated retrovirus (MSRV) probes. We have analyzed the phylogenetic distribution of HERV-W in humans and other primate species. As HERV-W presents a C/D chimeric nature and is largely composed of deleted elements, Southern blots were performed using gag, pol, env, and LTR probes. The relative complexities observed for gag, pol, env, and LTR regions were similar in humans, apes, and Old World monkeys, the minimal number of bands observed after Southern blot analysis being 25, 50, 10, and at least 100, respectively. The HERV-W family entered the genome of catarrhines more than 25 million years ago.