Distribution of human endogenous retrovirus HERV-K genomes in humans and different primates

Steinhuber, Sabine; Brack, M.; Hunsmann, Gerhard; Schwelberger, H. G.; Dierich, Manfred P.; Vogetseder, Werner

doi:10.1007/bf00207377

Cited by 77 publications

(61 citation statements)

References 33 publications

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“…26 In turn, the lower primates also do not contain endogenous retroviruses of the HERV-K family. 49 Some proteins of endogenous retroviruses have acquired essential functions in humans; for instance, syncytin encoded by HERV-W is involved in the generation of the syncytiotrophoblast layer during pregnancy. 50 The RG-repeat of EBNA2 could represent the adaptation of the virus to the host cell to counteract the potential toxic effects of elevated LMP1 expression.…”

Section: Infectious Causes Of Cancermentioning

confidence: 99%

The NP9 protein encoded by the human endogenous retrovirus HERV‐K(HML‐2) negatively regulates gene activation of the Epstein‐Barr virus nuclear antigen 2 (EBNA2)

Gross

Barth

Pfuhl

et al. 2011

Intl Journal of Cancer

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Epstein-Barr virus (EBV) is a human tumour virus that efficiently growth-transforms primary human B-lymphocytes in vitro. The viral nuclear antigen 2 (EBNA2) is essential for immortalisation of B-cells and stimulates viral and cellular gene expression through interaction with DNA-bound transcription factors. Like its cellular homologue Notch, it associates with the DNA-bound repressor RBPJj (CSL/CBF1) thereby converting RBPJj into the active state. For instance, both EBNA2 and Notch activate the cellular HES1 promoter. In EBV-transformed lymphocytes, the RNA of the NP9 protein encoded by human endogenous retrovirus HERV-K(HML-2) Type 1 is strongly up-regulated. The NP9 protein is detectable both in EBV-positive Raji cells, a Burkitt's lymphoma cell line, and in IB4, an EBV-transformed human lymphoblastoid cell line. NP9 binds to LNX that forms a complex with the Notch regulator Numb. Therefore, the function of NP9 vis-à-vis Notch and EBNA2 was analysed. Here, we show that NP9 binds to EBNA2 and negatively affects the EBNA2-mediated activation of the viral C-and LMP2A promoters. In contrast, NP9 did neither interfere in the activation of the HES1 promoter by Notch nor the induction of the viral LMP1 promoter by EBNA2. In an electrophoretic mobility shift analysis, NP9 reduced the binding of EBNA2 to DNA-bound RBPJj by about 50%. The down-regulation of EBNA2-activity by NP9 might represent a cellular defence mechanism against viral infection or could, alternatively, represent an adaptation of the virus to prevent excessive viral protein production that might otherwise be harmful for the infected cell.

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Section: Infectious Causes Of Cancermentioning

confidence: 99%

The NP9 protein encoded by the human endogenous retrovirus HERV‐K(HML‐2) negatively regulates gene activation of the Epstein‐Barr virus nuclear antigen 2 (EBNA2)

Gross

Barth

Pfuhl

et al. 2011

Intl Journal of Cancer

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“…In addition, about 10,000 solitary LTRs are scattered throughout the human genome (16). HTDV/ HERV-K related sequences can be traced back to the time of divergence of Old and New World monkeys (15,32,33). The genomic distribution of HTDV/HERV-K proviruses appears to be nonrandom (34,35 (30,36).…”

Section: Htdv/herv-k a Family Coding For Viral Particlesmentioning

confidence: 99%

The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences.

Löwer

Kurth

1996

Proc. Natl. Acad. Sci. U.S.A.

643

505

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“…A previous study had used Southern blot analysis to search for HERV-K content differences that might exist in the human population (12). Genomic DNA samples from 37 Caucasian and 4 Chinese individuals were examined, and only one polymorphism was found, but it was not characterized.…”

mentioning

confidence: 99%

Human endogenous retrovirus K solo-LTR formation and insertional polymorphisms: Implications for human and viral evolution

Hughes

Coffin

2004

Proc. Natl. Acad. Sci. U.S.A.

195

203

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Human endogenous retroviruses (HERVs) are a potential source of genetic diversity in the human genome. Although many of these elements have been inactivated over time by the accumulation of deleterious mutations or internal recombination leading to solo-LTR formation, several members of the HERV-K family have been identified that remain nearly intact and probably represent recent integration events. To determine whether HERV-K elements have caused recent changes in the human genome, we have undertaken a study of the level of HERV-K polymorphism that exists in the human population. By using a high-resolution unblotting technique, we analyzed 13 human-specific HERV-K elements in 18 individuals. We found that solo LTRs have formed at five of these loci. These results enable the estimation of HERV solo-LTR formation in the human genome and indicate that these events occur much more frequently than described in inbred mice. Detailed sequence analysis of one provirus shows that solo-LTR formation occurred at least three separate times in recent history. An unoccupied preintegration site also was present at this locus in two individuals, indicating that although the age of this provirus is estimated to be Ϸ1.2 million years, it has not yet become fixed in the human population.A t least 8% of the human genome is made up of endogenous retroviruses and related sequences, which form Ϸ200 distinct groups and subgroups (1-3). Most of these elements represent ancient retroviral infections, as evidenced by their wide distribution in primate species, and no infectious counterparts of human endogenous retroviruses (HERVs) are known to exist today. Many HERV elements have been found to be at identical sites in both Old World monkeys and apes, which diverged Ϸ25 million years ago (4, 5), implying that the virus that gave rise to them existed at least that long ago. As a consequence of their long residence in the genome, most HERVs have acquired numerous mutations in their coding sequences, rendering them incapable of further colonization of the genome by either reinfection or intracellular retrotransposition. More ancient proviruses have more divergent LTRs, which are identical at the time of integration and acquire mutations over time (6). Inactivation of HERV elements can occur also by solo-LTR formation, which is the result of homologous recombination between the two LTRs flanking the provirus and the subsequent deletion of the internal sequence. The vast majority of HERV elements in the human genome exist as solo LTRs (7).The elements in our genome that appear to be the most recently active belong to the HERV-K family. The oldest members of this family entered the genome before the Old World monkey-ape divergence, but HERV-K elements have undergone several periods of expansion throughout primate evolution (7,8). For example, there are many HERV-K elements that are present in the African great apes and humans but not in orangutans and the lesser apes, indicating a relatively recent integration time of 8-15 million years (4, 9)....

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Distribution of human endogenous retrovirus HERV-K genomes in humans and different primates

Cited by 77 publications

References 33 publications

The NP9 protein encoded by the human endogenous retrovirus HERV‐K(HML‐2) negatively regulates gene activation of the Epstein‐Barr virus nuclear antigen 2 (EBNA2)

The NP9 protein encoded by the human endogenous retrovirus HERV‐K(HML‐2) negatively regulates gene activation of the Epstein‐Barr virus nuclear antigen 2 (EBNA2)

The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences.

Human endogenous retrovirus K solo-LTR formation and insertional polymorphisms: Implications for human and viral evolution

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