Nucleotide sequence of human endogenous retrovirus genome related to the mouse mammary tumor virus genome

Abstract

We determined the complete nucleotide sequence of the human endogenous retrovirus genome HERV-K1O isolated as the sequence homologous to the Syrian hamster intracisternal A-particle (type A retrovirus) genome. HERV-K1O is 9,179 base pairs long with long terminal repeats of 968 base pairs at both ends; a sequence 290 base pairs long, however, was found to be deleted. It was concluded that a composite genome having the 290-base-pair fragment is the prototype HERV-K provirus gag (666 codons), protease (334 codons), pol (937 codons), and env (618 codons) genes. The size of the protease gene product of HERV-K is essentially the same as that of A-and D-type oncoviruses but nearly twice that of other retroviruses. A comparison of the deduced amino acid sequences encoded by the pol region showed HERV-K to be closely related to types A and D retroviruses and even more so to type B retrovirus. It was noted that the env gene product of HERV-K structurally resembles the mouse mammary tumor virus (type B retrovirus) env protein, and the possible expression of the HERV-K env gene in human breast cancer cells is discussed. Recently, human endogenous retrovirus genomes, some homologous to mammalian type B (2, 3, 8, 42) or type C (1, 18, 21, 22, 28) retroviruses or to retrovirus proviruses of an unidentified type (16), were isolated and characterized. However, the types, structures, and functions of human endogenous retroviruses and their causal relationships to human cancer have yet to be fully clarified. Intracistemal A-particle (IAP; type A retrovirus) genomes are moderately repetitive endogenous retrovirus genomes interspersedly present in rodents such as mice, rats, and Syrian hamsters (15). Our recent determination of the complete nucleotide sequence of a Syrian hamster IAP genome

Expressional activation and functional roles of human endogenous retroviruses in cancers

“…However, most open reading frames (ORFs) of the coding genes in HERVs have been degraded by deletions or mutations during evolution as part of the human genome, 3 and only very few of them retain all structural features necessary for viral replication. 4 In contrast to the coding genes, many HERV LTRs retain their potential to regulate gene transcription with the viral promoter, enhancer, and polyadenylation signals. 5 Physiological expression of HERV-H elements has been observed in embryonic stem cells.…”

“…5,6 The placenta has some peculiarities in the expression of all kinds of HERVs, 1,2 for which lower methylation content in the genome and some unique properties in epigenetic gene regulation may contribute to this phenomenon. 4 However, in more circumstances, aberrant expression of HERVs is associated with a wide range of diseases, including cancers, fetal malformations, and autoimmune diseases. [7][8][9][10] HERVs have been investigated in a large number of autoimmune disorders due to their role in innate and adaptive immunity based on molecular mimicry.…”

Sensitive Detection of Viral Transcripts in Human Tumor Transcriptomes

“…Additionally, known tumor viruses such as high-risk HPV strains, EBV, and MCPyV selectively transcribe their genome during viral latency (HPV: E6/7 [80,81], EBV: EBNA1/2 [82][83][84], MCPyV: large T antigen [31,85]), thus generating only low abundances of tens (MCPyV [31]) to hundreds (KSHV [86], EBV [87]) of transcripts per cell. Last, transcription of human oncogenic factors modulated by viral [88] or endogenous [89,90] retroviral promoters as well as 'hit-and-run' mechanisms of viral oncogenesis that imply loss of viral material [91,92] may predispose cells to transformation without requiring maintenance of viral transcripts.…”

HERV‐K(HML‐2), a seemingly silent subtenant – but still waters run deep

“…Divergence times were estimated by (14,220). The times of integration were calculated by (5,6,(221)(222)(223)(224)(225)(226)(227). regions whose sequences were not available in earlier human genome assemblies.…”