Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements
Open accessAbstract
Human Endogenous Retroviruses are expected to be the remnants of ancestral infections of primates by active retroviruses that have thereafter been transmitted in a Mendelian fashion. Here, we derived in silico the sequence of the putative ancestral “progenitor” element of one of the most recently amplified family—the HERV-K family—and constructed it. This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny. We also show that this element amplifies via an extracellular pathway involving reinfection, at variance with the non-LTR-retrotransposons (LINEs, SINEs) or LTR-retrotransposons, thus recapitulating ex vivo the molecular events responsible for its dissemination in the host genomes. We also show that in vitro recombinations among present-day human HERV-K (also known as ERVK) loci can similarly generate functional HERV-K elements, indicating that human cells still have the potential to produce infectious retroviruses.
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There is no fully functional HERV-K in the human genome, but a number of HERV-K proviruses are capable of making one or several of the viral proteins.
“There is no fully functional HERV-K in the human genome, but a number of HERV-K proviruses are capable of making one or several of the viral proteins”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Dewannieux et al. 2006
The Abstract says that no HERV-K provirus able to produce infectious particles had yet been described, and that several loci have complete viral-protein coding sequences. But it does not establish that no fully functional HERV-K exists in the human genome; the Discussion says some human alleles might still be functional. (LLM, conf=0.87)
Experimental — accuracy not yet measuredRecombination between three defective HERV-K (HML2) proviruses has been shown, at least in vitro, to generate an infectious retrovirus.
“and, furthermore, recombination between three defective HERV-K (HML2) proviruses has been shown, at least in vitro, to generate an infectious retrovirus 84.”
From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [84]
Reconstruction of a consensus HERV-K (HML2) provirus by assembly and alignment of all complete but defective HERV-K (HML2) proviruses resulted in a replication-competent recombinant retrovirus.
“Interestingly, reconstruction of a consensus HERV-K (HML2) provirus by assembly and alignment of all of the complete, but defective HERV-K (HML2) proviruses resulted in a replication-competent recombinant retrovirus 84,85.”
From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [84]
Engineered recombinant HERV-K constructs that contain all open reading frames are capable of viral transmission in cell culture.
“Engineered recombinant HERV-K constructs that contain all open reading frames are capable of viral transmission in cell culture”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Dewannieux et al. 2006
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References 38 · Cited by 309
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- Authors
- Dewannieux, M., Harper, F., Richaud, A., Letzelter, C., Ribet, D., Pierron, G., & Heidmann, T.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2006-10-31
- Volume
- 16
- Issue
- 12
- Pages
- 1548-1556
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC1665638
- OpenAlex
- W2135790438
- Cited by
- 309
- References
- 38
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- Type
- posted content
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- HERV-K, human endogenous retroviruses, retroviral reactivation, retrotransposition, recombination, retroviral integration, retroviral evolution
- MeSH terms
- Amino Acid Sequence, Cell Line, Gene Amplification, Humans, Polymorphism, Genetic, Proviruses, Recombination, Genetic, Transfection, Genome, Human, Mutagenesis, Insertional, Consensus Sequence, Virus Integration, Retroelements, Evolution, Molecular, Computational Biology, Amino Acid Substitution, Endogenous Retroviruses
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