PubMed · 11042855
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Iu B Lebedev. [Endogenous retroviruses: possible role in human cell function].. https://pubmed.ncbi.nlm.nih.gov/11042855/
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Endogenous retroviruses (ERVs) are dynamically regulated across the lifespan and can function as context-dependent components of host gene-regulatory networks. During embryonic development, selected ERV-derived elements are co-opted to support zygotic genome activation, lineage specification, and placental development. In adult tissues, ERV-derived sequences can contribute to tissue and immune homeostasis, whereas potentially disruptive ERV activity is constrained by epigenetic mechanisms. During regeneration and somatic cell reprogramming, ERV and broader transposable-element programs undergo transient, locus-specific remodeling. In aging, the weakening of epigenetic and nuclear restraint can promote aberrant ERV derepression, inflammation, and functional decline. This review summarizes the diverse roles of ERVs across these contexts and discusses the challenges of defining locus-specific functions, resolving repetitive sequences, and developing safe ERV-targeted interventions.
Endogenous retroviruses (ERVs), remnants of ancient viral infections integrated into host genomes, serve as invaluable molecular fossils for studying viral evolution. In this study, we performed a genomic analysis of the Chinese pangolin (Manis pentadactyla), identifying novel full-length endogenous retroviruses, designated as Manis pentadactyla ERVs (MPERVs). MPERVs span three retroviral genera: Alpha-, Beta-, and Gamma-retroviruses. Using genomic screening and phylogenetic analysis, we classified MPERVs and reconstructed their evolutionary history, uncovering evidence of complex recombination events and cross-species transmission. Estimated insertion times for MPERVs range from very recent to 18.38 million years ago. MPERVs exhibit diverse structural features, notably including conserved retroviral domains and functional motifs and highlighting their preservation across extensive evolutionary periods. These findings shed light on the evolutionary dynamics of ERVs in Chinese pangolin and suggest the potential for expanded host ranges among certain retrovirus genera.IMPORTANCEEndogenous retroviruses are unique viruses distinguished by the fact that they are retained as part of the host genome after an exogenous retrovirus infects the host. The Chinese pangolin, as a host with a long independent evolutionary history, likely holds valuable insights in its genome regarding retrovirus endogenization and transmission. In this study, we identified the footprints of exogenous retroviruses from three different genera in the pangolin genome: Alpharetrovirus, Betaretrovirus, and Gammaretrovirus. Additionally, by calculating the integration times of the pangolin's endogenous retroviruses and analyzing the domains of the three main functional proteins (GAG, POL, and ENV), we found that the insertions are relatively young. This suggests that these endogenous retroviruses infected the Chinese pangolin long before their endogenization. This study represents the exploration of endogenous retroviruses in the Chinese pangolin genome, expanding our understanding of endogenous retroviruses in mammals. Furthermore, our findings provide new evidence for the phenomenon of the cross-species transmission of retroviruses prior to endogenization.
Human endogenous retroviruses (HERVs) are proviral relics of infections that affected primates' germ line. Many HERV elements retain a residual capacity to encode transcripts and proteins that have been occasionally domesticated for the host physiology. In addition, HERV transcriptional modulation is of great interest to clarify the etiology of complex disorders such as cancer, even if a few studies assessed the specific HERV loci modulated in tumor tissues. In the present work, we used a transcriptomic approach to investigate the specific expression of ~3300 HERV loci in paired tumor and normal tissues of 7 colorectal cancer (CRC) patients. A total of 102 HERVs were significantly modulated in CRC, with a general tendency towards downregulation. Of note, among the 42 upregulated HERVs 23 belonged to the HERV-H group, that is the most investigated in CRC. De novo transcriptome reconstruction and qPCR validation allowed to identify a transcript from a HERV-H locus on chromosome Xp22.3 with high specific expression in CRC samples, potentially encoding for a partial Pol protein. These results provide a detailed description of HERV transcriptional variations in CRC and its interindividual variability, identifying a HERV-H transcript that deserves further investigation for its possible impact on tumor progression.