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Grandi, N.

Publications and source records attributed to Grandi, N..

2 recordsLinked to original sources

Screening Envelope Genes Across Primate Genomes Reveals Evolution and Diversity Patterns of Endogenous Retroviruses

Endogenous Retroviruses (ERVs) are integrated into the host DNA as result of ancient germ line infections, majorly by now extinct exogenous retroviruses. Accordingly, vertebrates genomes contain thousands of ERV copies, providing "fossil" records for the ancestral retroviral diversity and its evolution within the host. Like exogenous retroviruses, ERV proviral sequence consists of gag, pro-pol, and env genes flanked by long terminal repeats (LTRs). In particular, the characterization of env gene changes over time allows both to understand ERVs evolutionary trajectory and to infer their potential role in host physiology, including their pathological involvement. Despite their potential impact on the host, a detailed characterization has been performed for few domesticated env genes, while a comprehensive survey of their abundance and diversity among primates genomes is still lacking. The study primarily focused on ERVs env that are known to be present in hominoid species, given their well-characterized nature and availability in public databases. Hence using these env sequences, we reconstructed 32 Env sequences representing the prototypes of these ancestral proteins in Class I, Class II, and Class III HERVs. These reconstructed Envs were then used for similarity search, phylogenetic analysis, and examination of recombination events occurred within primates genomes that were applied to 55 primate species across the Catarrhini and Platyrrhini parvorders. Through such comprehensive pipeline, we reconstituted a phylogenetic distribution of ERV based specifically on the env genes, showing that the ERVs have been prevalent and widely distributed across the primate lineage. We observed for the first time the presence of the HML (human mouse mammary tumor virus-like) group in the Platyrrhini parvorder, indicating initiation of spread of HML supergroup before the split between New World Monkeys (NWM) and Old World Monkeys (OWM) i.e. even before 40 mya. Importantly, we confirmed interclass and intra-class env recombination events confirming the phenomenon of "env snatching" among primates ERVs. As a result, we demonstrate that tracing the diversity patterns of ERVs env provides relevant insights into the retroviral evolutionary history of ERVs in Catarrhini and Platyrrhini parvorders. Overall, our findings reveal that env recombination contributes to the diversification of ERVs, thereby broadening our comprehension of retroviral and primate evolution.

microbiology↗

RNA-seq transcriptome analysis reveals LTR-retrotransposons modulation in Human Peripheral Blood Mononuclear Cells (PBMCs) after in vivo Lipopolysaccharides (LPS) injection

Human Endogenous Retroviruses (HERVs) and Mammalian apparent LTR-retrotransposons (MaLRs) are retroviral sequences that integrated into the germline cells millions year ago. Transcripts of these LTR-retrotransposons are present in several tissues, and their expression is modulated in pathological conditions, although their function remains often far from being understood. In this work, we focused on the HERVs/MaLRs expression and modulation in a scenario of immune system activation. We used a public dataset of Human Peripheral Blood Mononuclear Cells (PBMCs) RNA-seq from 15 healthy participants to a clinical trial before and after the exposure to Lipopolysaccharide (LPS), for which we established an RNA-seq workflow for the identification of expressed and modulated cellular genes and LTR-retrotransposon elements. ImportanceWe described the HERV and MaLR transcriptome in PBMCs, finding that about 8.4 % of the LTR-retrotransposons loci were expressed, and identifying the betaretrovirus-like HERVs as those with the highest percentage of expressed loci. We found 4,607 HERVs and MaLRs loci that were modulated as a result of in vivo stimulation with LPS. The HERV-H group showed the highest number of differentially expressed most intact proviruses. We characterized the HERV and MaLR loci differentially expressed checking their genomic context of insertion and, interestingly, we found a general co-localization with genes that are involved and modulated in the immune response, as consequence of LPS stimulation. The analyses of HERVs and MaLRs expression and modulation show that this LTR-retrotransposons are expressed in PBMCs and regulated in inflammatory settings. The similar regulation of HERVs/MaLRs and genes after LPS stimulation suggests possible interactions of LTR-retrotransposons and the immune host response.

microbiology↗