{
  "abstract": "Background Human endogenous retroviruses (HERVs) are the result of an ancient retroviral integration in the human germline and currently represent around 8% of the human genome. HERV transcription may be tissue-specific and has been correlated with inflammation and tumors. Among HERVs, the HERV-K family is made up of 10 groups (HML-1 to HML-10). Various interactions have been described between HIV and HERVs, mostly mediated by HIV tat protein. Aims of the study were to explore HERV-K transcription in peripheral blood mononuclear cells (PBMC) of acute and chronic HIV infections and their modifications after antiretroviral treatment (ART).Materials and Methods To identify HML-2 and HLM-6 transcripts, single-cell transcriptomics was carried out on PBMCs collected from 1 acute naïve to antiretrovirals HIV-infection (S1) and 1 chronic on ART HIV-infection (S2). Single-cell RNA sequencing was performed with 10x Chromium technology and Illumina NovaSeq sequencing. Bioinformatic analysis was performed using Cell Ranger together with an ad hoc established bioinformatic pipeline. Cell Typist fine annotation was used to assign cell type to the identified cell clusters. Expression levels of HLM-6 env were established in plasma samples by Real-time PCR, comparing them with the beta-actin gene levels, in 7 acute/recent infections (AHI) and in 7 chronic infections (CHI), at the moment of serodiagnosis (T0) and after 1 year of ART (T1), when HIV-1 RNA levels were < 50 copies/ml in all subjects. Five plasma samples from healthy donors (HD) were used as controls. Statistical evaluation was performed using Mann-Whitney test and Benjamini-Hochberg FDR correction.Results LTR, gag, and env transcripts of HML-2 and HML-6 were found in PBMC from both S1 and S2 subjects. In figure 1, cell clusters showing HLM-6 transcript expression in S2 PBMC (A) and the cell-type annotation (B) are shown. From a total of 2,646 identified cells, HML-6 transcripts were significantly more expressed (% of cells of a given cell type expressing HML-6 transcripts) in non-classical monocytes (18.4%), CD4 T cm/naïve (14.1%), and CD8 Tem/Temra (11.3%). At T0, HIV-1 viremia did not differ between AHI and CHI: 6.08 (4.68-7.74) and 5.66 (4.28-6.45) Log copies/ml. HML-6 transcripts were not detected in any HD, and they were tendentially higher in CHI than in AHI, at both T0 5.29 (3.38-6.18) vs 6.69 (4.11-12.4) and T1 8.03 (6.33-8.97) vs 13.4 (13.221-14.17), median (IRQ) ΔCt between env HML-6 and beta-actin. ART was able to significantly reduce HLM-6 env expression in both AHI (p=0.031) and CHI (p=0.016).Conclusions HERV transcripts may be found in PWH in both acute and chronic infections, with higher expression of HML-6 compared to HLM-2. Non-classical monocytes, CD4 Tcm/naïve, and CD8 Tem/Temra are the main cellular types containing HML-6 transcripts. Endogenous retrovirus expression may be successfully reduced by ART, irrespective of whether it is initiated in acute or chronic infection.Abstract P236 Figure 1Cell cluster and HLM-6 transcripts visualization. (A) uniform manifold approximation and projection (UMAP) of HLM-6 cumulative expression in S2 PBMC. A gradient from gray to red is used to highlight HLM-6 transcripts expression levels within cells. (B) UMAP of different cluster, identified with cell typist fine annotation, of S2 PBMC. Several colours, displayed in the legend on the right, are used to highlight each cellular cluster",
  "authors": [
    {
      "affiliations": [
        "INMI L. Spallanzani, IRCCS, Rome, Italy"
      ],
      "name": "E Lazzari"
    },
    {
      "affiliations": [
        "University of Tuscia, Viterbo, Italy"
      ],
      "name": "D Pietrucci"
    },
    {
      "affiliations": [
        "INMI L. Spallanzani, IRCCS, Rome, Italy"
      ],
      "name": "G Rozera"
    },
    {
      "affiliations": [
        "INMI L. Spallanzani, IRCCS, Rome, Italy"
      ],
      "name": "L Fabeni"
    },
    {
      "affiliations": [
        "INMI L. Spallanzani, IRCCS, Rome, Italy"
      ],
      "name": "F Smoquina"
    },
    {
      "affiliations": [
        "INMI L. Spallanzani, IRCCS, Rome, Italy"
      ],
      "name": "G Berno"
    },
    {
      "affiliations": [
        "INMI L. Spallanzani, IRCCS, Rome, Italy"
      ],
      "name": "F Forbici"
    },
    {
      "affiliations": [
        "INMI L. Spallanzani, IRCCS, Rome, Italy"
      ],
      "name": "V Mazzotta"
    },
    {
      "affiliations": [
        "INMI L. Spallanzani, IRCCS, Rome, Italy"
      ],
      "name": "A Antinori"
    },
    {
      "affiliations": [
        "INMI L. Spallanzani, IRCCS, Rome, Italy",
        "University of Rome ‘Tor Vergata’, Rome, Italy"
      ],
      "name": "G Chillemi"
    },
    {
      "affiliations": [
        "INMI L. Spallanzani, IRCCS, Rome, Italy"
      ],
      "name": "F Maggi"
    },
    {
      "affiliations": [
        "INMI L. Spallanzani, IRCCS, Rome, Italy"
      ],
      "name": "I Abbate"
    }
  ],
  "title": "P236 Human endogenous retrovirus expression in peripheral blood of people with HIV in different phases of the infection and during antiretroviral treatment",
  "uid": "2c3af56b-5922-57d3-ae29-aa6100329c96"
}