Infection by Diverse HIV-1 Subtypes Leads to Different Elevations in HERV-K Transcriptional Levels in Human T Cell Lines

Li, Xi; Guo, Yaolin; Li, Hanping; Huang, Xiaofeng; Pei, Zhichao; Wang, Xiaolin; Liu, Yongjian; Jia, Lei; Li, Tianyi; Bao, Zhenmin; Wang, Xiaorui; Han, Leilei; Han, Jingwan; Li, Jingyun

doi:10.3389/fmicb.2021.662573

Cited by 13 publications

(15 citation statements)

References 64 publications

(101 reference statements)

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“…Surprisingly we were unable to reveal an impact of either HIV-1 or HIV-2 infection in HERV expression in CD4SP thymocytes using both CCR5-and CXCR4-tropic primary isolates. Although we did not exclude a possible later up-regulation of HERV expression, these results suggest a wired control of their expression in these mature quiescent thymocytes, in contrast with peripheral and activated CD4 T cells (18,20,35).…”

Section: Discussioncontrasting

confidence: 57%

“…Recent data from several cell types and tissues have also been highlighting host restriction factors that limit HERV expression (9), and the interplay with other viruses, including HIV and SARS-CoV-2 (7,(18)(19)(20)(21)(22). It is likely that the interplay between HERV expression and the activation of the cell-intrinsic pathways that detect cytoplasmic DNA and/or RNA may play a role in the response to viral infections, as well as in the human thymus, including possible modulation during cell selection (10).…”

Section: Introductionmentioning

confidence: 99%

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Expression of Human Endogenous Retroviruses in the Human Thymus Along T Cell Development

et al. 2022

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Human Endogenous Retroviruses (HERVs) constitute up to 8% of the human genome and have been emerging as important modulators of the immune system, being associated with cancer, autoimmunity and infectious diseases. Here, we investigated the expression of three HERV families in the human thymus. HERV-K, -W, and -R envelope (env) and HERV-K gag transcriptional levels were quantified in the main thymocyte subsets, thymic epithelial cells (TECs), B cells and myeloid populations, and Env protein expression was studied in thymic tissue. We found that HERV mRNA decreased with T cell development, which was in agreement with the identification of HERV-K Env protein in CD3 negative cortical cells. These results suggest a distinct regulation of HERV expression along T cell development, prompting us to evaluate the interplay with host restriction factors and potential underlying pathways. The transcriptional levels of some HERVs were found to positively correlate with the expression of the host restriction factors APOBEC3G and SLFN11, and, conversely, a negative correlation was found with SAMHD1. Moreover, IFN-α and IFN-γ induced the upregulation of HERV-K env and gag in purified CD4 single-positive thymocytes. Additionally, we found high levels of HERV mRNAs in TECs. Overall, our data support a tight regulation of HERV expression during human T cell development, with possible implications for the process of T cell selection.

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Section: Discussioncontrasting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Expression of Human Endogenous Retroviruses in the Human Thymus Along T Cell Development

et al. 2022

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“…Significantly high expressions of the HERV-K (HML-2) gag , env , and pol genes were detected in both moderate and severe COVID-19 patients. The gene expression of HERV-K (HML-2) is under the direct control of its long terminal repeats (LTRs), studies have shown that the HIV-1 tat gene can induce transcriptional activation of HERV-K(HML-2) LTR [ 65 , 66 , 67 ]. We speculate that the high expression of HERV-K (HML-2) gag , env , and pol genes in whole blood of COVID-19 patients may also be due to the similar activation of some specific SARS-CoV-2 genes, which increase the expression of the LTR region.…”

Section: Discussionmentioning

confidence: 99%

High Expression of HERV-K (HML-2) Might Stimulate Interferon in COVID-19 Patients

Guo

Yang

Liu

et al. 2022

Viruses

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Background. Interferon is a marker of host antiviral immunity, which is disordered in COVID-19 patients. ERV can affect the secretion of interferon through the cGAS-STING pathway. In this study, we explored whether IFN-I and HERV-K (HML-2) were activated in COVID-19 patients and whether there was an interaction between them. Methods. We collected blood samples from COVID-19 patients and healthy controls. We first detected the expression of HERV-K (HML-2) gag, env, and pol genes and IFN-I-related genes between patients and healthy people by qPCR, synchronously detected VERO cells infected with SARS-CoV-2. Then, the chromosome distributions of highly expressed HERV-K (HML-2) gag, env, and pol genes were mapped by the next-generation sequencing results, and GO analysis was performed on the related genes. Results. We found that the HERV-K (HML-2) gag, env, and pol genes were highly expressed in COVID-19 patients and VERO cells infected with SARS-CoV-2. The interferon-related genes IFNB1, ISG15, and IFIT1 were also activated in COVID-19 patients, and GO analysis showed that HERV-K (HML-2) can regulate the secretion of interferon. Conclusions. The high expression of HERV-K (HML-2) might activate the increase of interferon in COVID-19 patients, proving that HERV-K does not only play a negative role in the human body.

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“…For each amplicon, cDNA samples were measured in triplicate. Primer sequences for amplification of HERV-K (HML-2) gag , pol , and env and β-actin were obtained from a previous study ( Li et al, 2021 ). These sequences were checked by the Primer Blast, Oligocalc, and Gene Runner programs.…”

Section: Methodsmentioning

confidence: 99%

“…The probe sets HERV-K (HML-2) env -C1, HERV-K (HML-2) pol -C2, or HERV-K (HML-2) gag -C3 (Advanced Cell Diagnostics, United States) consisted of 20 dual probes targeting different segments within the HERV-K (HML-2) env , HERV-K (HML-2) pol , or HERV-K (HML-2) gag . The standard sample was pretreated according to the manufacturer’s instructions and the previously reported literature ( Wang et al, 2012 ; Li et al, 2021 ). After the cells were treated, they were inoculated on culture slides.…”

Section: Methodsmentioning

confidence: 99%

Significant Upregulation of HERV-K (HML-2) Transcription Levels in Human Lung Cancer and Cancer Cells

Yang

Guo

et al. 2022

Front. Microbiol.

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Lung cancer is the second most common cancer worldwide and the leading cause of cancer death in the world. Therefore, there is an urgent need to develop new and effective biomarkers for diagnosis and treatment. Under this circumstance, human endogenous retroviruses (HERVs) were recently introduced as novel biomarkers for cancer diagnosis. This study focused on the correlation between lung cancer and HERV-K (HML-2) transcription levels. At the cellular level, different types of lung cancer cells and human normal lung epithelial cells were used to analyze the transcription levels of the HERV-K (HML-2) gag, pol, and env genes by RT–qPCR. At the level of lung cancer patients, blood samples with background information from 734 lung cancer patients and 96 healthy persons were collected to analyze the transcription levels of HERV-K (HML-2) gag, pol, and env genes. The results showed that the transcriptional levels of the HERV-K (HML-2) gag, pol, and env genes in lung cancer cells and lung cancer patient blood samples were significantly higher than those in the healthy controls, which was also verified by RNAScope ISH technology. In addition, we also found that there was a correlation between the abnormal transcription levels of HERV-K (HML-2) genes in lung cancer patients and the clinicopathological parameters of lung cancer. We also identified the distribution locations of the gag, pol, and env primer sequences on each chromosome and analyzed the function of these loci. In conclusion, HERV-K (HML-2) genes may be a potential biomarker for the diagnosis of lung cancer.

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Infection by Diverse HIV-1 Subtypes Leads to Different Elevations in HERV-K Transcriptional Levels in Human T Cell Lines

Cited by 13 publications

References 64 publications

Expression of Human Endogenous Retroviruses in the Human Thymus Along T Cell Development

Expression of Human Endogenous Retroviruses in the Human Thymus Along T Cell Development

High Expression of HERV-K (HML-2) Might Stimulate Interferon in COVID-19 Patients

Significant Upregulation of HERV-K (HML-2) Transcription Levels in Human Lung Cancer and Cancer Cells

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