scholarly journals Antiviral activity of a human placental protein of retroviral origin

2020 ◽  
Author(s):  
John A. Frank ◽  
Manvendra Singh ◽  
Harrison B. Cullen ◽  
Raphael A. Kirou ◽  
Carolyn B. Coyne ◽  
...  
Keyword(s):  
Cell Culture ◽  
Antiviral Activity ◽  
Cell Receptor ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Zoonotic Infections ◽  
Type D ◽  
Transcriptomics Data ◽  
Placental Protein ◽  
Necessary And Sufficient

SummaryViruses circulating in wild and domestic animals pose a constant threat to human health1. Identifying human genetic factors that protect against zoonotic infections is a health priority. The RD-114 and Type-D retrovirus (RDR) interference group includes infectious viruses that circulate in domestic cats and various Old World monkeys (OWM), and utilize ASCT2 as a common target cell receptor2. While human ASCT2 can mediate RDR infection in cell culture, it is unknown whether humans and other hominoids encode factors that restrict RDR infection in nature2,3. Here we test the hypothesis that Suppressyn, a truncated envelope protein that binds ASCT2 and is derived from a human endogenous retrovirus4,5, restricts RDR infection. Transcriptomics and regulatory genomics reveal that Suppressyn expression initiates in the preimplantation embryo. Loss and gain of function experiments in cell culture show Suppressyn expression is necessary and sufficient to restrict RDR infection. Evolutionary analyses show Suppressyn was acquired in the genome of a common ancestor of hominoids and OWMs, but preserved by natural selection only in hominoids. Restriction assays using modern primate orthologs and reconstructed ancestral genes indicate that Suppressyn antiviral activity has been conserved in hominoids, but lost in most OWM. Thus in humans and other hominoids, Suppressyn acts as a restriction factor against retroviruses with zoonotic capacity. Transcriptomics data predict that other virus-derived proteins with potential antiviral activity lay hidden in the human genome.

scholarly journals The HERV-K Human Endogenous Retrovirus Envelope Protein Antagonizes Tetherin Antiviral Activity

2014 ◽  
Vol 88 (23) ◽  
pp. 13626-13637 ◽  
Author(s):  
C. Lemaitre ◽  
F. Harper ◽  
G. Pierron ◽  
T. Heidmann ◽  
M. Dewannieux
Keyword(s):  
Antiviral Activity ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus

scholarly journals An Envelope Glycoprotein of the Human Endogenous Retrovirus HERV-W Is Expressed in the Human Placenta and Fuses Cells Expressing the Type D Mammalian Retrovirus Receptor

2000 ◽  
Vol 74 (7) ◽  
pp. 3321-3329 ◽  
Author(s):  
Jean-Luc Blond ◽  
Dimitri Lavillette ◽  
Valérie Cheynet ◽  
Olivier Bouton ◽  
Guy Oriol ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Expression Vector ◽  
Physiological Role ◽  
Endogenous Retrovirus ◽  
Open Reading Frame ◽  
Human Endogenous Retrovirus ◽  
Membrane Glycoprotein ◽  
Reading Frame ◽  
Herv Family ◽  
Type D

ABSTRACT A new human endogenous retrovirus (HERV) family, termed HERV-W, was recently described (J.-L. Blond, F. Besème, L. Duret, O. Bouton, F. Bedin, H. Perron, B. Mandrand, and F. Mallet, J. Virol. 73:1175–1185, 1999). HERV-W mRNAs were found to be specifically expressed in placenta cells, and an env cDNA containing a complete open reading frame was recovered. In cell-cell fusion assays, we demonstrate here that the product of the HERV-W env gene is a highly fusogenic membrane glycoprotein. Transfection of an HERV-W Env expression vector in a panel of cell lines derived from different species resulted in formation of syncytia in primate and pig cells upon interaction with the type D mammalian retrovirus receptor. Moreover, envelope glycoproteins encoded by HERV-W were specifically detected in placenta cells, suggesting that they may play a physiological role during pregnancy and placenta formation.

scholarly journals Human endogenous retrovirus transcription profiles of the kidney and kidney-derived cell lines

2011 ◽  
Vol 92 (10) ◽  
pp. 2356-2366 ◽  
Author(s):  
Sonja Haupt ◽  
Michele Tisdale ◽  
Michelle Vincendeau ◽  
Mary Anne Clements ◽  
David T. Gauthier ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cell Line ◽  
Cell Lines ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Tissue Samples ◽  
Transcription Pattern

The human genome comprises approximately 8–9 % of human endogenous retroviruses (HERVs) that are transcribed with tissue specificity. However, relatively few organs have been examined in detail for individual differences in HERV transcription pattern, nor have tissue-to-cell culture comparisons been frequently performed. Using an HERV-specific DNA microarray, a core HERV transcription profile was established for the human kidney comparing 10 tissue samples. This core represents HERV groups expressed uniformly or nearly so in non-tumour kidney tissue. The profiles obtained from non-tumour tissues were compared to 10 renal tumour tissues (renal cell carcinoma, RCC) derived from the same individuals and additionally, to 22 RCC cell lines. No RCC cell line or tumour-specific differences were observed, suggesting that HERV transcription is not altered in RCC. However, when comparing tissue transcription to cell line transcription, there were consistent differences. The differences were irrespective of cancer state and included cell lines derived from non-tumour kidney tissue, suggesting that a specific alteration of HERV transcription occurs when establishing cell lines. In contrast to previous publications, all known HERV-derived tumour antigens, including those identified in RCC, were expressed both in multiple RCC cell lines and several non-tumour tissue-derived cell lines, a result that contrasts with findings from patient samples. The results establish the core kidney transcription pattern of HERVs and reveal differences between cell culture lines and tissue samples.

scholarly journals Functional Analysis of the env Open Reading Frame in Human Endogenous Retrovirus IDDMK1,222 Encoding Superantigen Activity

2000 ◽  
Vol 74 (14) ◽  
pp. 6386-6393 ◽  
Author(s):  
Matthias Lapatschek ◽  
Susanne Dürr ◽  
Roswitha Löwer ◽  
Christine Magin ◽  
Hermann Wagner ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell Lymphoma ◽  
Cell Receptor ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Expression Vectors ◽  
Human Endogenous Retrovirus ◽  
Human Major Histocompatibility Complex ◽  
Reading Frame

ABSTRACT Mice harbor a family of endogenous retroviruses, the mouse mammary tumor viruses (MMTV), which encode superantigens. These superantigens are responsible for the deletion of T cells expressing certain Vβ chains of the T-cell receptor in the thymus. Human T cells are able to recognize MMTV-encoded superantigens presented by human major histocompatibility complex class II-positive cells. Owing to this and to the similarity of the human and murine immune systems, it was speculated that human endogenous retroviruses might also code for superantigens. Recently, it was reported that a proviral clone (IDDMK1,222) of the human endogenous retrovirus family HTDV/HERV-K encodes a superantigen. The putative superantigen gene was located within the env region of the virus. Stimulated by these findings, we amplified by PCR and cloned into eucaryotic expression vectors open reading frames (ORFs) which were identical or very similar to IDDMK1,222. When we transfected these vectors into A20 cells, a murine B-cell lymphoma, we were able to demonstrate mRNA expression and protein production. However, we did not find any evidence that the ORF stimulated human or murine T cells in a Vβ-specific fashion, the most prominent feature of superantigens.

scholarly journals Influence of different glycoproteins and of the virion core on SERINC5 antiviral activity

2019 ◽  
Author(s):  
William E. Diehl ◽  
Mehmet H. Guney ◽  
Pyae Phyo Kyawe ◽  
Judith M. White ◽  
Massimo Pizzato ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Antiviral Activity ◽  
Viral Entry ◽  
Ebola Virus ◽  
Endogenous Retrovirus ◽  
Marburg Virus ◽  
Human Endogenous Retrovirus ◽  
Target Cells ◽  
Viral Glycoprotein ◽  
Hiv 1

ABSTRACTHost plasma membrane protein SERINC5 is incorporated into budding retrovirus particles where it blocks subsequent entry into susceptible target cells. Three accessory proteins encoded by diverse retroviruses, HIV-1 Nef, EIAV S2, and MLV Glycogag, each independently disrupt SERINC5 antiviral activity, by redirecting SERINC5 from the site of virion assembly on the plasma membrane to an internal RAB7+ endosomal compartment. Pseudotyping retroviruses with particular glycoproteins, e.g., the vesicular stomatitis glycoprotein (VSV G), renders the infectivity of particles resistant to inhibition by virion-associated SERINC5. To better understand viral determinants for SERINC5-sensitivity, the effect of SERINC5 was assessed using HIV-1, MLV, and M-PMV virion cores, pseudotyped with glycoproteins from Arenavirus, Coronavirus, Filovirus, Rhabdovirus, Paramyxovirus, and Orthomyxovirus genera. Infectivity of particles, pseudotyped with HIV-1, amphotropic-MLV, or influenza virus glycoproteins, was decreased by SERINC5, whether the core was provided by HIV-1, MLV, or M-PMV. Particles generated by all three cores, and pseudotyped with glycoproteins from either avian leukosis virus-A, human endogenous retrovirus K (HERV-K), ecotropic-MLV, HTLV-1, Measles morbillivirus, lymphocytic choriomeningitis mammarenavirus (LCMV), Marburg virus, Ebola virus, severe acute respiratory syndrome-related coronavirus (SARS-CoV), or VSV, were insensitive to SERINC5. In contrast, particles pseudotyped with M-PMV, RD114, or rabies virus (RABV) glycoproteins were sensitive to SERINC5, but only with particular retroviral cores. Resistance to SERINC5 by particular glycoproteins did not correlate with reduced SERINC5 incorporation into particles or with the route of viral entry. These findings indicate that some non-retroviruses may be sensitive to SERINC5 and that, in addition to the viral glycoprotein, the retroviral core influences sensitivity to SERINC5.IMPORTANCEThe importance of SERINC5 for inhibition of retroviruses is underscored by convergent evolution among three non-monophyletic retroviruses, each of which encodes a structurally unrelated SERINC5 inhibitor. One of these retroviruses causes tumors in mice, a second anemia in horses, and a third causes AIDS. SERINC5 is incorporated into retrovirus particles where it blocks entry into target cells, via a mechanism that is dependent on the viral glycoprotein. Here we demonstrate that retroviruses pseudotyped with glycoproteins from several non-retroviruses are also inhibited by SERINC5, suggesting that enveloped viruses other than retroviruses may also be inhibited by SERINC5. Additionally, we found that sensitivity to SERINC5 is determined by the retrovirus core, as well as by the glycoprotein. By better understanding how SERINC5 inhibits viruses we hope to extend fundamental understanding of virus replication and of the native role of SERINC5 in cells, and perhaps to advance the development of new antiviral strategies.

Evidence for a functional subclass of the RTVL-H family of human endogenous retrovirus-like sequences.

1993 ◽  
Vol 67 (6) ◽  
pp. 2981-2989 ◽  
Author(s):  
D A Wilkinson ◽  
N L Goodchild ◽  
T M Saxton ◽  
S Wood ◽  
D L Mager
Keyword(s):  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus

Association of HERV-K and LINE-1 hypomethylation with reduced disease-free survival in melanoma patients

Epigenomics ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 1689-1706
Author(s):  
Maurizio Cardelli ◽  
Remco van Doorn ◽  
Lares Larcher ◽  
Michela Di Donato ◽  
Francesco Piacenza ◽  
...  
Keyword(s):  
Independent Predictor ◽  
Disease Free Survival ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Free Survival ◽  
Melanocytic Lesions ◽  
Long Interspersed Nuclear Elements ◽  
Melanoma Patients ◽  
And Gender ◽  
Disease Free

Aim: To evaluate CpG methylation of long interspersed nuclear elements 1 (LINE-1) and human endogenous retrovirus K (HERV-K) retroelements as potential prognostic biomarkers in cutaneous melanoma. Materials & methods: Methylation of HERV-K and LINE-1 retroelements was assessed in resected melanoma tissues from 82 patients ranging in age from 14 to 88 years. In addition, nevi from eight patients were included for comparison with nonmalignant melanocytic lesions. Results: Methylation levels were lower in melanomas than in nevi. HERV-K and LINE-1 methylation were decreased in melanoma patients with clinical parameters associated with adverse prognosis, while they were independent of age and gender. Hypomethylation of HERV-K (but not LINE-1) was an independent predictor of reduced disease-free survival. Conclusion: HERV-K hypomethylation can be a potential independent biomarker of melanoma recurrence.

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