scholarly journals Comprehensive Analysis of HERV Transcriptome in HIV+ Cells: Absence of HML2 Activation and General Downregulation of Individual HERV Loci

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 481 ◽  
Author(s):  
Nicole Grandi ◽  
Maria Paola Pisano ◽  
Sante Scognamiglio ◽  
Eleonora Pessiu ◽  
Enzo Tramontano
Keyword(s):  
Hiv Infection ◽  
De Novo ◽  
Endogenous Retrovirus ◽  
Open Reading Frames ◽  
Human Endogenous Retrovirus ◽  
Bioinformatics Pipeline ◽  
Transcriptional Modulation ◽  
Herv Expression ◽  
Coding Potential ◽  
Hiv 1

Human endogenous retrovirus (HERV) expression is currently studied for its possible activation by HIV infection. In this context, the HERV-K(HML2) group is the most investigated: it has been proposed that HIV-1 infection can prompt HML2 transcription, and that HML2 proteins can affect HIV-1 replication, either complementing HIV or possibly influencing antiretroviral therapy. However, little information is available on the expression of other HERV groups in HIV infection. In the present study, we used a bioinformatics pipeline to investigate the transcriptional modulation of approximately 3250 well-characterized HERV loci, comparing their expression in a public RNA-seq profile, including a HIV-1-infected and a control T cell culture. In our pilot study, we found approximately 200 HERV loci belonging to 35 HERV groups that were expressed in one or both conditions, with transcripts per million (TPM) values from 1 to >500. Intriguingly, HML2 elements constituted only the 3% of expressed HERV loci, and in most cases (160) HERV expression was downregulated in the HIV-infected culture, showing from a 1- to 14-fold decrease as compared to uninfected cells. HERV transcriptome has been inferred de novo and employed to predict a total of about 950 HERV open reading frames (ORFs). These have been validated according to the coding potential and estimated abundance of the corresponding transcripts, leading to a set of 57 putative proteins potentially encoded by 23 HERV loci. Analysis showed that some individual loci have a coding potential that deserves further investigation. Among them, a HML6 provirus at locus 19q13.43 was predicted to produce a transcript showing the highest TPM among HERV-derived transcripts, being upregulated in HIV+ cells and inferred to produce Gag and Env puteins with possible biological activity.

scholarly journals Modulation of human endogenous retrovirus (HERV) transcription during persistent and de novo HIV-1 infection

Retrovirology ◽  
2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Michelle Vincendeau ◽  
Ingmar Göttesdorfer ◽  
Julia M H Schreml ◽  
Armand G Ngounou Wetie ◽  
Jens Mayer ◽  
...  
Keyword(s):  
De Novo ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Hiv 1

scholarly journals Human Endogenous Retrovirus Expression Is Inversely Associated with Chronic Immune Activation in HIV-1 Infection

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e41021 ◽  
Author(s):  
Christopher E. Ormsby ◽  
Devi SenGupta ◽  
Ravi Tandon ◽  
Steven G. Deeks ◽  
Jeffrey N. Martin ◽  
...  
Keyword(s):  
Immune Activation ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Chronic Immune Activation ◽  
Hiv 1

scholarly journals Membrane Binding and Subcellular Localization of Retroviral Gag Proteins Are Differentially Regulated by MA Interactions with Phosphatidylinositol-(4,5)-Bisphosphate and RNA

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Jingga Inlora ◽  
David R. Collins ◽  
Marc E. Trubin ◽  
Ji Yeon J. Chung ◽  
Akira Ono
Keyword(s):  
Virus Assembly ◽  
Membrane Binding ◽  
Endogenous Retrovirus ◽  
Single Amino Acid ◽  
Human Endogenous Retrovirus ◽  
Structural Protein ◽  
Acidic Phospholipid ◽  
Specific Localization ◽  
Hiv 1

ABSTRACTThe matrix (MA) domain of HIV-1 mediates proper Gag localization and membrane binding via interaction with a plasma-membrane (PM)-specific acidic phospholipid, phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]. HIV-1 MA also interacts with RNA, which prevents Gag from binding to membranes containing phosphatidylserine, a prevalent cellular acidic phospholipid. These results suggest that the MA-bound RNA promotes PM-specific localization of HIV-1 Gag by blocking nonspecific interactions with cellular membranes that do not contain PI(4,5)P2. To examine whether PI(4,5)P2dependence and RNA-mediated inhibition collectively determine MA phenotypes across a broad range of retroviruses and elucidate the significance of their interrelationships, we compared a panel of Gag-leucine zipper constructs (GagLZ) containing MA of different retroviruses. We found thatin vitromembrane binding of GagLZ via HIV-1 MA and Rous sarcoma virus (RSV) MA is both PI(4,5)P2dependent and susceptible to RNA-mediated inhibition. The PM-specific localization and virus-like particle (VLP) release of these GagLZ proteins are severely impaired by overexpression of a PI(4,5)P2-depleting enzyme, polyphosphoinositide 5-phosphatase IV (5ptaseIV). In contrast, membrane binding of GagLZ constructs that contain human T-lymphotropic virus type 1 (HTLV-1) MA, murine leukemia virus (MLV) MA, and human endogenous retrovirus K (HERV-K) MA is PI(4,5)P2independent and not blocked by RNA. The PM localization and VLP release of these GagLZ chimeras were much less sensitive to 5ptaseIV expression. Notably, single amino acid substitutions that confer a large basic patch rendered HTLV-1 MA susceptible to the RNA-mediated block, suggesting that RNA readily blocks MA containing a large basic patch, such as HIV-1 and RSV MA. Further analyses of these MA mutants suggest a possibility that HIV-1 and RSV MA acquired PI(4,5)P2dependence to alleviate the membrane binding block imposed by RNA.IMPORTANCEMA basic residues in the HIV-1 structural protein Gag interact with phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and RNA. RNA inhibits HIV-1 MA binding to non-PI(4,5)P2acidic lipids. This inhibition may promote PM specificity of Gag membrane binding, an early essential step in virus assembly. However, whether and how relationships between these interactions have developed among retroviruses are poorly understood. In this study, by comparing diverse retroviral MA domains, we elucidated a strong correlation among PI(4,5)P2dependence, susceptibility to RNA-mediated inhibition, and cellular behaviors of Gag. Mutagenesis analyses suggest that a large basic patch on MA is sufficient to confer susceptibility to RNA-mediated inhibition but not for PI(4,5)P2-dependent membrane binding. Our findings highlight RNA’s role as a general blocker of large basic patches and suggest a possibility that some retroviruses, including HIV-1, have evolved to bind PI(4,5)P2, while others have adopted smaller basic patches on their MA domains, to overcome the RNA-mediated restriction of membrane binding.

scholarly journals Human Endogenous Retrovirus Family HERV-K(HML-5): Status, Evolution, and Reconstruction of an Ancient Betaretrovirus in the Human Genome

2004 ◽  
Vol 78 (16) ◽  
pp. 8788-8798 ◽  
Author(s):  
Laurence Lavie ◽  
Patrik Medstrand ◽  
Werner Schempp ◽  
Eckart Meese ◽  
Jens Mayer
Keyword(s):  
Human Genome ◽  
Germ Line ◽  
Consensus Sequence ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Primer Binding Site ◽  
Human Endogenous Retrovirus ◽  
New World Primates ◽  
Human Endogenous Retroviruses

ABSTRACT The human genome harbors numerous distinct families of so-called human endogenous retroviruses (HERV) which are remnants of exogenous retroviruses that entered the germ line millions of years ago. We describe here the hitherto little-characterized betaretrovirus HERV-K(HML-5) family (named HERVK22 in Repbase) in greater detail. Out of 139 proviruses, only a few loci represent full-length proviruses, and many lack gag protease and/or env gene regions. We generated a consensus sequence from multiple alignment of 62 HML-5 loci that displays open reading frames for the four major retroviral proteins. Four HML-5 long terminal repeat (LTR) subfamilies were identified that are associated with monophyletic proviral bodies, implying different evolution of HML-5 LTRs and genes. Sequence analysis indicated that the proviruses formed approximately 55 million years ago. Accordingly, HML-5 proviral sequences were detected in Old World and New World primates but not in prosimians. No recent activity is associated with this HERV family. We also conclude that the HML-5 consensus sequence primer binding site is identical to methionine tRNA. Therefore, the family should be designated HERV-M. Our study provides important insights into the structure and evolution of the oldest betaretrovirus in the primate genome known to date.

scholarly journals HIV-1 Interacts with Human Endogenous Retrovirus K (HML-2) Envelopes Derived from Human Primary Lymphocytes

2014 ◽  
Vol 88 (11) ◽  
pp. 6213-6223 ◽  
Author(s):  
D. Brinzevich ◽  
G. R. Young ◽  
R. Sebra ◽  
J. Ayllon ◽  
S. M. Maio ◽  
...  
Keyword(s):  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Hiv 1

scholarly journals Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K

2000 ◽  
Vol 74 (20) ◽  
pp. 9353-9361 ◽  
Author(s):  
Hal P. Bogerd ◽  
Heather L. Wiegand ◽  
Jin Yang ◽  
Bryan R. Cullen
Keyword(s):  
Nuclear Export ◽  
Biological Activities ◽  
Endogenous Retrovirus ◽  
Viral Rna ◽  
Human Endogenous Retrovirus ◽  
Nuclear Rna ◽  
Rna Export ◽  
Nuclear Rna Export ◽  
Hiv 1 ◽  
Rev Protein

ABSTRACT Nuclear export of the incompletely spliced mRNAs encoded by several complex retroviruses, including human immunodeficiency virus type 1 (HIV-1), is dependent on a virally encoded adapter protein, termed Rev in HIV-1, that directly binds both to a cis-acting viral RNA target site and to the cellular Crm1 export factor. Human endogenous retrovirus K, a family of ancient endogenous retroviruses that is not related to the exogenous retrovirus HIV-1, was recently shown to also encode a Crm1-dependent nuclear RNA export factor, termed K-Rev. Although HIV-1 Rev and K-Rev display little sequence identity, they share the ability not only to bind to Crm1 and to RNA but also to form homomultimers and shuttle between nucleus and cytoplasm. We have used mutational analysis to identify sequences in the 105-amino-acid K-Rev protein required for each of these distinct biological activities. While mutations in K-Rev that inactivate any one of these properties also blocked K-Rev-dependent nuclear RNA export, several K-Rev mutants were comparable to wild type when assayed for any of these individual activities yet nevertheless defective for RNA export. Although several nonfunctional K-Rev mutants acted as dominant negative inhibitors of K-Rev-, but not HIV-1 Rev-, dependent RNA export, these were not defined by their inability to bind to Crm1, as is seen with HIV-1 Rev. In total, this analysis suggests a functional architecture for K-Rev that is similar to, but distinct from, that described for HIV-1 Rev and raises the possibility that viral RNA export mediated by the ∼25 million-year-old K-Rev protein may require an additional cellular cofactor that is not required for HIV-1 Rev function.

scholarly journals Determination of Sequences Required for Human Endogenous Retrovirus K Transduction and Its Recognition by Foreign Retroviral Virions

2015 ◽  
Vol 90 (6) ◽  
pp. 3243-3246
Author(s):  
Otto Erlwein ◽  
Nathan P. Sweeney ◽  
Raffaele de Leon ◽  
Gillian Wills ◽  
Mark J. Robinson ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Gene Therapy Vectors ◽  
Working Together ◽  
Hiv 1 ◽  
Murine Leukemia

Sequences necessary for transduction of human endogenous retrovirus (HERV)-Kcon, a consensus of the HERV-K(HML-2) family, were analyzed and found to reside in the leader/gagregion. They act in an orientation-dependent way and consist of at least two sites working together. Having defined these sequences, we exploited this information to produce a simple system to investigate to what extent virions of HERV-Kcon, murine leukemia virus, and HIV-1 have the ability to transduce each other's genomes, leading to potential contamination of gene therapy vectors.

scholarly journals Antibody to Human Endogenous Retrovirus Peptide in Urine of Human Immunodeficiency Virus Type 1-Positive Patients

1999 ◽  
Vol 6 (6) ◽  
pp. 783-786 ◽  
Author(s):  
Roy W. Stevens ◽  
Aldona L. Baltch ◽  
Raymond P. Smith ◽  
Bruce J. McCreedy ◽  
Phyllis B. Michelsen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Endogenous Retrovirus ◽  
Clinical State ◽  
Human Endogenous Retrovirus ◽  
Related Peptide ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human endogenous retrovirus (HERV)-like sequences are normal inherited elements that constitute several hundredths of the human genome. The expression of genes located within these elements can occur as a consequence of several different events, including persistent inflammation or genotoxic events. Antibodies to endogenous retroviral gene products have been found in a number of infectious, chronic, and malignant diseases, suggesting a role in disease initiation and progression. We studied human immunodeficiency virus type 1 (HIV-1)-infected patients for evidence of urine antibody to a HERV peptide and investigated correlates with clinical and laboratory parameters. Forty-three HIV-1-infected patients in documented asymptomatic, symptomatic, or AIDS stages of disease and 21 age- and gender-matched, uninfected controls were tested for antibody to HERV-related peptide 4.1. Urine specimens were examined in a blinded fashion with the Calypte Biomedical Corp. experimental enzyme immunoassay for antibody to peptide 4.1. Results were compared with demographic data, medical history, clinical state of disease, and results of other laboratory tests. Thirty-six percent of the asymptomatic (Centers for Disease Control and Prevention [CDC] category A) and 81.3% of both the symptomatic (CDC category B) and AIDS (CDC category C) patients were positive for antibody to HERV-related peptide 4.1. None of the controls were positive. In this study, antibodies to HERV-related peptide 4.1 were found more frequently in patients with advanced stages (categories B and C) of HIV-1 disease than in those patients with an earlier stage (category A) of HIV disease. In HIV patients, severe immunosuppression, defined as having had at least one opportunistic infection, correlated with the expression of antibody to a HERV-related peptide.

scholarly journals Molecular Characterization and Placental Expression of HERV-W, a New Human Endogenous Retrovirus Family

1999 ◽  
Vol 73 (2) ◽  
pp. 1175-1185 ◽  
Author(s):  
Jean-Luc Blond ◽  
Frédéric Besème ◽  
Laurent Duret ◽  
Olivier Bouton ◽  
Frédéric Bedin ◽  
...  
Keyword(s):  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Primer Binding Site ◽  
Human Endogenous Retrovirus ◽  
Cdna Clones ◽  
Human Endogenous Retroviruses ◽  
Herv Family ◽  
Flanking Sequences ◽  
Reading Frames

ABSTRACT The multiple sclerosis-associated retrovirus (MSRV) isolated from plasma of MS patients was found to be phylogenetically and experimentally related to human endogenous retroviruses (HERVs). To characterize the MSRV-related HERV family and to test the hypothesis of a replication-competent HERV, we have investigated the expression of MSRV-related sequences in healthy tissues. The expression of MSRV-related transcripts restricted to the placenta led to the isolation of overlapping cDNA clones from a cDNA library. These cDNAs spanned a 7.6-kb region containing gag, pol, and env genes; RU5 and U3R flanking sequences; a polypurine tract; and a primer binding site (PBS). As this PBS showed similarity to avian retrovirus PBSs used by tRNATrp, this new HERV family was named HERV-W. Several genomic elements were identified, one of them containing a complete HERV-W unit, spanning all cDNA clones. Elements of this multicopy family were not replication competent, asgag and pol open reading frames (ORFs) were interrupted by frameshifts and stop codons. A complete ORF putatively coding for an envelope protein was found both on the HERV-W DNA prototype and within an RU5-env-U3R polyadenylated cDNA clone. Placental expression of 8-, 3.1-, and 1.3-kb transcripts was observed, and a putative splicing strategy was described. The apparently tissue-restricted HERV-W long terminal repeat expression is discussed with respect to physiological and pathological contexts.

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