scholarly journals Endogenous Retrovirus-Derived lnc-ALVE1-AS1 Exerts Antiviral Defense Against ALV-J Infection in Chicken Macrophages

2021 ◽  
Author(s):  
Huan Luo ◽  
Xuming Hu ◽  
Huixian Wu ◽  
Gul Zaib ◽  
Wenxian Chai ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Type I Interferons ◽  
Type I ◽  
Antiviral Defense ◽  
Antiviral Innate Immunity ◽  
Retroviral Infections ◽  
Avian Leukosis Virus Subgroup ◽  
Chicken Embryo Fibroblasts

Abstract Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections dating back many millions of years, and their derived transcripts with viral signatures are important sources of long noncoding RNAs (lncRNAs). We have previously shown that the chicken ERV-derived lncRNA lnc-ALVE1-AS1 exerts antiviral innate immunity in chicken embryo fibroblasts. However, it is not clear whether this endogenous retroviral RNA has a similar function in immune cells. Here, we found that lnc-ALVE1-AS1 was persistently inhibited in chicken macrophages after avian leukosis virus subgroup J (ALV-J) infection. Furthermore, overexpression of lnc-ALVE1-AS1 significantly inhibited the proliferation of exogenous ALV-J, whereas knockdown of lnc-ALVE1-AS1 promoted the proliferation of ALV-J in chicken macrophages. This phenomenon is attributed to the induction of antiviral innate immunity by lnc-ALVE1-AS1 in macrophages, whereas knockdown of lnc-ALVE1-AS1 had the opposite effect. Mechanistically, lnc-ALVE1-AS1 can be sensed by the cytosolic pattern recognition receptor TLR3 and trigger the type I interferons response. The present study provides novel insights into the antiviral defense of ERV-derived lncRNAs in macrophages and offers new strategies for future antiviral solutions.

scholarly journals When human guanylate-binding proteins meet viral infections

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Rongzhao Zhang ◽  
Zhixin Li ◽  
Yan-Dong Tang ◽  
Chenhe Su ◽  
Chunfu Zheng
Keyword(s):  
Innate Immunity ◽  
Viral Infection ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Downstream Signaling ◽  
Antiviral Innate Immunity

AbstractInnate immunity is the first line of host defense against viral infection. After invading into the cells, pathogen-associated-molecular-patterns derived from viruses are recognized by pattern recognition receptors to activate the downstream signaling pathways to induce the production of type I interferons (IFN-I) and inflammatory cytokines, which play critical functions in the host antiviral innate immune responses. Guanylate-binding proteins (GBPs) are IFN-inducible antiviral effectors belonging to the guanosine triphosphatases family. In addition to exerting direct antiviral functions against certain viruses, a few GBPs also exhibit regulatory roles on the host antiviral innate immunity. However, our understanding of the underlying molecular mechanisms of GBPs' roles in viral infection and host antiviral innate immune signaling is still very limited. Therefore, here we present an updated overview of the functions of GBPs during viral infection and in antiviral innate immunity, and highlight discrepancies in reported findings and current challenges for future studies, which will advance our understanding of the functions of GBPs and provide a scientific and theoretical basis for the regulation of antiviral innate immunity.

scholarly journals Noncanonical NF-κB Pathway Controls the Production of Type I Interferons in Antiviral Innate Immunity

Immunity ◽  
2014 ◽  
Vol 40 (3) ◽  
pp. 342-354 ◽  
Author(s):  
Jin Jin ◽  
Hongbo Hu ◽  
Haiyan S. Li ◽  
Jiayi Yu ◽  
Yichuan Xiao ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Type I Interferons ◽  
Type I ◽  
Antiviral Innate Immunity

scholarly journals Single-nucleotide methylation specifically represses type I interferon in antiviral innate immunity

2021 ◽  
Vol 218 (3) ◽  
Author(s):  
Zheng-jun Gao ◽  
Wen-ping Li ◽  
Xin-tao Mao ◽  
Tao Huang ◽  
Hao-li Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Innate Immunity ◽  
Viral Infections ◽  
Critical Role ◽  
Endogenous Retrovirus ◽  
Type I ◽  
Single Nucleotide ◽  
Antiviral Immune Response ◽  
Genome Bisulfite Sequencing ◽  
Antiviral Innate Immunity

Frequent outbreaks of viruses have caused a serious threat to public health. Previous evidence has revealed that DNA methylation is correlated with viral infections, but its role in innate immunity remains poorly investigated. Additionally, DNA methylation inhibitors promote IFN-I by upregulating endogenous retrovirus; however, studies of intrinsically demethylated tumors do not support this conclusion. This study found that Uhrf1 deficiency in myeloid cells significantly upregulated Ifnb expression, increasing resistance to viral infection. We performed whole-genome bisulfite sequencing and found that a single-nucleotide methylation site in the Ifnb promoter region disrupted IRF3 recruitment. We used site-specific mutant knock-in mice and a region-specific demethylation tool to confirm that this methylated site plays a critical role in regulating Ifnb expression and antiviral responses. These findings provide essential insight into DNA methylation in the regulation of the innate antiviral immune response.

scholarly journals Mobilization of Endogenous Retroviruses in Mice after Infection with an Exogenous Retrovirus

2008 ◽  
Vol 83 (6) ◽  
pp. 2429-2435 ◽  
Author(s):  
Leonard H. Evans ◽  
A. S. M. Alamgir ◽  
Nick Owens ◽  
Nick Weber ◽  
Kimmo Virtaneva ◽  
...  
Keyword(s):  
Germ Line ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Gene Sequences ◽  
Endogenous Viruses ◽  
Mammalian Genomes ◽  
Leukemia Viruses ◽  
Retroviral Infections ◽  
Ecotropic Virus ◽  
Rna Transcript

ABSTRACT Mammalian genomes harbor a large number of retroviral elements acquired as germ line insertions during evolution. Although many of the endogenous retroviruses are defective, several contain one or more intact viral genes that are expressed under certain physiological or pathological conditions. This is true of the endogenous polytropic retroviruses that generate recombinant polytropic murine leukemia viruses (MuLVs). In these recombinants the env gene sequences of exogenous ecotropic MuLVs are replaced with env gene sequences from an endogenous polytropic retrovirus. Although replication-competent endogenous polytropic retroviruses have not been observed, the recombinant polytropic viruses are capable of replicating in numerous species. Recombination occurs during reverse transcription of a virion RNA heterodimer comprised of an RNA transcript from an endogenous polytropic virus and an RNA transcript from an exogenous ecotropic MuLV RNA. It is possible that homodimers corresponding to two full-length endogenous RNA genomes are also packaged. Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections.

scholarly journals Route of Infection Determines the Impact of Type I Interferons on Innate Immunity to Listeria monocytogenes

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65007 ◽  
Author(s):  
Elisabeth Kernbauer ◽  
Verena Maier ◽  
Isabella Rauch ◽  
Mathias Müller ◽  
Thomas Decker
Keyword(s):  
Innate Immunity ◽  
Listeria Monocytogenes ◽  
Type I Interferons ◽  
Type I ◽  
Route Of Infection ◽  
The Impact

scholarly journals Toll-Like Receptors and their Contribution to Innate Immunity: Focus on TLR4 Activation by Lipopolysaccharide

2014 ◽  
Vol 4 (1) ◽  
pp. 1-23 ◽  
Author(s):  
Maciej Czerkies ◽  
Katarzyna Kwiatkowska
Keyword(s):  
Innate Immunity ◽  
Ligand Binding ◽  
Transmembrane Domain ◽  
Adaptor Proteins ◽  
Type I Interferons ◽  
Type I ◽  
Toll Like Receptors ◽  
Signalling Cascades ◽  
Genes Encoding ◽  
Membrane Components

Summary Mechanisms of innate immunity are triggered as a result of recognition of evolutionarily conserved structures of microorganisms, named pathogen-associated molecular patterns. Their recognition is mediated by specialized receptors which initiate signalling cascades leading to expression of pro-inflammatory mediators and regulation of acquired immunity. Among several classes of such receptors, Toll-like receptors (TLRs) are extensively studied as they can sense an array of microbial cell wall and membrane components as well as single- and double-stranded RNA and DNA motifs typical for microorganisms. Each TLR consists of a ligand-binding domain containing leucine-rich repeats, a single transmembrane domain and a signalling TIR domain. After ligand binding, TLRs dimerize which facilitates the interaction of their TIR domains with adaptor proteins triggering signalling cascades. TLRs engage four common adaptor proteins, about ten signalling kinases, and a few transcription factors including NFκB, IRF and AP-1. In this review, special attention is paid to TLR4 activated by lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, since an exaggerated response to LPS may lead to potentially deadly septic shock. In recent years considerable progress has been made in the understanding of how the cooperation of several proteins, including CD14, TLR4/MD-2 complex and scavenger receptors, modulates the cell response to LPS. These studies have also revealed a dichotomy of signalling pathways triggered by TLR4 which depends on the participation of MyD88 and TRIF adaptor proteins and leads to the expression of genes encoding pro-inflammatory cytokines and type I interferons, respectively. The key event in the TRIF-dependent pathway is the internalization of activated TLR4.

scholarly journals Hypermutation of an Ancient Human Retrovirus by APOBEC3G

2008 ◽  
Vol 82 (17) ◽  
pp. 8762-8770 ◽  
Author(s):  
Young Nam Lee ◽  
Michael H. Malim ◽  
Paul D. Bieniasz
Keyword(s):  
Human Genome ◽  
Cytidine Deaminase ◽  
Modern Human ◽  
Endogenous Retrovirus ◽  
Human Infection ◽  
Endogenous Retroviruses ◽  
Host Interactions ◽  
Apobec3 Proteins ◽  
Retroviral Infections

ABSTRACT Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome, but all are remnants of ancient retroviral infections and harbor inactivating mutations that render them replication defective. Nevertheless, as viral “fossils,” HERVs may provide insights into ancient retrovirus-host interactions and their evolution. Indeed, one endogenous retrovirus [HERV-K(HML-2)], which has replicated in humans for the past few million years but is now thought to be extinct, was recently reconstituted in a functional form, and infection assays based on it have been established. Here, we show that several human APOBEC3 proteins are intrinsically capable of mutating and inhibiting infection by HERV-K(HML-2) in cell culture. We also present striking evidence that two HERV-K(HML-2) proviruses that are fixed in the modern human genome (HERV-K60 and HERV-KI) were subjected to hypermutation by a cytidine deaminase. Inspection of the spectrum of mutations that are found in HERV-K proviruses in the human genome and HERV-K DNA generated during in vitro replication in the presence of each of the human APOBEC3 proteins unequivocally identifies APOBEC3G as the cytidine deaminase responsible for hypermutation of HERV-K60 and HERV-KI. This is a rare example of the antiretroviral effects of APOBEC3G in the setting of natural human infection, whose consequences have been fossilized in human DNA, and a striking example of inactivation of ancient retroviruses in humans through enzymatic cytidine deamination.

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