scholarly journals How Many Mammalian Reovirus Proteins are involved in the Control of the Interferon Response?

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 83 ◽  
Author(s):  
Delphine Lanoie ◽  
Simon Boudreault ◽  
Martin Bisaillon ◽  
Guy Lemay
Keyword(s):  
Immune Response ◽  
Host Cell ◽  
Innate Immune Response ◽  
Resistance Mechanisms ◽  
Innate Immune ◽  
Interferon Response ◽  
Gene Products ◽  
Interferon Signaling ◽  
Host Cell Response ◽  
Response Network

As with most viruses, mammalian reovirus can be recognized and attacked by the host-cell interferon response network. Similarly, many viruses have developed resistance mechanisms to counteract the host-cell response at different points of this response. Reflecting the complexity of the interferon signaling pathways as well as the resulting antiviral response, viruses can—and often have—evolved many determinants to interfere with this innate immune response and allow viral replication. In the last few years, it has been evidenced that mammalian reovirus encodes many different determinants that are involved in regulating the induction of the interferon response or in interfering with the action of interferon-stimulated gene products. In this brief review, we present our current understanding of the different reovirus proteins known to be involved, introduce their postulated modes of action, and raise current questions that may lead to further investigations.

RNA sensors as a mechanism of innate immune evasion among SARS-CoV2, HIV and Nipah viruses

2021 ◽  
Vol 22 ◽  
Author(s):  
Dalia Cicily Kattiparambil Dixon ◽  
Chameli Ratan ◽  
Bhagyalakshmi Nair ◽  
Sabitha Mangalath ◽  
Rachy Abraham ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Vaccine Development ◽  
Innate Immune ◽  
Interferon Response ◽  
Host Immune System ◽  
Type I ◽  
Adaptive Responses ◽  
Rna Sensors

: Innate immunity is the first line of defence elicited by the host immune system to fight against invading pathogens such as viruses and bacteria. From this elementary immune response, the more complex antigen-specific adaptive responses are recruited to provide a long-lasting memory against the pathogens. Innate immunity gets activated when the host cell utilizes a diverse set of receptors known as pattern recognition receptors (PRR) to recognize the viruses that have penetrated the host and respond with cellular processes like complement system, phagocytosis, cytokine release and inflammation and destruction of NK cells. Viral RNA or DNA or viral intermediate products are recognized by receptors like toll-like receptors(TLRs), nucleotide oligomerization domain(NOD)-like receptors (NLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) thereby, inducing type I interferon response (IFN) and other proinflammatory cytokines in infected cells or other immune cells. But certain viruses can evade the host innate immune response to replicate efficiently, triggering the spread of the viral infection. The present review describes the similarity in the mechanism chosen by viruses from different families -HIV, SARS-CoV2 and Nipah viruses to evade the innate immune response and how efficiently they establish the infection in the host. The review also addresses the stages of developments of various vaccines against these viral diseases and the challenges encountered by the researchers during vaccine development.

scholarly journals Insights into Innate Immune Response Against SARS-CoV-2 Infection

2021 ◽  
Vol 29 (3) ◽  
pp. 255-269
Author(s):  
Adina Huțanu ◽  
Anca Meda Georgescu ◽  
Akos Vince Andrejkovits ◽  
William Au ◽  
Minodora Dobreanu
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Innate Immune System ◽  
Time Course ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Interferon Response ◽  
Humoral Factors ◽  
Key Steps

Abstract The innate immune system is mandatory for the activation of antiviral host defense and eradication of the infection. In this regard, dendritic cells, natural killer cells, macrophages, neutrophils representing the cellular component, and cytokines, interferons, complement or Toll-Like Receptors, representing the mediators of unspecific response act together for both activation of the adaptive immune response and viral clearance. Of great importance is the proper functioning of the innate immune response from the very beginning. For instance, in the early stages of viral infection, the defective interferon response leads to uncontrolled viral replication and pathogen evasion, while hypersecretion during the later stages of infection generates hyperinflammation. This cascade activation of systemic inflammation culminates with cytokine storm syndrome and hypercoagulability state, due to a close interconnection between them. Thus an unbalanced reaction, either under- or over- stimulation of the innate immune system will lead to an uncoordinated response and unfavorable disease outcomes. Since both cellular and humoral factors are involved in the time-course of the innate immune response, in this review we aimed to address their gradual involvement in the antiviral response with emphasis on key steps in SARS-CoV-2 infection.

scholarly journals Human Cytomegalovirus Immediate Early 86-kDa Protein Blocks Transcription and Induces Degradation of the Immature Interleukin-1β Protein during Virion-Mediated Activation of the AIM2 Inflammasome

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sara Botto ◽  
Jinu Abraham ◽  
Nobuyo Mizuno ◽  
Kara Pryke ◽  
Bryan Gall ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Innate Immune ◽  
Host Cells ◽  
Interleukin 1Β ◽  
Immediate Early ◽  
Interferon Response ◽  
Type I

ABSTRACTSecretion of interleukin-1β (IL-1β) represents a fundamental innate immune response to microbial infection that, at the molecular level, occurs following activation of proteolytic caspases that cleave the immature protein into a secretable form. Human cytomegalovirus (HCMV) is the archetypal betaherpesvirus that is invariably capable of lifelong infection through the activity of numerous virally encoded immune evasion phenotypes. Innate immune pathways responsive to cytoplasmic double-stranded DNA (dsDNA) are known to be activated in response to contact between HCMV and host cells. Here, we used clustered regularly interspaced short palindromic repeat (CRISPR)–CRISPR-associated protein 9 (Cas9) genome editing to demonstrate that the dsDNA receptorabsentinmelanoma 2 (AIM2) is required for secretion of IL-1β following HCMV infection. Furthermore, dsDNA-responsive innate signaling induced by HCMV infection that leads to activation of the type I interferon response is also shown, unexpectedly, to play a contributory role in IL-1β secretion. Importantly, we also show that rendering virus particles inactive by UV exposure leads to substantially increased IL-1β processing and secretion and that live HCMV can inhibit this, suggesting the virus encodes factors that confer an inhibitory effect on this response. Further examination revealed that ectopic expression of the immediate early (IE) 86-kDa protein (IE86) is actually associated with a block in transcription of the pro-IL-1β gene and, independently, diminishment of the immature protein. Overall, these results reveal two new and distinct phenotypes conferred by the HCMV IE86 protein, as well as an unusual circumstance in which a single herpesviral protein exhibits inhibitory effects on multiple molecular processes within the same innate immune response.IMPORTANCEPersistent infection with HCMV is associated with the operation of diverse evasion phenotypes directed at antiviral immunity. Obstruction of intrinsic and innate immune responses is typically conferred by viral proteins either associated with the viral particle or expressed immediately after entry. In line with this, numerous phenotypes are attributed to the HCMV IE86 protein that involve interference with innate immune processes via transcriptional and protein-directed mechanisms. We describe novel IE86-mediated phenotypes aimed at virus-induced secretion of IL-1β. Intriguingly, while many viruses target the function of the molecular scaffold required for IL-1β maturation to prevent this response, we find that HCMV and IE86 target the IL-1β protein specifically. Moreover, we show that IE86 impairs both the synthesis of the IL-1β transcript and the stability of the immature protein. This indicates an unusual phenomenon in which a single viral protein exhibits two molecularly separate evasion phenotypes directed at a single innate cytokine.

scholarly journals The brain parenchyma has a type I interferon response that can limit virus spread

2016 ◽  
Vol 114 (1) ◽  
pp. E95-E104 ◽  
Author(s):  
Eugene Drokhlyansky ◽  
Didem Göz Aytürk ◽  
Timothy K. Soh ◽  
Ryan Chrenek ◽  
Elaine O’Loughlin ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Type I Interferon ◽  
Brain Parenchyma ◽  
Innate Immune ◽  
Interferon Response ◽  
Type I ◽  
Virus Spread ◽  
Viral Spread ◽  
The Brain

The brain has a tightly regulated environment that protects neurons and limits inflammation, designated “immune privilege.” However, there is not an absolute lack of an immune response. We tested the ability of the brain to initiate an innate immune response to a virus, which was directly injected into the brain parenchyma, and to determine whether this response could limit viral spread. We injected vesicular stomatitis virus (VSV), a transsynaptic tracer, or naturally occurring VSV-derived defective interfering particles (DIPs), into the caudate–putamen (CP) and scored for an innate immune response and inhibition of virus spread. We found that the brain parenchyma has a functional type I interferon (IFN) response that can limit VSV spread at both the inoculation site and among synaptically connected neurons. Furthermore, we characterized the response of microglia to VSV infection and found that infected microglia produced type I IFN and uninfected microglia induced an innate immune response following virus injection.

scholarly journals Induction of an Embryonic Mouse Innate Immune Response following Inoculation In Utero with Minute Virus of Mice

2014 ◽  
Vol 89 (4) ◽  
pp. 2182-2191 ◽  
Author(s):  
Irina Rostovsky ◽  
Claytus Davis
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
In Utero ◽  
Innate Immune ◽  
Productive Infection ◽  
Interferon Response ◽  
Minute Virus Of Mice ◽  
Embryonic Mouse ◽  
Minute Virus ◽  
Ifn Γ

ABSTRACTWe used an embryonic-infection model system to show that MVMp, the prototypic minute virus of mice (MVM) serotype and a member of the genusProtoparvovirus, triggers a comprehensive innate immune response in the developing mouse embryo. Direct inoculation of the midtrimester embryoin uterowith MVMp results in a widespread, productive infection. During a 96-h infection course, embryonic beta interferon (IFN-β) and IFN-γ transcription were induced 90- and 60-fold, respectively. IFN-β levels correlated with the embryo viral burden, while IFN-γ levels first increased and then decreased. Production of proinflammatory cytokines, interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α), also increased, but by smaller amounts, approximately 7-fold each. We observed increased levels of downstream antiviral effector molecules, PKR and phosphorylated STAT2. Finally, we showed that there is an immune cell response to the virus infection. Infected tissues in the embryo exhibited an increased density of mature leukocytes compared to the same tissues in uninfected embryos. The responses we observed were almost completely restricted to the infected embryos. Uninfected littermates routinely exhibited small increases in innate immune components that rarely reached statistical significance compared to negative controls. Similarly, the placentae of infected embryos did not show any significant increase in transcription of innate immune cytokines. Since the placenta has both embryonic and maternal components, we suggest there is minimal involvement of the dam in the response to infection.IMPORTANCEInteraction between the small single-stranded vertebrate DNA viruses, the protoparvoviruses, and the host innate immune system has been unclear. The issue is important practically given the potential use of these viruses as oncotherapeutic agents. The data reported here stand in contrast to studies of innate immune response during protoparvovirus infection of adult hosts, which invariably reported no or minimal and sporadic induction of an interferon response during infection. We conclude that under conditions of robust and productive MVM infection, a normal murine host is able to mount a significant and broad innate immune response.

scholarly journals A virus-encoded microRNA contributes to evade innate immune response during SARS-CoV-2 infection

2021 ◽  
Author(s):  
Meetali Singh ◽  
Maxime Chazal ◽  
Piergiuseppe Quarato ◽  
Loan Bourdon ◽  
Christophe Malabat ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Small Rnas ◽  
Viral Genome ◽  
Innate Immune ◽  
Micro Rna ◽  
Interferon Response ◽  
Interferon Stimulated Genes ◽  
Argonaute Proteins ◽  
Infected Cells

SARS-CoV-2 infection results in impaired interferon response in severe COVID-19 patients. However, how SARS-CoV-2 interferes with host immune response is incompletely understood. Here, we sequenced small RNAs from SARS-CoV-2-infected human cells and identified a micro-RNA (miRNA) encoded in a recently evolved region of the viral genome. We show that the virus-encoded miRNA produces two miRNA isoforms in infected cells by the enzyme Dicer and they are loaded into Argonaute proteins. Moreover, the predominant miRNA isoform targets the 3’UTR of interferon-stimulated genes and represses their expression in a miRNA-like fashion. Finally, the two viral miRNA isoforms were detected in nasopharyngeal swabs from COVID-19 patients. We propose that SARS-CoV-2 employs a virus-encoded miRNA to hijack the host miRNA machinery and evade the interferon-mediated immune response.

scholarly journals UHRF1 suppresses viral mimicry through both DNA methylation-dependent and -independent mechanisms

2020 ◽  
Author(s):  
RE Irwin ◽  
CA Scullion ◽  
SJ Thursby ◽  
ML Sun ◽  
A Thakur ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Cell Lines ◽  
Cancer Cell ◽  
Innate Immune Response ◽  
Point Mutations ◽  
Innate Immune ◽  
Lung Fibroblasts ◽  
Interferon Response ◽  
Viral Mimicry

AbstractSome chemotherapeutic agents which cause loss of DNA methylation have been recently shown to induce a state of “viral mimicry” involving upregulation of endogenous retroviruses (ERV) and a subsequent innate immune response. This approach may be useful in combination with immune checkpoint cancer therapies, but relatively little is known about normal cellular control of ERV suppression. The UHRF1 protein can interact with the maintenance methylation protein DNMT1 and is known to play an important role in epigenetic control in the cell. To examine potential roles of this protein in differentiated cells, we first established stable knockdowns in normal human lung fibroblasts. While these knockdown cells showed the expected loss of DNA methylation genome-wide, transcriptional changes were instead dominated by a single response, namely activation of innate immune signalling, consistent with viral mimicry. We confirmed using mechanistic approaches that activation of interferons and interferon-stimulated genes involved in double-stranded RNA detection was crucial to the response. ERVs were demethylated and transcriptionally activated in UHRF1 knockdown cells. As in these normal cell lines, ERV activation and interferon response also occurred following the transient loss of UHRF1 in both melanoma and colon cancer cell lines. Restoring UHRF1 in either transient- or stable knockdown systems abrogated ERV reactivation and interferon response, but without substantial restoration of DNA methylation. Rescued cell lines were hypersensitive to depletion of SETDB1, implicating H3K9me3 as crucial to UHRF1-mediated repression in the absence of DNA methylation. Confirming this, cells rescued with UHRF1 containing point mutations affecting H3K9me3 binding could not mediate silencing of ERV transcription or the innate immune response. Finally, by introducing similar point mutations in the mouse homologue, we could show that this pathway is conserved in mice. Our results therefore implicate UHRF1 as a key regulator of ERV suppression and strengthen the basis for cancer cell hypomethylation therapy.

scholarly journals Vpu-Deficient HIV Strains Stimulate Innate Immune Signaling Responses in Target Cells

2012 ◽  
Vol 86 (16) ◽  
pp. 8499-8506 ◽  
Author(s):  
Brian P. Doehle ◽  
Kristina Chang ◽  
Lamar Fleming ◽  
John McNevin ◽  
Florian Hladik ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Host Cell ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Target Cells ◽  
Major Public Health Problem ◽  
Type I ◽  
Innate Defense ◽  
Hiv 1

Acute virus infection induces a cell-intrinsic innate immune response comprising our first line of immunity to limit virus replication and spread, but viruses have developed strategies to overcome these defenses. HIV-1 is a major public health problem; however, the virus-host interactions that regulate innate immune defenses against HIV-1 are not fully defined. We have recently identified the viral protein Vpu to be a key determinant responsible for HIV-1 targeting and degradation of interferon regulatory factor 3 (IRF3), a central transcription factor driving host cell innate immunity. IRF3 plays a major role in pathogen recognition receptor (PRR) signaling of innate immunity to drive the expression of type I interferon (IFN) and interferon-stimulated genes (ISGs), including a variety of HIV restriction factors, that serve to limit viral replication directly and/or program adaptive immunity. Here we interrogate the cellular responses to target cell infection with Vpu-deficient HIV-1 strains. Remarkably, in the absence of Vpu, HIV-1 triggers a potent intracellular innate immune response that suppresses infection. Thus, HIV-1 can be recognized by PRRs within the host cell to trigger an innate immune response, and this response is unmasked only in the absence of Vpu. Vpu modulation of IRF3 therefore prevents virus induction of specific innate defense programs that could otherwise limit infection. These observations show that HIV-1 can indeed be recognized as a pathogen in infected cells and provide a novel and effective platform for defining the native innate immune programs of target cells of HIV-1 infection.

Sign in / Sign up

Export Citation Format

Share Document