scholarly journals Variations in the Abortive HIV-1 RNA Hairpin Do Not Impede Viral Sensing and Innate Immune Responses

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 897
Author(s):  
Melissa Stunnenberg ◽  
John L. van Hamme ◽  
Atze T. Das ◽  
Ben Berkhout ◽  
Teunis B. H. Geijtenbeek
Keyword(s):  
Immune Responses ◽  
Rna Structure ◽  
Inflammatory Responses ◽  
Innate Immune Responses ◽  
Antiviral Responses ◽  
Immunodeficiency Virus ◽  
Tar Rna ◽  
Rna Hairpin ◽  
Hiv 1

The highly conserved trans-acting response element (TAR) present in the RNA genome of human immunodeficiency virus 1 (HIV-1) is a stably folded hairpin structure involved in viral replication. However, TAR is also sensed by viral sensors, leading to antiviral immunity. While high variation in the TAR RNA structure renders the virus replication-incompetent, effects on viral sensing remain unclear. Here, we investigated the role of TAR RNA structure and stability on viral sensing. TAR mutants with deletions in the TAR hairpin that enhanced thermodynamic stability increased antiviral responses. Strikingly, TAR mutants with lower stability due to destabilization of the TAR hairpin also increased antiviral responses without affecting pro-inflammatory responses. Moreover, mutations that affected the TAR RNA sequence also enhanced specific antiviral responses. Our data suggest that mutations in TAR of replication-incompetent viruses can still induce immune responses via viral sensors, hereby underscoring the robustness of HIV-1 RNA sensing mechanisms.

scholarly journals Intestinal macrophages in mucosal immunity and their role in systemic lupus erythematosus disease

Lupus ◽  
2018 ◽  
Vol 27 (12) ◽  
pp. 1898-1902 ◽  
Author(s):  
F Pan ◽  
W Tang ◽  
Z Zhou ◽  
G Gilkeson ◽  
R Lang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Responses ◽  
Lupus Erythematosus ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Systemic Lupus ◽  
Innate Immune Signaling ◽  
Immune Signaling Pathway

Monocytes play an important role in inducing host systemic immunity against invading pathogens and inflammatory responses. After activation, monocytes migrate to tissue sites, where they initiate both innate and adaptive immune responses, and become macrophages. Although mucosal macrophages produce inflammatory cytokines in response to pathogens, the perturbations in innate immune signaling pathway have been implicated in autoimmune diseases such as systemic lupus erythematosus (SLE). In this review, we focus on the role of human macrophages in intestinal innate immune responses, homeostasis, and SLE disease. We further discuss sex differences in the intestinal macrophages and their role in the physiology and pathogenesis of SLE.

scholarly journals The Potential Role of FREM1 and Its Isoform TILRR in HIV-1 Acquisition through Mediating Inflammation

2021 ◽  
Vol 22 (15) ◽  
pp. 7825
Author(s):  
Mohammad Abul Kashem ◽  
Hongzhao Li ◽  
Lewis Ruxi Liu ◽  
Binhua Liang ◽  
Robert Were Omange ◽  
...  
Keyword(s):  
Sex Workers ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Signal Transduction Pathway ◽  
Polymorphism Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Immunodeficiency Virus ◽  
Hiv 1

FREM1 (Fras-related extracellular matrix 1) and its splice variant TILRR (Toll-like interleukin-1 receptor regulator) have been identified as integral components of innate immune systems. The potential involvement of FREM1 in HIV-1 (human immunodeficiency virus 1) acquisition was suggested by a genome-wide SNP (single nucleotide polymorphism) analysis of HIV-1 resistant and susceptible sex workers enrolled in the Pumwani sex worker cohort (PSWC) in Nairobi, Kenya. The studies showed that the minor allele of a FREM1 SNP rs1552896 is highly enriched in the HIV-1 resistant female sex workers. Subsequent studies showed that FREM1 mRNA is highly expressed in tissues relevant to mucosal HIV-1 infection, including cervical epithelial tissues, and TILRR is a major modulator of many genes in the NF-κB signal transduction pathway. In this article, we review the role of FREM1 and TILRR in modulating inflammatory responses and inflammation, and how their influence on inflammatory responses of cervicovaginal tissue could enhance the risk of vaginal HIV-1 acquisition.

scholarly journals The Role of Defensins in HIV Pathogenesis

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Barcley T. Pace ◽  
Andrew A. Lackner ◽  
Edith Porter ◽  
Bapi Pahar
Keyword(s):  
Innate Immune ◽  
Future Research ◽  
Innate Immune Responses ◽  
Disulfide Linkages ◽  
Immunodeficiency Virus ◽  
Functional Peptides ◽  
Anti Hiv ◽  
Hiv 1

Profound loss of CD4+T cells, progressive impairment of the immune system, inflammation, and sustained immune activation are the characteristics of human immunodeficiency virus-1 (HIV-1) infection. Innate immune responses respond immediately from the day of HIV infection, and a thorough understanding of the interaction between several innate immune cells and HIV-1 is essential to determine to what extent those cells play a crucial role in controlling HIV-1in vivo. Defensins, divided into the three subfamiliesα-,β-, andθ-defensins based on structure and disulfide linkages, comprise a critical component of the innate immune response and exhibit anti-HIV-1 activities and immunomodulatory capabilities. In humans, onlyα- andβ-defensins are expressed in various tissues and have broad impacts on HIV-1 transmission, replication, and disease progression.θ-defensins have been identified as functional peptides in Old World monkeys, but not in humans. Instead,θ-defensins exist only as pseudogenes in humans, chimpanzees, and gorillas. The use of the syntheticθ-defensin peptide “retrocyclin” as an antiviral therapy was shown to be promising, and further research into the development of defensin-based HIV-1 therapeutics is needed. This review focuses on the role of defensins in HIV-1 pathogenesis and highlights future research efforts that warrant investigation.

scholarly journals HIV-1 Is a Poor Inducer of Innate Immune Responses

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Oya Cingöz ◽  
Stephen P. Goff
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Cell Lines ◽  
Human Immunodeficiency Virus Type ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Sensors ◽  
Hiv 1

ABSTRACT Effective host immune responses against viral infection rely on the detection of the virus, activation of downstream signaling pathways, and the secretion of interferons (IFNs) and other cytokines. Many viruses can potently stimulate these responses, whereas the immune response against human immunodeficiency virus type 1 (HIV-1) remains relatively less well characterized. Here we show that HIV-1 infection with reporter viruses does not activate sensing pathways in cell lines and primary cells that are otherwise responsive to foreign nucleic acids. After entry into cells, reverse transcription and reporter expression occur without the virus ever being detected by cellular sensors or stimulating an interferon response. Using multiple methods, including the use of reporter cell lines for type I IFN and NF-κB pathway activation, quantifying mRNA levels for IFN-stimulated genes (ISGs), and assaying for markers of innate immune activation, we show that single-round pseudotyped HIV-1-based reporter viruses fail to induce innate immune responses. IMPORTANCE Human immunodeficiency virus type 1 (HIV-1) continues to be a major burden to human health worldwide. How infected cells recognize and respond to HIV-1 infection is important in order to better understand the biology of the virus and the cellular pathways activated upon infection and to identify potential targets that interfere with viral replication. In this study, we investigated innate immune responses of different cell types following infection with single-cycle (replication-defective) HIV-1 reporter virus. We report that infection with a commonly used HIV-1 strain (lacking the env, nef, and vpr genes) does not measurably activate cellular defense mechanisms and that the virus is able to avoid recognition by cellular sensors.

scholarly journals Effects and Side Effects of Platelet Transfusion

2021 ◽  
Author(s):  
Fabrice Cognasse ◽  
Kathryn Hally ◽  
Sebastien Fauteux-Daniel ◽  
Marie-Ange Eyraud ◽  
Charles-Antoine Arthaud ◽  
...  
Keyword(s):  
Side Effects ◽  
Immune Responses ◽  
Platelet Transfusion ◽  
Biological Response ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Stress Injury ◽  
Processing And Storage ◽  
And Storage

AbstractAside from their canonical role in hemostasis, it is increasingly recognized that platelets have inflammatory functions and can regulate both adaptive and innate immune responses. The main topic this review aims to cover is the proinflammatory effects and side effects of platelet transfusion. Platelets prepared for transfusion are subject to stress injury upon collection, preparation, and storage. With these types of stress, they undergo morphologic, metabolic, and functional modulations which are likely to induce platelet activation and the release of biological response modifiers (BRMs). As a consequence, platelet concentrates (PCs) accumulate BRMs during processing and storage, and these BRMs are ultimately transfused alongside platelets. It has been shown that BRMs present in PCs can induce immune responses and posttransfusion reactions in the transfusion recipient. Several recent reports within the transfusion literature have investigated the concept of platelets as immune cells. Nevertheless, current and future investigations will face the challenge of encompassing the immunological role of platelets in the scope of transfusion.

scholarly journals Essential role of IPS-1 in innate immune responses against RNA viruses

2006 ◽  
Vol 203 (7) ◽  
pp. 1795-1803 ◽  
Author(s):  
Himanshu Kumar ◽  
Taro Kawai ◽  
Hiroki Kato ◽  
Shintaro Sato ◽  
Ken Takahashi ◽  
...  
Keyword(s):  
Rna Viruses ◽  
Rna Virus ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Innate Immune Responses ◽  
Antiviral Responses ◽  
Deficient Mice

IFN-β promoter stimulator (IPS)-1 was recently identified as an adapter for retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda5), which recognize distinct RNA viruses. Here we show the critical role of IPS-1 in antiviral responses in vivo. IPS-1–deficient mice showed severe defects in both RIG-I– and Mda5-mediated induction of type I interferon and inflammatory cytokines and were susceptible to RNA virus infection. RNA virus–induced interferon regulatory factor-3 and nuclear factor κB activation was also impaired in IPS-1–deficient cells. IPS-1, however, was not essential for the responses to either DNA virus or double-stranded B-DNA. Thus, IPS-1 is the sole adapter in both RIG-I and Mda5 signaling that mediates effective responses against a variety of RNA viruses.

scholarly journals Structure, Function, and Interactions of the HIV-1 Capsid Protein

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 100
Author(s):  
Eric Rossi ◽  
Megan E. Meuser ◽  
Camille J. Cunanan ◽  
Simon Cocklin
Keyword(s):  
Life Cycle ◽  
Capsid Protein ◽  
Adaptor Proteins ◽  
Restriction Factors ◽  
Gag Polyprotein ◽  
Immunodeficiency Virus ◽  
Host Cell Factors ◽  
Hiv 1

The capsid (CA) protein of the human immunodeficiency virus type 1 (HIV-1) is an essential structural component of a virion and facilitates many crucial life cycle steps through interactions with host cell factors. Capsid shields the reverse transcription complex from restriction factors while it enables trafficking to the nucleus by hijacking various adaptor proteins, such as FEZ1 and BICD2. In addition, the capsid facilitates the import and localization of the viral complex in the nucleus through interaction with NUP153, NUP358, TNPO3, and CPSF-6. In the later stages of the HIV-1 life cycle, CA plays an essential role in the maturation step as a constituent of the Gag polyprotein. In the final phase of maturation, Gag is cleaved, and CA is released, allowing for the assembly of CA into a fullerene cone, known as the capsid core. The fullerene cone consists of ~250 CA hexamers and 12 CA pentamers and encloses the viral genome and other essential viral proteins for the next round of infection. As research continues to elucidate the role of CA in the HIV-1 life cycle and the importance of the capsid protein becomes more apparent, CA displays potential as a therapeutic target for the development of HIV-1 inhibitors.

scholarly journals From Capsids to Complexes: Expanding the Role of TRIM5α in the Restriction of Divergent RNA Viruses and Elements

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 446
Author(s):  
Kevin M. Rose ◽  
Stephanie J. Spada ◽  
Rebecca Broeckel ◽  
Kristin L. McNally ◽  
Vanessa M. Hirsch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Molecular Basis ◽  
Human Population ◽  
Rna Viruses ◽  
Arms Race ◽  
Innate Immune ◽  
Immunodeficiency Virus ◽  
Underlying Mechanisms ◽  
Hiv 1

An evolutionary arms race has been ongoing between retroviruses and their primate hosts for millions of years. Within the last century, a zoonotic transmission introduced the Human Immunodeficiency Virus (HIV-1), a retrovirus, to the human population that has claimed the lives of millions of individuals and is still infecting over a million people every year. To counteract retroviruses such as this, primates including humans have evolved an innate immune sensor for the retroviral capsid lattice known as TRIM5α. Although the molecular basis for its ability to restrict retroviruses is debated, it is currently accepted that TRIM5α forms higher-order assemblies around the incoming retroviral capsid that are not only disruptive for the virus lifecycle, but also trigger the activation of an antiviral state. More recently, it was discovered that TRIM5α restriction is broader than previously thought because it restricts not only the human retroelement LINE-1, but also the tick-borne flaviviruses, an emergent group of RNA viruses that have vastly different strategies for replication compared to retroviruses. This review focuses on the underlying mechanisms of TRIM5α-mediated restriction of retroelements and flaviviruses and how they differ from the more widely known ability of TRIM5α to restrict retroviruses.

Sign in / Sign up

Export Citation Format

Share Document