scholarly journals An Antiviral Process Targeting HTLV-1: The Complex Relationship between HTLV-1 and Nonsense-mediated mRNA Decay

2020 ◽  
Author(s):  
Léa Prochasson ◽  
Pierre Jalinot ◽  
Vincent Mocquet
Keyword(s):  
Mrna Decay ◽  
Genome Instability ◽  
Adaptive Immune Response ◽  
Host Factors ◽  
Intrinsic Immunity ◽  
Defence Mechanisms ◽  
Adaptive Immune ◽  
Nonsense Mediated Mrna Decay ◽  
Long Term Impact

Before the adaptive immune response is established, retroviruses can be targeted by several cellular host factors at different stages of the viral replication cycle. This intrinsic immunity relies on a large diversity of antiviral processes. In the case of HTLV-1 infection, these active innate host defence mechanisms are debated. Among these mechanisms, we focused on a RNA decay pathway called nonsense-mediated mRNA decay (NMD), which can target multiple viral RNAs, including HTLV-1 unspliced RNA, as it has been recently demonstrated. NMD is a cotranslational process that depends on the RNA helicase UPF1 and regulates the expression of multiple types of host mRNAs. RNA sensitivity to NMD depends on mRNA organization and the ribonucleoprotein (mRNP) composition. HTLV-1 has evolved several means to evade the NMD threat, leading to NMD inhibition. In the early steps of infection, NMD inhibition favours the production of HTLV-1 infectious particles, which may contribute to the survival of the most fit clones despite genome instability; however, its direct long-term impact remains to be investigated.

scholarly journals The Complex Relationship between HTLV-1 and Nonsense-Mediated mRNA Decay (NMD)

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 287 ◽  
Author(s):  
Léa Prochasson ◽  
Pierre Jalinot ◽  
Vincent Mocquet
Keyword(s):  
Defense Mechanisms ◽  
Mrna Decay ◽  
Genome Instability ◽  
Adaptive Immune Response ◽  
Intrinsic Immunity ◽  
Nonsense Mediated Mrna Decay ◽  
Long Term Impact ◽  
Survival Of The Fittest ◽  
Translational Process

Before the establishment of an adaptive immune response, retroviruses can be targeted by several cellular host factors at different stages of the viral replication cycle. This intrinsic immunity relies on a large diversity of antiviral processes. In the case of HTLV-1 infection, these active innate host defense mechanisms are debated. Among these mechanisms, we focused on an RNA decay pathway called nonsense-mediated mRNA decay (NMD), which can target multiple viral RNAs, including HTLV-1 unspliced RNA, as has been recently demonstrated. NMD is a co-translational process that depends on the RNA helicase UPF1 and regulates the expression of multiple types of host mRNAs. RNA sensitivity to NMD depends on mRNA organization and the ribonucleoprotein (mRNP) composition. HTLV-1 has evolved several means to evade the NMD threat, leading to NMD inhibition. In the early steps of infection, NMD inhibition favours the production of HTLV-1 infectious particles, which may contribute to the survival of the fittest clones despite genome instability; however, its direct long-term impact remains to be investigated.

scholarly journals Association of DFNA5, SYK, and NELL1 variants along with HPV infection in oral cancer among the prolonged tobacco-chewers

Tumor Biology ◽  
2018 ◽  
Vol 40 (8) ◽  
pp. 101042831879302 ◽  
Author(s):  
Sharbadeb Kundu ◽  
Vijayalakshmi Ramshankar ◽  
Akalesh Kumar Verma ◽  
Soundara Viveka Thangaraj ◽  
Arvind Krishnamurthy ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Genetic Susceptibility ◽  
Squamous Cell ◽  
Odds Ratio ◽  
Mrna Decay ◽  
Hpv Infection ◽  
Nonsense Mediated Mrna Decay

Southeast Asia, especially India, is well known for the highest use of smokeless tobacco. These products are known to induce oral squamous cell carcinoma. However, not all long-term tobacco-chewers develop oral squamous cell carcinoma. In addition, germline variants play a crucial role in susceptibility, prognosis, development, and progression of the disease. These prompted us to study the genetic susceptibility to oral squamous cell carcinoma among the long-term tobacco-chewers. Here, we presented a retrospective study on prolonged tobacco-chewers of Northeast India to identify the potential protective or risk-associated germline variants in tobacco-related oral squamous cell carcinoma along with HPV infection. Targeted re-sequencing (n = 60) of 170 genetic regions from 75 genes was carried out in Ion-PGM™ and validation (n = 116) of the observed variants was done using Sequenom iPLEX MassARRAY™ platform followed by polymerase chain reaction–based HPV genotyping and p16-immunohistochemistry study. Subsequently, estimation of population structure, different statistical and in silico approaches were undertaken. We identified one nonsense-mediated mRNA decay transcript variant in the DFNA5 region (rs2237306), associated with Benzo(a)pyrene, as a protective factor (odds ratio = 0.33; p = 0.009) and four harmful (odds ratio > 2.5; p < 0.05) intronic variants, rs182361, rs290974, and rs169724 in SYK and rs1670661 in NELL1 region, involved in genetic susceptibility to tobacco- and HPV-mediated oral oncogenesis. Among the oral squamous cell carcinoma patients, 12.6% (11/87) were HPV positive, out of which 45.5% (5/11) were HPV16-infected, 27.3% (3/11) were HPV18-infected, and 27.3% (3/11) had an infection of both subtypes. Multifactor dimensionality reduction analysis showed that the interactions among HPV and NELL1 variant rs1670661 with age and gender augmented the risk of both non-tobacco- and tobacco-related oral squamous cell carcinoma, respectively. These suggest that HPV infection may be one of the important risk factors for oral squamous cell carcinoma in this population. Finally, we newly report a DFNA5 variant probably conferring protection via nonsense-mediated mRNA decay pathway against tobacco-related oral squamous cell carcinoma. Thus, the analytical approach used here can be useful in predicting the population-specific significant variants associated with oral squamous cell carcinoma in any heterogeneous population.

scholarly journals Predicting the risk of re-infection from SARS-CoV-2 using the known pattern of adaptive immune response to previous human coronavirus outbreaks

2020 ◽  
Author(s):  
Ademola Samuel Ojo ◽  
Paul Toluwatope Okediji ◽  
Ayotemide P. Akin-Onitolo ◽  
Olusegun S. Ojo ◽  
Oluyinka Oladele Opaleye
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
The Body ◽  
Short Term ◽  
Adaptive Immune ◽  
Short And Long Term

This paper attempts to answer the question: are recovered COVID-19 patients protected from re-infection? This review draws evidence from comparisons between immune responses to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), which are phylogenetically closely related to Severe Acute Respiratory Syndrome coronavirus type 2 (SARS-CoV-2). Relevant studies were identified and reviewed based on searches conducted using PubMed. Full-text original studies on short- and long-term immune responses to human coronaviruses were included. The immune dysfunction and clinical manifestations in SARS-CoV-2, SARS-CoV, and MERS-CoV were found to be similar. Infections with SARS-CoV and MERS-CoV trigger the production of antibodies and memory B- and T-cells. Serum IgM is detectable within 7 days, peak at 21-30 days and become undetectable by 180 days. IgG is detectable at 7 days, peak at 90 days, and decline to undetected levels by 2 years post-infection. Memory B- and T-cells persist in the body for up to 2 and 6 years respectively after initial infection. The short-term risk of SARS-CoV-2 re-infection is predictably low based on similarities in the short term adaptive immune response to kindred coronaviruses. However, more research will be required to determine the long-term adaptive immunity to SARS-CoV-2 and factors that may influence the existence of short- and long-term immunity against the virus.

scholarly journals Renal Morphology in Coronavirus Disease: A Literature Review

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 258
Author(s):  
Patrick de Oliveira ◽  
Kaile Cunha ◽  
Precil Neves ◽  
Monique Muniz ◽  
Giuseppe Gatto ◽  
...  
Keyword(s):  
Case Reports ◽  
Kidney Tissue ◽  
Adaptive Immune Response ◽  
Case Series ◽  
Vascular Diseases ◽  
Glomerular Diseases ◽  
Morphological Findings ◽  
Renal Morphology ◽  
Long Term Impact

Renal biopsy is useful to better understand the histological pattern of a lesion (glomerular, tubulointerstitial, and vascular) and the pathogenesis that leads to kidney failure. The potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the kidneys is still undetermined, and a variety of lesions are seen in the kidney tissue of coronavirus disease patients. This review is based on the morphological findings of patients described in case reports and a series of published cases. A search was conducted on MEDLINE and PubMed of case reports and case series of lesions in the presence of non-critical infection by SARS-CoV-2 published until 15/09/2020. We highlight the potential of the virus directly influencing the damage or the innate and adaptive immune response activating cytokine and procoagulant cascades, in addition to the genetic component triggering glomerular diseases, mainly collapsing focal segmental glomerulosclerosis, tubulointerstitial, and even vascular diseases. Kidney lesions caused by SARS-CoV-2 are frequent and have an impact on morbidity and mortality; thus, studies are needed to assess the morphological kidney changes and their mechanisms and may help define their spectrum and immediate or long-term impact.

scholarly journals Mecanismos de la respuesta inmune adaptativa: respuesta específica y de protección a largo plazo

2020 ◽  
Vol 3 (8) ◽  
pp. 25-43
Author(s):  
William de Jesús Ríos-Ríos ◽  
Jair Aguilar-Cruz
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Adaptive Immune Response ◽  
Molecular Structures ◽  
Pathogenic Microorganism ◽  
Human Immune System ◽  
Adaptive Immune ◽  
Specific Immunity ◽  
Human Immune

The human immune system has evolvedtoachieveahighlyefficient, specialized and specific immunity against particular molecular structures of each pathogenic microorganism and to develop mechanisms allowing to respond more quickly and efficiently to subsequent encounters with the same invading agent: the adaptive immune response. This paper describes the connection between the innate and adaptive immune response, as well as the cellular and humoral mechanisms of control and long-term protection of the adaptive immune response.

scholarly journals Will SARS-CoV-2 Infection Elicit Long-Lasting Protective or Sterilising Immunity? Implications for Vaccine Strategies (2020)

2020 ◽  
Vol 11 ◽  
Author(s):  
David S. Kim ◽  
Sarah Rowland-Jones ◽  
Ester Gea-Mallorquí
Keyword(s):  
Immune Response ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Adaptive Immune Response ◽  
Human Immune System ◽  
Adaptive Immune ◽  
Global Pandemic ◽  
Human Immune ◽  
Novel Coronavirus

In December 2019, an outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan, China resulted in the current COVID-19 global pandemic. The human immune system has not previously encountered this virus, raising the important question as to whether or not protective immunity is generated by infection. Growing evidence suggests that protective immunity can indeed be acquired post-infection—although a handful of reinfection cases have been reported. However, it is still unknown whether the immune response to SARS-CoV-2 leads to some degree of long-lasting protection against the disease or the infection. This review draws insights from previous knowledge regarding the nature and longevity of immunity to the related virus, SARS-CoV, to fill the gaps in our understanding of the immune response to SARS-CoV-2. Deciphering the immunological characteristics that give rise to protective immunity against SARS-CoV-2 is critical to guiding vaccine development and also predicting the course of the pandemic. Here we discuss the recent evidence that characterises the adaptive immune response against SARS-CoV-2 and its potential implications for the generation of memory responses and long-term protection.

scholarly journals Mechanisms Governing Immunotherapy Resistance in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zoe C. Schmiechen ◽  
Ingunn M. Stromnes
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Function ◽  
Adaptive Immune Response ◽  
Ductal Adenocarcinoma ◽  
Adaptive Immune ◽  
Cell Clearance

Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with an overall 5-year survival rate of 10%. Disease lethality is due to late diagnosis, early metastasis and resistance to therapy, including immunotherapy. PDA creates a robust fibroinflammatory tumor microenvironment that contributes to immunotherapy resistance. While previously considered an immune privileged site, evidence demonstrates that in some cases tumor antigen-specific T cells infiltrate and preferentially accumulate in PDA and are central to tumor cell clearance and long-term remission. Nonetheless, PDA can rapidly evade an adaptive immune response using a myriad of mechanisms. Mounting evidence indicates PDA interferes with T cell differentiation into potent cytolytic effector T cells via deficiencies in naive T cell priming, inducing T cell suppression or promoting T cell exhaustion. Mechanistic research indicates that immunotherapy combinations that change the suppressive tumor microenvironment while engaging antigen-specific T cells is required for treatment of advanced disease. This review focuses on recent advances in understanding mechanisms limiting T cell function and current strategies to overcome immunotherapy resistance in PDA.

Mycobacterium bovis BCG promotes IL-10 expression by establishing a SYK/PKCα/β positive autoregulatory loop that sustains STAT3 activation

2019 ◽  
Vol 77 (3) ◽  
Author(s):  
Tomás Villaseñor ◽  
Edgardo Madrid-Paulino ◽  
Rafael Maldonado-Bravo ◽  
Leonor Pérez-Martínez ◽  
Gustavo Pedraza-Alva
Keyword(s):  
Mycobacterium Bovis ◽  
Feedback Loop ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Gene Expression Profiles ◽  
Cytokine Gene Expression ◽  
Mycobacterium Bovis Bcg ◽  
Adaptive Immune

ABSTRACT Mycobacterium ensures its survival inside macrophages and long-term infection by subverting the innate and adaptive immune response through the modulation of cytokine gene expression profiles. Different Mycobacterium species promote the expression of TGFβ and IL-10, which, at the early stages of infection, block the formation of the phagolysosome, thereby securing mycobacterial survival upon phagocytosis, and at later stages, antagonize IFNγ production and functions. Despite the key role of IL-10 in mycobacterium infection, the signal transduction pathways leading to IL-10 expression in infected macrophages are poorly understood. Here, we report that Mycobacterium bovis BCG promotes IL-10 expression and cytokine production by establishing a SYK/PKCα/β positive feedback loop that leads to STAT3 activation.

scholarly journals Long-term expansion of effector/memory Vδ2− γδ T cells is a specific blood signature of CMV infection

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1317-1324 ◽  
Author(s):  
Vincent Pitard ◽  
David Roumanes ◽  
Xavier Lafarge ◽  
Lionel Couzi ◽  
Isabelle Garrigue ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Adaptive Immune Response ◽  
Γδ T Cells ◽  
Effector Memory ◽  
Γδ T Cell ◽  
Cmv Infection ◽  
Adaptive Immune

Abstract The ability of human γδ T cells to develop immunologic memory is still a matter of debate. We previously demonstrated the involvement of Vδ2− γδ T lymphocytes in the response of immunosuppressed organ recipients to cytomegalovirus (CMV). Here, we demonstrate their ability to mount an adaptive immune response to CMV in immunocompetent subjects. Vδ2− γδ T-cell peripheral blood numbers, repertoire restriction, and cytotoxicity against CMV-infected fibroblasts were markedly increased in CMV-seropositive, compared with CMV-seronegative, healthy persons. Whereas Vδ2− γδ T cells were found as naive cells in CMV− patients, they virtually all exhibited the cytotoxic effector/memory phenotype in CMV+ patients, which is also observed in transplanted patients challenged with CMV. This long-term complete remodeling of the Vδ2− γδ T-cell population by CMV predicts their ability to exhibit an adaptive anti-CMV immune response. Consistent with this, we observed that the secondary response to CMV was associated with a faster γδ T-cell expansion and a better resolution of infection than the primary response. In conclusion, the increased level of effector-memory Vδ2− γδ T cells in the peripheral blood is a specific signature of an adaptive immune response to CMV infection of both immunocompetent and immunosuppressed patients.

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