scholarly journals Porcine RIG-I and MDA5 Signaling CARD Domains Exert Similar Antiviral Function Against Different Viruses

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuangjie Li ◽  
Qi Shao ◽  
Yuanyuan Zhu ◽  
Xingyu Ji ◽  
Jia Luo ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Transcriptome Analysis ◽  
Viral Infections ◽  
Molecular Structures ◽  
Antiviral Function ◽  
Distinct Features ◽  
Signaling Domains ◽  
Signaling Activity

The RIG-I-like receptors (RLRs) RIG-I and MDA5 play critical roles in sensing and fighting viral infections. Although RIG-I and MDA5 have similar molecular structures, these two receptors have distinct features during activation. Further, the signaling domains of the N terminal CARD domains (CARDs) in RIG-I and MDA5 share poor similarity. Therefore, we wonder whether the CARDs of RIG-I and MDA5 play similar roles in signaling and antiviral function. Here we expressed porcine RIG-I and MDA5 CARDs in 293T cells and porcine alveolar macrophages and found that MDA5 CARDs exhibit higher expression and stronger signaling activity than RIG-I CARDs. Nevertheless, both RIG-I and MDA5 CARDs exert comparable antiviral function against several viruses. Transcriptome analysis showed that MDA5 CARDs are more effective in regulating downstream genes. However, in the presence of virus, both RIG-I and MDA5 CARDs exhibit similar effects on downstream gene transcriptions, reflecting their antiviral function.

The Role of microRNAs in the Viral Infections

2019 ◽  
Vol 24 (39) ◽  
pp. 4659-4667 ◽  
Author(s):  
Mona Fani ◽  
Milad Zandi ◽  
Majid Rezayi ◽  
Nastaran Khodadad ◽  
Hadis Langari ◽  
...  
Keyword(s):  
Viral Infections ◽  
Rna Viruses ◽  
Regulation Of Gene Expression ◽  
Molecular Structures ◽  
Main Function ◽  
Cellular Functions ◽  
Viral Genes ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.

scholarly journals Analysis of Porcine RIG-I Like Receptors Revealed the Positive Regulation of RIG-I and MDA5 by LGP2

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuangjie Li ◽  
Jie Yang ◽  
Yuanyuan Zhu ◽  
Hui Wang ◽  
Xingyu Ji ◽  
...  
Keyword(s):  
Cell Activation ◽  
Viral Infections ◽  
Rna Virus ◽  
Gene Knockout ◽  
Constitutive Activity ◽  
Virus Infections ◽  
Positive Regulation ◽  
Dsrna Binding ◽  
Livestock Animal ◽  
Signaling Activity

The RLRs play critical roles in sensing and fighting viral infections especially RNA virus infections. Despite the extensive studies on RLRs in humans and mice, there is a lack of systemic investigation of livestock animal RLRs. In this study, we characterized the porcine RLR members RIG-I, MDA5 and LGP2. Compared with their human counterparts, porcine RIG-I and MDA5 exhibited similar signaling activity to distinct dsRNA and viruses, via similar and cooperative recognitions. Porcine LGP2, without signaling activity, was found to positively regulate porcine RIG-I and MDA5 in transfected porcine alveolar macrophages (PAMs), gene knockout PAMs and PK-15 cells. Mechanistically, LGP2 interacts with RIG-I and MDA5 upon cell activation, and promotes the binding of dsRNA ligand by MDA5 as well as RIG-I. Accordingly, porcine LGP2 exerted broad antiviral functions. Intriguingly, we found that porcine LGP2 mutants with defects in ATPase and/or dsRNA binding present constitutive activity which are likely through RIG-I and MDA5. Our work provided significant insights into porcine innate immunity, species specificity and immune biology.

scholarly journals NAD+-consuming enzymes in immune defense against viral infection

2021 ◽  
Vol 478 (23) ◽  
pp. 4071-4092
Author(s):  
Jialin Shang ◽  
Michael R. Smith ◽  
Ananya Anmangandla ◽  
Hening Lin
Keyword(s):  
Immune Responses ◽  
Broad Spectrum ◽  
Defense Mechanisms ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Scientific Progress ◽  
Immune Defense ◽  
Past Century ◽  
Antiviral Immune Response ◽  
Antiviral Function

The COVID-19 pandemic reminds us that in spite of the scientific progress in the past century, there is a lack of general antiviral strategies. In analogy to broad-spectrum antibiotics as antibacterial agents, developing broad spectrum antiviral agents would buy us time for the development of vaccines and treatments for future viral infections. In addition to targeting viral factors, a possible strategy is to understand host immune defense mechanisms and develop methods to boost the antiviral immune response. Here we summarize the role of NAD+-consuming enzymes in the immune defense against viral infections, with the hope that a better understanding of this process could help to develop better antiviral therapeutics targeting these enzymes. These NAD+-consuming enzymes include PARPs, sirtuins, CD38, and SARM1. Among these, the antiviral function of PARPs is particularly important and will be a focus of this review. Interestingly, NAD+ biosynthetic enzymes are also implicated in immune responses. In addition, many viruses, including SARS-CoV-2 contain a macrodomain-containing protein (NSP3 in SARS-CoV-2), which serves to counteract the antiviral function of host PARPs. Therefore, NAD+ and NAD+-consuming enzymes play crucial roles in immune responses against viral infections and detailed mechanistic understandings in the future will likely facilitate the development of general antiviral strategies.

scholarly journals Involvement of autophagy in viral infections: antiviral function and subversion by viruses

2007 ◽  
Vol 85 (8) ◽  
Author(s):  
Lucile Espert ◽  
Patrice Codogno ◽  
Martine Biard-Piechaczyk
Keyword(s):  
Viral Infections ◽  
Antiviral Function

scholarly journals Genome-wide transcriptional response of primary alveolar macrophages following infection with porcine reproductive and respiratory syndrome virus

2008 ◽  
Vol 89 (10) ◽  
pp. 2550-2564 ◽  
Author(s):  
Sem Genini ◽  
Peter L. Delputte ◽  
Roberto Malinverni ◽  
Maria Cecere ◽  
Alessandra Stella ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alveolar Macrophages ◽  
Time Course ◽  
Viral Infections ◽  
Interleukin 10 ◽  
Innate Immune ◽  
Differentially Expressed ◽  
Respiratory Syndrome Virus ◽  
Swine Industry

Porcine reproductive and respiratory syndrome is a major cause of economic loss for the swine industry worldwide. Porcine reproductive and respiratory syndrome virus (PRRSV) triggers weak and atypical innate immune responses, but key genes and mechanisms by which the virus interferes with the host innate immunity have not yet been elucidated. In this study, genes that control the response of the main target of PRRSV, porcine alveolar macrophages (PAMs), were profiled in vitro with a time-course experiment spanning the first round of virus replication. PAMs were obtained from six piglets and challenged with the Lelystad PRRSV strain, and gene expression was investigated using Affymetrix microarrays and real-time PCR. Of the 1409 differentially expressed transcripts identified by analysis of variance, two, five, 25, 16 and 100 differed from controls by a minimum of 1.5-fold at 1, 3, 6, 9 and 12 h post-infection (p.i.), respectively. A PRRSV infection effect was detectable between 3 and 6 h p.i., and was characterized by a consistent downregulation of gene expression, followed by the start of the host innate immune response at 9 h p.i. The expression of beta interferon 1 (IFN-β), but not of IFN-α, was strongly upregulated, whilst few genes commonly expressed in response to viral infections and/or induced by interferons were found to be differentially expressed. A predominance of anti-apoptotic transcripts (e.g. interleukin-10), a shift towards a T-helper cell type 2 response and a weak upregulation of tumour necrosis factor-α expression were observed within 12 h p.i., reinforcing the hypotheses that PRRSV has developed sophisticated mechanisms to escape the host defence.

scholarly journals Age-dependent resistance of human alveolar macrophages to herpes simplex virus

1980 ◽  
Vol 28 (2) ◽  
pp. 417-420
Author(s):  
L Mintz ◽  
W L Drew ◽  
R Hoo ◽  
T N Finley
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Alveolar Macrophages ◽  
Clinical Observation ◽  
Virus Infections ◽  
Human Alveolar Macrophages ◽  
Age Dependent ◽  
Antiviral Function ◽  
Simplex Virus ◽  
Adult Volunteers

Studies in mice demonstrate an age-dependent susceptibility to disseminated herpesvirus infection which is mediated. at least in part, by a defect in macrophage antiviral function. We examined the growth of herpes simplex virus within human alveolar macrophages obtained by bronchopulmonary lavage from neonates, adults with a variety of immunosuppressive disorders, and healthy adult volunteers. At 24 h postinfection, mean viral titers in neonatal macrophages increased 19-fold over adsorbed virus levels, a highly significant increase when compared to either immunosuppressed or normal adult macrophages (P less than 0.0005). These findings indicate that human macrophages, like those of mice, exhibit age-dependent permissiveness for the replication of herpes simplex virus. This permissiveness may at least partially account for the clinical observation that human newborns are highly susceptible to disseminated herpes simplex virus infections, whereas adults are not.

scholarly journals PPAR-γ in Macrophages Limits Pulmonary Inflammation and Promotes Host Recovery following Respiratory Viral Infection

2019 ◽  
Vol 93 (9) ◽  
Author(s):  
Su Huang ◽  
Bibo Zhu ◽  
In Su Cheon ◽  
Nick P. Goplen ◽  
Li Jiang ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Alveolar Macrophages ◽  
Viral Infections ◽  
Pulmonary Inflammation ◽  
Type I ◽  
Disease Development ◽  
Host Disease ◽  
Ppar Γ ◽  
Respiratory Viral Infections ◽  
Syncytial Virus

ABSTRACT Alveolar macrophages (AM) play pivotal roles in modulating host defense, pulmonary inflammation, and tissue injury following respiratory viral infections. However, the transcriptional regulation of AM function during respiratory viral infections is still largely undefined. Here we have screened the expression of 84 transcription factors in AM in response to influenza A virus (IAV) infection. We found that the transcription factor PPAR-γ was downregulated following IAV infection in AM through type I interferon (IFN)-dependent signaling. PPAR-γ expression in AM was critical for the suppression of exaggerated antiviral and inflammatory responses of AM following IAV and respiratory syncytial virus (RSV) infections. Myeloid PPAR-γ deficiency resulted in enhanced host morbidity and increased pulmonary inflammation following both IAV and RSV infections, suggesting that macrophage PPAR-γ is vital for restricting severe host disease development. Using approaches to selectively deplete recruiting monocytes, we demonstrate that PPAR-γ expression in resident AM is likely important in regulating host disease development. Furthermore, we show that PPAR-γ was critical for the expression of wound healing genes in AM. As such, myeloid PPAR-γ deficiency resulted in impaired inflammation resolution and defective tissue repair following IAV infection. Our data suggest a critical role of PPAR-γ expression in lung macrophages in the modulation of pulmonary inflammation, the development of acute host diseases, and the proper restoration of tissue homeostasis following respiratory viral infections. IMPORTANCE Respiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we identify that PPAR-γ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections. Our data suggest that targeting macrophage PPAR-γ may be a promising therapeutic option in the future to suppress acute inflammation and simultaneously promote recovery from severe diseases associated with respiratory viral infections.

MicroRNA transcriptome analysis of poly I:C-stimulated and PRRSV-infected porcine alveolar macrophages

2019 ◽  
Vol 60 (3-4) ◽  
pp. 375-383 ◽  
Author(s):  
Junjing Wu ◽  
Ziyun Ji ◽  
Mu Qiao ◽  
Xianwen Peng ◽  
Huayu Wu ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Transcriptome Analysis ◽  
Poly I:C

scholarly journals Transcriptome analysis highlights the conserved difference between embryonic and postnatal-derived alveolar macrophages

Blood ◽  
2015 ◽  
Vol 126 (11) ◽  
pp. 1357-1366 ◽  
Author(s):  
Sophie L. Gibbings ◽  
Rajni Goyal ◽  
A. Nicole Desch ◽  
Sonia M. Leach ◽  
Miglena Prabagar ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Transcriptome Analysis ◽  
Key Points ◽  
Embryonic Origin

Key Points Of the 30 000 genes, there are ∼0.1% genes whose expression is linked to the origin of the cell rather than the environment. Marco was most conserved by embryonic origin and not altered by the environment, whereas C1qb and Plbd1 were most conserved by adult origin.

scholarly journals Interferon-Induced Transmembrane Protein 1 Restricts Replication of Viruses That Enter Cells via the Plasma Membrane

2018 ◽  
Vol 93 (6) ◽  
Author(s):  
S. E. Smith ◽  
D. C. Busse ◽  
S. Binter ◽  
S. Weston ◽  
C. Diaz Soria ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Viral Infection ◽  
Viral Infections ◽  
Transmembrane Protein ◽  
Host Susceptibility ◽  
Nucleotide Polymorphisms ◽  
Intracellular Loop ◽  
Antiviral Function ◽  
Syncytial Virus

ABSTRACT The acute antiviral response is mediated by a family of interferon-stimulated genes (ISGs), providing cell-intrinsic immunity. Mutations in genes encoding these proteins are often associated with increased susceptibility to viral infections. One family of ISGs with antiviral function is the interferon-inducible transmembrane proteins (IFITMs), of which IFITM3 has been studied extensively. In contrast, IFITM1 has not been studied in detail. Since IFITM1 can localize to the plasma membrane, we investigated its function with a range of enveloped viruses thought to infect cells by fusion with the plasma membrane. Overexpression of IFITM1 prevented infection by a number of Paramyxoviridae and Pneumoviridae, including respiratory syncytial virus (RSV), mumps virus, and human metapneumovirus (HMPV). IFITM1 also restricted infection with an enveloped DNA virus that can enter via the plasma membrane, herpes simplex virus 1 (HSV-1). To test the importance of plasma membrane localization for IFITM1 function, we identified blocks of amino acids in the conserved intracellular loop (CIL) domain that altered the subcellular localization of the protein and reduced antiviral activity. By screening reported data sets, 12 rare nonsynonymous single nucleotide polymorphisms (SNPs) were identified in human IFITM1, some of which are in the CIL domain. Using an Ifitm1−/− mouse, we show that RSV infection was more severe, thereby extending the range of viruses restricted in vivo by IFITM proteins and suggesting overall that IFITM1 is broadly antiviral and that this antiviral function is associated with cell surface localization. IMPORTANCE Host susceptibility to viral infection is multifactorial, but early control of viruses not previously encountered is predominantly mediated by the interferon-stimulated gene (ISG) family. There are upwards of 300 of these genes, the majority of which do not have a clearly defined function or mechanism of action. The cellular location of these proteins may have an important effect on their function. One ISG located at the plasma membrane is interferon-inducible transmembrane protein 1 (IFITM1). Here we demonstrate that IFITM1 can inhibit infection with a range of viruses that enter via the plasma membrane. Mutant IFITM1 proteins that were unable to localize to the plasma membrane did not restrict viral infection. We also observed for the first time that IFITM1 plays a role in vivo, and Ifitm1−/− mice were more susceptible to viral lung infection. These data contribute to our understanding of how ISGs prevent viral infections.

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