scholarly journals The HLA complex non-coding RNA HCG4 is differentially expressed in the blood of patients with coronavirus co-infections.

2020 ◽  
Author(s):  
Shahan Mamoor

The human coronavirus SARS-CoV-2 (1) has resulted in the death of over 200,000 Americans in less than one year (2). Infection of a person already suffering from a viral infection, a phenomena known as co-infection can potentially pose a problem during the upcoming influenza season. We mined published microarray data (3) to identify genes most differentially expressed in the whole blood of patients suffering from human coronavirus co-infections. We found that the gene encoding the HLA complex non-coding RNA HCG4 was among those whose expression changed most significantly transcriptome-wide when comparing the blood of patients suffering from three different types of co-infections: human coronavirus NL63 and rhinovirus, human coronavirus HKU1 and rhinovirus, as well as in human coronavirus OC43 and influenza A co-infection. We previously reported significant transcriptome-wide changes in HLA family gene expression (4), as well as in changes in gene expression of the cathepsins in viral co-infection (5). Together, these data suggest the process of antigen presentation could be altered during viral co-infections involving the human coronaviruses.

2020 ◽  
Author(s):  
Shahan Mamoor

The human coronavirus SARS-CoV-2 (1) has resulted in the death of over 180,000 Americans in less than one year (2). Infection of a person already suffering from a viral infection, a phenomena known as co-infection can potentially pose a problem during the upcoming influenza seasons. We mined published microarray data (3) to identify genes most differentially expressed in the whole blood of patients suffering from human coronavirus co-infections. We found that the gene encoding NQO2 (4) was among those whose expression changed most significantly transcriptome-wide when comparing the blood of patients suffering from three different types of co-infections: human coronavirus NL63 and rhinovirus, human coronavirus HKU1 and rhinovirus, as well as in human coronavirus 229E and influenza A co-infection. NQO2 is reported to have functions in the B-lymphocyte response (5) and could be relevant to the process of viral co-infection involving the human coronavirus family.


2020 ◽  
Author(s):  
Shahan Mamoor

Co-infection is a process by which a cell or organism already infected with a virus is then infected with a second, different virus (1, 2). The human coronavirus SARS-CoV-2 has resulted in the death of nearly 200,000 Americans in less than one year (3, 4); the upcoming influenza could potentially pose a problem with respect to co-infection with Influenza and SARS-CoV-2; significant co-infection in patients with SARS-CoV-2 has been reported (5). We mined a published microarray dataset (6) to discover genes associated with viral co-infection in patients with a coronavirus infection. We found that genes of the HLA family, particularly HLA-DRB and HLA-A, were significantly differentially expressed in the blood of patients with human coronavirus infections, including HCoV-229E, HCoV OC43, HCoV NL63, and HCoV HKU1. Different viral co-infections, including Influenza A, Human Rhinovirus, Enterovirus, and Respiratory Syncytial Virus A co-infections were also associated with significant differential expression of HLA family genes in patient blood. Perturbation of HLA family gene expression appears to be a general feature of viral co-infection in humans.


2020 ◽  
Author(s):  
Shahan Mamoor

The SARS-CoV-2 pandemic has resulted in close to 1,000,000 deaths worldwide in less than one year (1) with an upcoming influenza season, raising the prospect of complications resulting from co-infections. Our understanding of gene expression in patients with viral co-infection is limited. We mined published microarray data (2) to identify transcriptional features most significantly associated with viral co-infection. We identified the cytokine interleukin-16 as among the most differentially expressed genes in the blood of patients with viral co-infections, including in a patient with co-infection of influenza A and human coronavirus OC43 and in a patient with co-infection of influenza A and human coronavirus 229E. Interleukin-16 may be relevant to the biology of viral co-infection.


2020 ◽  
Author(s):  
Shahan Mamoor

The human coronavirus SARS-CoV-2 (1) has resulted in the death of over 200,000 Americans in less than one year (2). Infection of a person already suffering from a viral infection, a phenomena known as co-infection can potentially pose a problem during the upcoming influenza season. We mined published microarray data (3) to identify genes most differentially expressed in the whole blood of patients suffering from viral co-infections, including co-infections involving a human coronavirus. We found that the UVSSA gene, encoding the UV stimulated scaffold protein A, was among the genes whose expression changed most significantly transcriptome-wide when in the blood of four patients suffering from two different types of co-infections: human coronavirus HKU1 and human rhinovirus, as well as in human coronavirus OC43 and influenza A co-infection. UVSSA may be of relevance to biology underlying some viral co-infections.


2022 ◽  
Vol 12 ◽  
Author(s):  
Beatrice E. Gee ◽  
Andrea Pearson ◽  
Iris Buchanan-Perry ◽  
Roger P. Simon ◽  
David R. Archer ◽  
...  

Whole transcriptome RNA-sequencing was performed to quantify RNA expression changes in whole blood samples collected from steady state sickle cell anemia (SCA) and control subjects. Pediatric SCA and control subjects were recruited from Atlanta (GA)—based hospital(s) systems and consented for RNA sequencing. RNA sequencing was performed on an Ion Torrent S5 sequencer, using the Ion Total RNA-seq v2 protocol. Data were aligned to the hg19 reference genome and analyzed in the Partek Genomics studio package (v7.0). 223 genes were differentially expressed between SCA and controls (± 1.5 fold change FDR p < 0.001) and 441 genes show differential transcript expression (± 1.5 fold FDR p < 0.001). Differentially expressed RNA are enriched for hemoglobin associated genes and ubiquitin-proteasome pathway genes. Further analysis shows higher gamma globin gene expression in SCA (33-fold HBG1 and 49-fold HBG2, both FDR p < 0.05), which did not correlate with hemoglobin F protein levels. eQTL analysis identified SNPs in novel non-coding RNA RYR2 gene as having a potential regulatory role in HBG1 and HBG2 expression levels. Gene expression correlation identified JHDM1D-AS1(KDM7A-DT), a non-coding RNA associated with angiogenesis, enhanced GATA1 and decreased JAK-STAT signaling to correlate with HBG1 and HBG2 mRNA levels. These data suggest novel regulatory mechanisms for fetal hemoglobin regulation, which may offer innovative therapeutic approaches for SCA.


2020 ◽  
Vol 94 (18) ◽  
Author(s):  
Xuesen Zhao ◽  
Shuangli Zheng ◽  
Danying Chen ◽  
Mei Zheng ◽  
Xinglin Li ◽  
...  

ABSTRACT C3A is a subclone of the human hepatoblastoma HepG2 cell line with strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection, we found that ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2), gamma-interferon-inducible lysosome/endosome-localized thiolreductase (GILT), and lymphocyte antigen 6 family member E (LY6E), the three cellular proteins identified to function in interference with virus entry, were expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-O43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFN-inducible transmembrane 3 (IFITM3) restriction of human coronavirus (CoV) entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis via a mechanism distinct from other factors that modulate CoV entry. IMPORTANCE Virus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control of host innate and adaptive immune responses. In the last decade, several interferon-inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH, and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as a host factor that facilitates the entry of several human-pathogenic viruses, including human immunodeficiency virus, influenza A virus, and yellow fever virus. Identification of LY6E as a potent restriction factor of coronaviruses expands the biological function of LY6E and sheds new light on the immunopathogenesis of human coronavirus infection.


mSystems ◽  
2016 ◽  
Vol 1 (4) ◽  
Author(s):  
John D. Lippolis ◽  
Brian W. Brunelle ◽  
Timothy A. Reinhardt ◽  
Randy E. Sacco ◽  
Tyler C. Thacker ◽  
...  

ABSTRACT Bacteria can exhibit various types of motility. It is known that different types of motilities can be associated with virulence. In this work, we compare gene expression levels in bacteria that were grown under conditions that promoted three different types of E. coli motility. Better understanding of the mechanisms of how bacteria can cause an infection is an important first step to better diagnostics and therapeutics. Bacterial motility is thought to play an important role in virulence. We have previously shown that proficient bacterial swimming and swarming in vitro is correlated with the persistent intramammary infection phenotype observed in cattle. However, little is known about the gene regulation differences important for different motility phenotypes in Escherichia coli. In this work, three E. coli strains that cause persistent bovine mastitis infections were grown in three media that promote different types of motility (planktonic, swimming, and swarming). Using whole-transcriptome RNA sequencing, we identified a total of 935 genes (~21% of the total genome) that were differentially expressed in comparisons of the various motility-promoting conditions. We found that approximately 7% of the differentially expressed genes were associated with iron regulation. We show that motility assays using iron or iron chelators confirmed the importance of iron regulation to the observed motility phenotypes. Because of the observation that E. coli strains that cause persistent infections are more motile, we contend that better understanding of the genes that are differentially expressed due to the type of motility will yield important information about how bacteria can become established within a host. Elucidating the mechanisms that regulate bacterial motility may provide new approaches in the development of intervention strategies as well as facilitate the discovery of novel diagnostics and therapeutics. IMPORTANCE Bacteria can exhibit various types of motility. It is known that different types of motilities can be associated with virulence. In this work, we compare gene expression levels in bacteria that were grown under conditions that promoted three different types of E. coli motility. Better understanding of the mechanisms of how bacteria can cause an infection is an important first step to better diagnostics and therapeutics.


2008 ◽  
Vol 32 (3) ◽  
pp. 299-310 ◽  
Author(s):  
James A. Lederer ◽  
Bernard H. Brownstein ◽  
M. Cecilia Lopez ◽  
Sandra MacMillan ◽  
Adam J. Delisle ◽  
...  

A primary objective of the large collaborative project entitled “Inflammation and the Host Response to Injury” was to identify leukocyte genes that are differentially expressed after two different types of injury in mouse models and to test the hypothesis that both forms of injury would induce similar changes in gene expression. We report here the genes that are expressed in white blood cells (WBCs) and in splenocytes at 2 h, 1 day, 3 days, and 7 days after burn and sham injury or trauma-hemorrhage (T-H) and sham T-H. Affymetrix Mouse Genome 430 2.0 GeneChips were used to profile gene expression, and the results were analyzed by dCHIP, BRB Array Tools, and Ingenuity Pathway Analysis (IPA) software. We found that the highest number of genes differentially expressed following burn injury were at day 1 for both WBCs (4,989) and for splenocytes (4,715) and at day 1 for WBCs (1,167) and at day 3 for splenocytes (1,117) following T-H. The maximum overlap of genes that were expressed after both forms of injury were at day 1 in WBCs (136 genes) and at day 7 in splenocytes (433 genes). IPA revealed that the cell-to-cell signaling, cell death, immune response, antiapoptosis, and cell cycle control pathways were affected most significantly. In summary, this report provides a database of genes that are modulated in WBCs and splenocytes at sequential time points after burn or T-H in mice and reveals that relatively few leukocyte genes are expressed in common after these two forms of injury.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yifang Liao ◽  
Ping Li ◽  
Yanxia Wang ◽  
Hong Chen ◽  
Shangwei Ning ◽  
...  

Abstract Background Asthma is a heterogeneous disease characterized by chronic airway inflammation. Long non-coding RNA can act as competing endogenous RNA to mRNA, and play significant role in many diseases. However, there is little known about the profiles of long non-coding RNA and the long non-coding RNA related competing endogenous RNA network in asthma. In current study, we aimed to explore the long non-coding RNA-microRNA-mRNA competing endogenous RNA network in asthma and their potential implications for therapy and prognosis. Methods Asthma-related gene expression profiles were downloaded from the Gene Expression Omnibus database, re-annotated with these genes and identified for asthma-associated differentially expressed mRNAs and long non-coding RNAs. The long non-coding RNA-miRNA interaction data and mRNA-miRNA interaction data were downloaded using the starBase database to construct a long non-coding RNA-miRNA-mRNA global competing endogenous RNA network and extract asthma-related differentially expressed competing endogenous RNA network. Finally, functional enrichment analysis and drug repositioning of asthma-associated differentially expressed competing endogenous RNA networks were performed to further identify key long non-coding RNAs and potential therapeutics associated with asthma. Results This study constructed an asthma-associated competing endogenous RNA network, determined 5 key long non-coding RNAs (MALAT1, MIR17HG, CASC2, MAGI2-AS3, DAPK1-IT1) and identified 8 potential new drugs (Tamoxifen, Ruxolitinib, Tretinoin, Quercetin, Dasatinib, Levocarnitine, Niflumic Acid, Glyburide). Conclusions The results suggested that long non-coding RNA played an important role in asthma, and these novel long non-coding RNAs could be potential therapeutic target and prognostic biomarkers. At the same time, potential new drugs for asthma treatment have been discovered through drug repositioning techniques, providing a new direction for the treatment of asthma.


2020 ◽  
Author(s):  
Shahan Mamoor

Parkinson’s Disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra of the basal ganglia (1). We mined published and public microarray datasets (2, 3) to identify genes whose expression was most different in the substantial nigra of patients with PD as compared to that of non-affected patients. We identified significant changes in expression of the gene encoding the long intergenic non-coding RNA LINC00643 in the substantia nigra of patients with PD.


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