scholarly journals Viral co-infections are associated with dysregulation of HLA family gene expression.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Influenza A ◽  
Microarray Dataset ◽  
Human Coronavirus ◽  
Significant Differential Expression ◽  
A Cell ◽  
Family Gene ◽  
Coronavirus Infection ◽  
Syncytial Virus ◽  
One Year

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.

scholarly journals Differential expression of heterogenous nuclear ribonucleoproteins in viral co-infections.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Differential Expression ◽  
Influenza Season ◽  
Microarray Dataset ◽  
The United States ◽  
Influenza B ◽  
Human Coronavirus ◽  
Significant Differential Expression ◽  
Hnrnp K ◽  
Syncytial Virus ◽  
One Year

Co-infection is a phenomena by which a host or cell is infected by at least two pathogens (1, 2). The severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, has resulted in the death of greater than 200,000 people in the United States in less than one year, with an impending influenza season, raising the prospect of co-infection-related complications (3, 4, 5). We mined a published microarray dataset (6) to discover genes associated with viral co-infection in the blood of human patients, including co-infections involving human rhinovirus, enterovirus, respiratory syncytial virus A, human coronavirus HKU1 and influenza B. We found significant differential expression of heterogenous nuclear ribonucleoproteins including hnRNP K in the blood of patients with viral co-infections. These data suggest hnRNPs may be of relevance to immunity against viral co-infections or utilized by viruses during completion of the viral life cycle in the context of co-infection.

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
Keyword(s):  
Gene Expression ◽  
Influenza A ◽  
Differentially Expressed ◽  
Human Coronavirus ◽  
Gene Encoding ◽  
Non Coding Rna ◽  
Different Types ◽  
Family Gene ◽  
Human Coronaviruses ◽  
One Year

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.

scholarly journals Interleukin-16 is differentially expressed in viral co-infections.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Microarray Data ◽  
Influenza A ◽  
Influenza Season ◽  
Differentially Expressed ◽  
Human Coronavirus ◽  
One Year ◽  
Human Coronavirus 229E

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.

scholarly journals Metagenomic Sequencing To Detect Respiratory Viruses in Persons under Investigation for COVID-19

2020 ◽  
Vol 59 (1) ◽  
pp. e02142-20
Author(s):  
Ahmed Babiker ◽  
Heath L. Bradley ◽  
Victoria D. Stittleburg ◽  
Jessica M. Ingersoll ◽  
Autum Key ◽  
...  
Keyword(s):  
Influenza A ◽  
Viral Infections ◽  
Respiratory Viruses ◽  
Human Metapneumovirus ◽  
Molecular Testing ◽  
Metagenomic Sequencing ◽  
Rt Pcr ◽  
Human Coronavirus ◽  
Testing Algorithms ◽  
Syncytial Virus

ABSTRACTBroad testing for respiratory viruses among persons under investigation (PUIs) for SARS-CoV-2 has been performed inconsistently, limiting our understanding of alternative viral infections and coinfections in these patients. RNA metagenomic next-generation sequencing (mNGS) offers an agnostic tool for the detection of both SARS-CoV-2 and other RNA respiratory viruses in PUIs. Here, we used RNA mNGS to assess the frequencies of alternative viral infections in SARS-CoV-2 RT-PCR-negative PUIs (n = 30) and viral coinfections in SARS-CoV-2 RT-PCR-positive PUIs (n = 45). mNGS identified all viruses detected by routine clinical testing (influenza A [n = 3], human metapneumovirus [n = 2], and human coronavirus OC43 [n = 2], and human coronavirus HKU1 [n = 1]). mNGS also identified both coinfections (1, 2.2%) and alternative viral infections (4, 13.3%) that were not detected by routine clinical workup (respiratory syncytial virus [n = 3], human metapneumovirus [n = 1], and human coronavirus NL63 [n = 1]). Among SARS-CoV-2 RT-PCR-positive PUIs, lower cycle threshold (CT) values correlated with greater SARS-CoV-2 read recovery by mNGS (R2, 0.65; P < 0.001). Our results suggest that current broad-spectrum molecular testing algorithms identify most respiratory viral infections among SARS-CoV-2 PUIs, when available and implemented consistently.

scholarly journals A comparison of influenza and respiratory syncytial virus infections among infants admitted to hospital with acute respiratory infections

1976 ◽  
Vol 77 (3) ◽  
pp. 383-392 ◽  
Author(s):  
E. O. Caul ◽  
D. K. Waller ◽  
S. K. R. Clarke ◽  
B. D. Corner
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Rural Areas ◽  
Influenza A ◽  
Respiratory Infections ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
Syncytial Virus ◽  
One Year

SUMMARYAmong 741 children under 5 years admitted to hospital with respiratory infections during two winters, infection with influenza A virus was diagnosed in 70 (9%), with influenza B virus in 8 (1%), and with respiratory syncytial virus (RSV) in 259 (35 %). Both influenza virus and RSV infections were diagnosed most frequently in children under the age of one year, and diagnosed more frequently in males than females. Influenza illnesses were more severe in boys than girls. Both infections occurred more often, but were not more severe, in children from a conurbation than in those from ‘rural’ areas. Convulsions were the cause of 36% of admissions with influenza A infections, but were rare in RSV infections. Bronchiolitis was the reason for 39% of admissions with RSV infections, but was rare in influenza infections. It is suggested that infants admitted to hospital are a good source of influenza virus strains for monitoring arttigenic variation.

scholarly journals Influenza Viral Infection is a High-Risk Factor for Developing Coronavirus Disease 2019 (COVID-19)

2020 ◽  
Author(s):  
Lei Zhang ◽  
Youwei Zhang
Keyword(s):  
Gene Expression ◽  
Risk Factor ◽  
High Risk ◽  
Viral Infection ◽  
Respiratory System ◽  
Influenza A ◽  
Target Cells ◽  
High Risk Factor ◽  
Syncytial Virus ◽  
Influenza Viral Infection

Coronavirus disease 2019 (COVID-19) is caused by infection with the 2019 novel coronavirus 2 (2019-nCoV, now referred to as SARS-CoV-2). COVID-19 has become a global pandemic since its outbreak at the end of Dec 2019. COVID-19 could lead to severe acute respiratory disease, especially to those who have reduced immunity. Binding of the viral Spike protein (S) to its receptor ACE2 (Angiotensin Converting Enzyme 2) on the surface of target cells has been proven to be key for virus entry and infection. Although ACE2 expression in the respiratory system is necessary for pneumonia infection by SARS-CoV-2, the regulation of ACE2 gene expression remains poorly investigated, especially for patients that are in pre-pathological conditions. Here, by analyzing The Gene Expression Omnibus (GEO) database, we investigated the expression regulation of ACE2 in various kinds of primary epithelial cells from the respiratory system after influenza A or respiratory Syncytial Virus (RSV) infection. Our analyses reveal that infection of influenza A, RSV or influenza vaccines greatly increased ACE2 expression, suggesting that influenza viral infection could represent a high risk factor for developing COVID-19. We also found that the regulatory effect of influenza A virus on ACE2 expression is associated with activation of the interferon beta-induced pathway and viral RNA-activated host response. Together, our data provide a theoretical framework for clinical classification for SARS-CoV-2 infection susceptibility and could be used for future prevention and therapy treatment for COVID-19.

scholarly journals COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve out- come in severe cases

2020 ◽  
Author(s):  
Sorin Draghici ◽  
Tuan-Minh Nguyen ◽  
Larry A. Sonna ◽  
Cordelia Ziraldo ◽  
Radu Vanciu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Influenza A ◽  
Immune Modulation ◽  
Clinical Results ◽  
Current Management ◽  
All Cause Mortality ◽  
Syncytial Virus ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Disease Pathways

Abstract Current management efforts of COVID-19 include: early diagnosis, use of antivirals, and immune modulation. After the initial viral phase of the illness, identification of the patients developing cytokine storm syndrome is critical.1, 2 Treatment of hyper- inflammation in these patients using existing, approved therapies with proven safety profiles could address the immediate need to reduce the rising mortality.3 The identification of existing drugs that could modulate the immune response is an immediate need. Here we show that an analysis of the changes in the gene expression, path- ways and putative mechanisms between SARS-CoV2, influenza A, and respiratory syncytial virus can be used to identify FDA-approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. An important finding is that drugs in the same class may not achieve similar effects. An independent clinical study evaluated 213 subjects, 81 (38%) and 132 (62%) in pre-and post-methylprednisolone groups, respectively. Thirty-day all-cause mortality occurred at a significantly lower rate in the post-methylprednisolone group compared to pre-methylprednisolone group (29.6% vs. 16.6%, p=0.027). Clinical results con- firmed the in silico prediction that methylprednisolone could improve outcomes in severe cases of COVID-19. These findings are important for any future pandemic regardless of the virus.

scholarly journals The phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase, PAICS, is differentially expressed following infection by the coronavirus family.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Transcriptional Repression ◽  
De Novo ◽  
Human Cells ◽  
Human Coronavirus ◽  
Significant Differential Expression ◽  
Purine Synthesis ◽  
Transcriptional Modulation ◽  
Coronavirus Infection ◽  
Microarray Datasets

We mined published and public microarray datasets (1-6) to discover conserved host cell machinery transcriptionally modulated by the coronavirus family. We found significant differential expression and transcriptional repression of a gene utilized during de novo purine synthesis, PAICS, following infection of human cells with the Middle East Respiratory Syndrome (MERS) coronavirus in vitro, in the lungs of mice following infection with the Severe Acute Respiratory Syndrome (SARS) coronavirus 1 (SARS-CoV-1), in the blood and lungs of ferrets following intranasal infection with SARS-CoV-1, but not in human cells infected with the human coronavirus HCoV-229E. These data indicate transcriptional modulation of de novo purine synthesis pathways by viruses of the coronavirus family or during coronavirus infection.

scholarly journals The Establishment of Bortezomib Resistant Myeloma Cell Line KM3/BTZ and Explore the Resistance Mechanism

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5226-5226 ◽  
Author(s):  
Luqun Wang ◽  
Qiong Liu ◽  
Hao Li ◽  
Li Lizhen ◽  
Xin Wang
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Cell Line ◽  
Resistance Index ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Rt Pcr ◽  
A Cell ◽  
Family Gene ◽  
Mdr 1

Abstract Background: Multiple myeloma (MM) is an incurable B-cell malignancy resulting in significant morbidity and mortality, the incidence of second place in hematological malignancies. The proteasome inhibitor bortezomib inhibits IkappaB degradation, prevents NF-kappaB activation, and induces apoptosis in MM cells, has become first-line drug to MM. Despite its promising activity in traditional chemoresistant myeloma patients, however, some patients are resistant or become refractory to bortezomib. Chauhan D et al reported that Blockade of Hsp27 overcomes bortezomib resistance in lymphoma cells (Chauhan D et al., Cancer Re, 2003). However, bortezomib resistance mechanisms in MM remain controversial, the molecular basis of this reduced responsiveness is currently not fully understood. Objective: To establish a bortezomib-resistant cell line KM3 /BTZ of MM, then search for genes related to bortezomib resistance phenotype by analyzing the differential gene expression patterns with cDNA microarray,and explain the mechanism of bortezomib-resistant multiple myeloma. Methods: Bortezomib-resistant KM3/BTZ cell line was generated by increasing concentration of bortezomib to induce KM3 cells in vitro. MTT assay was employed to detect the cytotoxic effect on KM3 and KM3/BTZ cells. The cells apoptosis were analyzed by flow cytometry. We detect the gene expression profile changes between KM3/BTZ and its parent cell line KM3 cells by CDNA microarray. Combining of molecular annotation system MAS3.0 software and detailed analysis of documented resistance genes were used to analyze the data. Specific differentially-expressed genes were chosen for further verification using real-time RT-PCR. The expression of multi-drug resistance 1(MDR-1) gene mRNA was determined by RT-PCR. Results: The KM3/BTZ cell line was established successfully. Bortezomib resistance index values were significantly higher in KM3/BTZ (IC50 =351.2±3.51ng /ml) when compared to KM3 cells (IC50 = 17.8±1.03ng /ml),and the resistance index is 19.7 (P< 0.05). Through gene expression profiling filtering, compared with KM3,770 significantly differently expressed genes were screened out in the KM3/BTZ cell line, of which up and down regulated genes were 287 and 383 respectively, in which heat shock protein family gene HSPB2 was significantly up-regulated (Ratio=14.7455). Downregulated gene list in KM3/BTZ cell line included transcriptional regulators like ZNF family proteins (Tab 1). Upregulated genes in KM3/BTZ cell line included signal transduction related genes like MS4A family protein (Tab 1) also transcriptional regulators like ZNF family proteins (Tab 1). The expression trend of eight genes for further verification was almost consistent with the microarray, excepting gene of JUN (Fig 1). The expression of MDR-1 mRNA was not observed in either resistant or parental cells (Fig 2). Conclusion: We have successfully established bortezomib-resistant cell line KM3/BTZ. MDR-1 was not involved in bortezomib-resistant multiple myeloma cells.HSPB2, ZNF and MS4A family genes are probably related to bortezomib resistance in KM3/BTZ cells. Our results suggest that they may be new targets to overcome resistance to bortezomib in patients with MM. Table 1. ZNF and MS4A family gene expression in KM3/BTZ and KM3 cells Gene B signal* B detection* A signal* A detection* BvsA signal log ratio* BvsA change* ZNF711 85.08 P 206.16 P 0.41269 D ZNF92 6.75 P 14.57 P 0.46328 D ZNF704 10.7 A 26.78 P 0.39955 D ZNF492 7.08 P 3.48 P 2.03448 I ZNF532 87.93 P 43.54 A 2.01952 I ZNF594 10.25 P 4.63 P 2.21382 I ZNF789 269.79 P 97.3 P 2.77276 I ZNF506 330.36 P 149.48 P 2.21006 I MS4A3 1721.58 P 145.3 P 11.84845 I MS4A4A 2688.23 P 100.8 P 26.66895 I MS4A6A 141.96 P 56.47 M 2.513901 I MS4A1 49.02 P 53.11 P 0.92299 NC P: High expression; A: Low expression; M:Marginally D: Decrease; I: Increase; NC: No change *: A:KM3; B: KM3/BTZ Figure 1 Figure 1. Correlations of gene expression changes between oligonueleotide Microarray and qRT-PCR, showing change of selected gene in KM3/BTZ compared with KM3.The Y-axis indicates the log2 transformed ratio of mRNA expression. Figure 2 Figure 2. The expression level of MDR-1 mRNA in KM3 and KM3/BTZ and K562/A cell lines. M: DNA Marker; 1-2: K562/A cell line; 3-4: KM3cell line; 5-6: KM3/BTZ cell line Disclosures No relevant conflicts of interest to declare.

scholarly journals COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve outcome in severe cases

2020 ◽  
Author(s):  
Sorin Draghici ◽  
Tuan-Minh Nguyen ◽  
Larry A Sonna ◽  
Cordelia Ziraldo ◽  
Radu L Vanciu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Influenza A ◽  
Immune Modulation ◽  
Composite Endpoint ◽  
Clinical Results ◽  
Methyl Prednisolone ◽  
Expression Pathways ◽  
Syncytial Virus ◽  
Using Data ◽  
Approved Drugs

Background. Current management efforts of COVID-19 include: early diagnosis, use of antivirals and immune modulation. After the initial viral phase of the illness, identification of the patients developing cytokine storm syndrome is critical. Treatment of this hyper-inflammation in these patients using existing, approved therapies with proven safety profiles could address the immediate need to reduce the rising mortality. Methods. Using data from an A549 cell line, primary human bronchial epithelial (NBHE), as well as from COVID-19-infected lung, we compare the changes in the gene expression, pathways and mechanisms between SARS-CoV2, influenza A, and respiratory syncytial virus. Results. We identified FDA-approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. An important finding is that drugs in the same class will not achieve similar effects. For instance methylprednisolone and prednisolone were predicted to be effective in reverting many of the changes triggered by COVID-19, while other closely related steroids, such as prednisone or dexamethasone, were not. An independent clinical study evaluated 213 subjects, 81 (38%) and 132 (62%) in pre-and post-methylprednisolone groups, respectively. The composite end point was composed of escalation to intensive care units, need for mechanical ventilation, and death. The composite endpoint occurred at a significantly lower rate in post-methylprednisolone group compared to pre-methylprednisolone group (34.9% vs. 54.3%, p=0.005). Conclusion. Clinical results confirmed the efficacy of the in silico prediction that indicated methyl- prednisolone could improve outcomes in severe COVID-19. These findings are important for any future pandemic regardless of the virus.

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