BioProject: The University of Texas Medical Branch, Galveston

  Source:		PRJNA118845
  Download:	https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17400

     		Dynamic Innate Immune Responses of Human
			Bronchial Epithelial Cells against SARS-CoV
			and DOHV infection

			The University of Texas Medical Branch, Galveston
			(Owner) [website] [twitter video]

			Severe acute respiratory syndrome-associated
			coronavirus (SARS-CoV) infection causes an
			immune-mediated disease. We have recently
			shown that SARS-CoV-induced epithelial
			Calu-3 cytokines could exacerbate and
			dampen host inflammatory and T cell
			responses, respectively, through modulating
			the functions of macrophages and dendritic
			cells, thereby suggesting that not only are
			lung epithelial cells the primary cells of
			SARS-CoV infection, but they also involve
			in initiating and orchestrating the host innate
			and adaptive immunity. Comprehensive
			evaluation of the complex epithelial signaling
			to SARS-CoV is, thus, crucial for paving the
			way to better understand SARS pathogenesis
			and develop the innovative therapeutics against
			SARS. Here, based on the microarray-based
			functional genomics, we reported that 2B4
			cells, a clonal derivative of Calu-3 cells,
			elicited a temporal and spatial activation
			of nuclear factor (NF)kappaB, activator
			protein (AP)-1 (ATF2/c-Jun), and
			interferon regulatory factor (IRF)-3/-7 at 12-,
			24-, and 48-hrs post infection (p.i.), respectively,
			resulting in the activation of many antiviral genes,
			including interferon (IFN)-β, -λs, SARS-related
			inflammatory mediators, and various IFN-stimulated
			genes (ISGs). While elevated responses of
			IFN-β and IFN-λs were not detected until
			48-hrs p.i., as a consequence of a delayed
			IRF-3/-7 activation, we showed, for the
			first time, that both types of IFNs exerted
			previously under-described non-redundant,
			complementary, and/or synergistic effects
			on the epithelial defense against SARS-CoV.
			Collectively, our results highlight the molecular
			mechanisms of the sequential activation
			of virus- and IFN-dependent signaling of
			lung epithelial cells against SARS-CoV and
			identify novel cellular targets for future studies,
			aiming at advancing strategies against SARS.
			Overall design: DNA microarrays were performed
			in the Molecular Genomics (MG) Core Facilities ⇗
			at UTMB. The detailed information about the
			procedures of microarray analysis has been
			posted on the MG Core Facilities website
			(genomics@scms.utmb.edu). To characterize
			the dynamic, spatial, and temporal changes
			of the gene expression induced by SARS-CoV,
			confluent 2B4 cells grown in T-75 flasks
			were infected with SARS-CoV (MOI=0.1) or
			remained uninfected (as control) for 12,
			24, and 48hrs. Because 2B4 cells were also
			permissive to the productive infection of
			Dhori virus (DHOV), a member of the Orthomyxoviridae
			family within the Thogotovirus genus, resulting
			in robust responses of IFNs and other
			pro-inflammatory mediators, we also established
			parallel cultures of DHOV-infected 2B4 cells
			(MOI=0.1) for the comparative analysis of
			global gene expression elicited by SARS-CoV-
			versus DHOV-infected 2B4 cells. To meet
			the minimal number required for application
			of statistical algorithms, we performed
			the study in triplicate at each time point
			for mock-, SARS-CoV-, and DHOV-infected
			cultures, yielding a total of 27 arrays.
			Briefly, supernatants were harvested from
			differentially treated cultures at 12-, 24-,
			and 48-hrs p.i. for subsequent analyses
			of viral yields and cytokine profiling,
			whereas the cells were subjected to total
			RNA extraction by using an RNAqueous-4PCR
			kit and following the protocol recommended
			by the manufacturer (Ambion, Austin, TX ⇗).
			Purified RNA samples were sent to our core
			facility for conversion to cDNA, biotin-labeled,
			and hybridized to 27 Affymetrix Human Genome
			U133 Plus 2.0 “Gene Chips” each of which
			contained 54,675 probe set identifiers representing
			more than ~47,400 transcripts that identify
			~38,500 well-characterized genes, and various
			internal controls (Affymetrix, Santa Clara, CA ⇗).
			Mock-infected cells were compared to cells
			infected with SARS-CoV or DHOV at each time


			20090954 Dynamic innate immune responses
			of human bronchial epithelial cells to
			severe acute respiratory syndrome-associated
			coronavirus infection.

			19380580 Severe acute respiratory syndrome
			coronavirus M protein inhibits type I interferon
			production by impeding the formation of
			TRAF3.TANK.TBK1/IKKepsilon complex.

			19297479 Differential virological and immunological
			outcome of severe acute respiratory syndrome
			coronavirus infection in susceptible and
			resistant transgenic mice expressing human
			angiotensin-converting enzyme 2.

			19004938 Severe acute respiratory syndrome
			(SARS) coronavirus-induced lung epithelial
			cytokines exacerbate SARS pathogenesis by
			modulating intrinsic functions of monocyte-derived
			macrophages and dendritic cells.

			18448662 The discovery of
			angiotensin-converting enzyme 2
			and its role in acute lung injury in mice.

			18385368 Dhori virus (Orthomyxoviridae:
			Thogotovirus) infection of mice produces a
			disease and cytokine response pattern similar
			to that of highly virulent influenza A (H5N1) virus
			infection in humans.

			18305050 Severe acute respiratory syndrome
			coronavirus nsp1 suppresses host gene expression,
			including that of type I interferon, in infected

			17715225 Severe acute respiratory syndrome
			coronavirus evades antiviral signaling: role of nsp1
			and rational design of an attenuated strain.

			17696609 Functional genomics highlights
			differential induction of antiviral pathways in the lungs
			of SARS-CoV-infected macaques.

			17596301 Severe acute respiratory syndrome
			coronavirus ORF6 antagonizes STAT1 function by
			sequestering nuclear import factors on the rough
			endoplasmic reticulum/Golgi membrane.

			17426188 Dhori virus (Orthomyxoviridae:
			Thogotovirus) infection in mice: a model of the
			pathogenesis of severe orthomyxovirus infection.

			17316733 Group 2 coronaviruses prevent
			immediate early interferon induction by
			protection of viral RNA from host cell

			17204473 Viral infections activate types I and III
			interferon genes through a common mechanism.

			17176632 Evaluation of immunomodulators,
			interferons and known in vitro SARS-coV
			inhibitors for inhibition of SARS-coV replication
			in BALB/c mice.

			17108024 Severe acute respiratory syndrome
			coronavirus open reading frame (ORF) 3b, ORF 6,
			and nucleocapsid proteins function as interferon

			17108019 Severe acute respiratory syndrome
			coronavirus infection of mice transgenic for the human
			Angiotensin-converting enzyme 2 virus receptor.

			17079305 Mouse hepatitis virus does not induce
			Beta interferon synthesis and does not inhibit
			its induction by double-stranded RNA.

			16912115 Severe acute respiratory syndrome
			coronavirus nsp1 protein suppresses host gene
			expression by promoting host mRNA degradation.

			16753195 Innate immune responses: crosstalk of
			signaling and regulation of gene transcription. 

			16571117 Inhibition of cytokine gene expression and
			induction of chemokine genes in non-lymphatic cells
			infected with SARS coronavirus.

			16474426 Antiviral innate immunity pathways.

			16379499 Time course and cellular localization of
			SARS-CoV nucleoprotein and RNA in lungs from
			fatal cases of SARS.

			16306622 Severe acute respiratory syndrome
			coronavirus infection of human ciliated airway
			epithelia: role of ciliated cells in viral spread in
			the conducting airways of the lungs.

			16282461 ACE2 receptor expression and
			severe acute respiratory syndrome
			coronavirus infection depend on differentiation
			of human airway epithelia.

			16195357 Early enhanced expression of
			interferon-inducible protein-10 (CXCL-10)
			and other chemokines predicts adverse outcome
			in severe acute respiratory syndrome.

			16014910 Apical entry and release of
			severe acute respiratory syndrome-associated
			coronavirus in polarized Calu-3 lung epithelial cells.

			15919935 Cytokine responses in
			severe acute respiratory syndrome
			coronavirus-infected macrophages in vitro:
			possible relevance to pathogenesis.

			15858003 Comparative host gene transcription by
			microarray analysis early after infection of the Huh7
			cell line by severe acute respiratory syndrome
			coronavirus and human coronavirus 229E.

			15777647 Microarray and real-time RT-PCR analyses
			of differential human gene expression patterns
			induced by severe acute respiratory syndrome
			(SARS) coronavirus infection of Vero cells.

			15681410 Inhibition of Beta interferon induction
			by severe acute respiratory syndrome coronavirus
			suggests a two-step model for activation of
			interferon regulatory factor 3.

			15657466 Characterization of cytokine/chemokine
			profiles of severe acute respiratory syndrome.

			15655079 Expression profile of immune
			response genes in patients with
			Severe Acute Respiratory Syndrome.

			15607755 Ribavirin and interferon-beta
			synergistically inhibit SARS-associated coronavirus
			replication in animal and human cell lines.

			15602737 An interferon-gamma-related
			cytokine storm in SARS patients.

			15357874 A human in vitro model system for
			investigating genome-wide host responses to
			SARS coronavirus infection.

			15356152 Mechanisms of host defense following
			severe acute respiratory syndrome-coronavirus
			(SARS-CoV) pulmonary infection of mice.

			15316659 Infection of cultured intestinal epithelial
			cells with severe acute respiratory syndrome

			15296649 Potent inhibition of SARS-associated
			coronavirus (SCOV) infection and replication by
			type I interferons (IFN-alpha/beta) but not by
			type II interferon (IFN-gamma).

			15272286 Pulmonary pathology of
			severe acute respiratory syndrome
			in Toronto.

			15271897 Analysis of serum cytokines in
			patients with severe acute respiratory syndrome.

			15030704 Interferon-beta 1a and SARS
			coronavirus replication.

			14981511 Pegylated interferon-alpha protects type
			1 pneumocytes against SARS coronavirus infection
			in macaques.

			14743497 Tissue and cellular tropism of
			the coronavirus associated with
			severe acute respiratory syndrome:
			an in-situ hybridization study of fatal cases.

			12890365 Pathological study on
			severe acute respiratory syndrome.

			12816821 Haematological manifestations in
			patients with severe acute respiratory syndrome:
			retrospective analysis.

			12781536 Lung pathology of fatal
			severe acute respiratory syndrome.

			12730500 Characterization of a novel
			coronavirus associated with
			severe acute respiratory syndrome.

			12711465 Coronavirus as a possible cause of
			severe acute respiratory syndrome.

			12690092 A novel coronavirus associated with
			severe acute respiratory syndrome.

			12690091 Identification of a novel coronavirus in
			patients with severe acute respiratory syndrome.

			12039028 Signaling through the JAK/STAT pathway,
			recent advances and future challenges.

			11951031 Decoding the patterns of self and nonself
			by the innate immune system.

			10837071 Phosphorylation meets ubiquitination:
			the control of NF-[kappa]B activity.

			9867498 Epithelia cells as regulators of airway

			9311517 Airway epithelium as an effector of
			inflammation: molecular regulation of secondary

			8548797 Virus induction of human IFN beta gene
			expression requires the assembly of an

			7692897 Reverse transcription-polymerase chain
			reaction (RT-PCR) phenotypic analysis of cell cultures
			of human tracheal epithelium, tracheobronchial
			glands, and lung carcinomas.

			7515578 Calu-3: a human airway epithelial cell line
			that shows cAMP-dependent Cl- secretion.

			2155562 Receptors on airway gland cells.

     		                         Embed       Tweet       Print