scholarly journals The Novel Early Region 3 Protein E3/49K Is Specifically Expressed by Adenoviruses of Subgenus D: Implications for Epidemic Keratoconjunctivitis and Adenovirus Evolution

Virology ◽  
2002 ◽  
Vol 296 (1) ◽  
pp. 94-106 ◽  
Author(s):  
Jürgen H. Blusch ◽  
François Deryckere ◽  
Mark Windheim ◽  
Zsolt Ruzsics ◽  
Niklas Arnberg ◽  
...  
Keyword(s):  
The Novel ◽  
Epidemic Keratoconjunctivitis ◽  
Early Region ◽  
Early Region 3

scholarly journals Adenovirus Modulates Toll-Like Receptor 4 Signaling by Reprogramming ORP1L-VAP Protein Contacts for Cholesterol Transport from Endosomes to the Endoplasmic Reticulum

2017 ◽  
Vol 91 (6) ◽  
Author(s):  
Nicholas L. Cianciola ◽  
Stacey Chung ◽  
Danny Manor ◽  
Cathleen R. Carlin
Keyword(s):  
Innate Immunity ◽  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
Lipid Droplets ◽  
Cholesterol Transport ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Human Adenoviruses ◽  
Early Region ◽  
Early Region 3

ABSTRACT Human adenoviruses (Ads) generally cause mild self-limiting infections but can lead to serious disease and even be fatal in high-risk individuals, underscoring the importance of understanding how the virus counteracts host defense mechanisms. This study had two goals. First, we wished to determine the molecular basis of cholesterol homeostatic responses induced by the early region 3 membrane protein RIDα via its direct interaction with the sterol-binding protein ORP1L, a member of the evolutionarily conserved family of oxysterol-binding protein (OSBP)-related proteins (ORPs). Second, we wished to determine how this interaction regulates innate immunity to adenovirus. ORP1L is known to form highly dynamic contacts with endoplasmic reticulum-resident VAP proteins that regulate late endosome function under regulation of Rab7-GTP. Our studies have demonstrated that ORP1L-VAP complexes also support transport of LDL-derived cholesterol from endosomes to the endoplasmic reticulum, where it was converted to cholesteryl esters stored in lipid droplets when ORP1L was bound to RIDα. The virally induced mechanism counteracted defects in the predominant cholesterol transport pathway regulated by the late endosomal membrane protein Niemann-Pick disease type C protein 1 (NPC1) arising during early stages of viral infection. However, unlike NPC1, RIDα did not reconstitute transport to endoplasmic reticulum pools that regulate SREBP transcription factors. RIDα-induced lipid trafficking also attenuated proinflammatory signaling by Toll-like receptor 4, which has a central role in Ad pathogenesis and is known to be tightly regulated by cholesterol-rich “lipid rafts.” Collectively, these data show that RIDα utilizes ORP1L in a way that is distinct from its normal function in uninfected cells to fine-tune lipid raft cholesterol that regulates innate immunity to adenovirus in endosomes. IMPORTANCE Early region 3 proteins encoded by human adenoviruses that attenuate immune-mediated pathology have been a particularly rich source of information regarding intracellular protein trafficking. Our studies with the early region 3-encoded RIDα protein also provided fundamental new information regarding mechanisms of nonvesicular lipid transport and the flow of molecular information at membrane contacts between different organelles. We describe a new pathway that delivers cholesterol from endosomes to the endoplasmic reticulum, where it is esterified and stored in lipid droplets. Although lipid droplets are attracting renewed interest from the standpoint of normal physiology and human diseases, including those resulting from viral infections, experimental model systems for evaluating how and why they accumulate are still limited. Our studies also revealed an intriguing relationship between lipid droplets and innate immunity that may represent a new paradigm for viruses utilizing these organelles.

scholarly journals Effect of Transgene Location, Transcriptional Control Elements and Transgene Features in Armed Oncolytic Adenoviruses

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1034 ◽  
Author(s):  
Martí Farrera-Sal ◽  
Cristina Fillat ◽  
Ramon Alemany
Keyword(s):  
Transcriptional Control ◽  
Recombinant Adenovirus ◽  
Clinical Results ◽  
Early Region ◽  
Oncolytic Adenoviruses ◽  
Limited Efficacy ◽  
Insertion Sites ◽  
Early Region 3 ◽  
Virus Fitness ◽  
Transgene Insertion

Clinical results with oncolytic adenoviruses (OAds) used as antitumor monotherapies show limited efficacy. To increase OAd potency, transgenes have been inserted into their genome, a strategy known as “arming OAds”. Here, we review different parameters that affect the outcome of armed OAds. Recombinant adenovirus used in gene therapy and vaccination have been the basis for the design of armed OAds. Hence, early region 1 (E1) and early region 3 (E3) have been the most commonly used transgene insertion sites, along with partially or complete E3 deletions. Besides transgene location and orientation, transcriptional control elements, transgene function, either virocentric or immunocentric, and even the codons encoding it, greatly impact on transgene levels and virus fitness.

scholarly journals Adenovirus Early Region 3 Transgenes Expressed in β Cells Prevent Autoimmune Diabetes in Nonobese Diabetic Mice: Effects of Deleting the Adenovirus Death Protein 11.6K

2005 ◽  
Vol 79 (1) ◽  
pp. 619-621 ◽  
Author(s):  
Melissa A. Pierce ◽  
Anton Svetlanov ◽  
Marshall S. Horwitz ◽  
David V. Serreze
Keyword(s):  
Autoimmune Diabetes ◽  
Gene Cassette ◽  
Diabetic Mice ◽  
Β Cells ◽  
Early Region ◽  
Nonobese Diabetic ◽  
Proapoptotic Protein ◽  
Nonobese Diabetic Mice ◽  
Early Region 3

ABSTRACT The incidence of type 1 diabetes (T1D) is decreased in nonobese diabetic mice expressing the complete cassette of adenovirus early region 3 (E3) immunomodulating genes in pancreatic β cells. Embedded among the antiapoptotic E3 genes is one encoding an adenovirus death protein (ADP), which contributes to release of virion particles by promoting cell lysis. Because removal of this proapoptotic protein might have further enhanced the ability of E3 proteins to prevent T1D, an ADP-inactivated E3 construct was tested. Significantly, deletion of ADP did not improve the diabetes-protective effect of an E3 gene cassette.

scholarly journals Epidemic Keratoconjunctivitis Due to the Novel Hexon-Chimeric-Intermediate 22,37/H8 Human Adenovirus

2008 ◽  
Vol 46 (10) ◽  
pp. 3259-3269 ◽  
Author(s):  
K. Aoki ◽  
H. Ishiko ◽  
T. Konno ◽  
Y. Shimada ◽  
A. Hayashi ◽  
...  
Keyword(s):  
Human Adenovirus ◽  
The Novel ◽  
Epidemic Keratoconjunctivitis

scholarly journals Subgroup B Adenovirus Type 35 Early Region 3 mRNAs Differ from Those of the Subgroup C Adenoviruses

Virology ◽  
1996 ◽  
Vol 215 (2) ◽  
pp. 165-177 ◽  
Author(s):  
CHRISTOPHER F. BASLER ◽  
MARSHALL S. HORWITZ
Keyword(s):  
Adenovirus Type ◽  
Early Region ◽  
Early Region 3

scholarly journals Sequence and genetic organization of adenovirus type 35 early region 3.

1988 ◽  
Vol 62 (11) ◽  
pp. 4431-4437 ◽  
Author(s):  
P R Flomenberg ◽  
M Chen ◽  
M S Horwitz
Keyword(s):  
Adenovirus Type ◽  
Genetic Organization ◽  
Early Region ◽  
Early Region 3

scholarly journals The role of human adenovirus early region 3 proteins (gp19K, 10.4K, 14.5K, and 14.7K) in a murine pneumonia model.

1996 ◽  
Vol 70 (4) ◽  
pp. 2431-2439 ◽  
Author(s):  
T E Sparer ◽  
R A Tripp ◽  
D L Dillehay ◽  
T W Hermiston ◽  
W S Wold ◽  
...  
Keyword(s):  
Human Adenovirus ◽  
Early Region ◽  
Early Region 3

scholarly journals Analysis of early region 3 mutants of mouse adenovirus type 1.

1996 ◽  
Vol 70 (9) ◽  
pp. 5867-5874 ◽  
Author(s):  
C W Beard ◽  
K R Spindler
Keyword(s):  
Adenovirus Type ◽  
Early Region ◽  
Early Region 3

scholarly journals Adenovirus Early Region 3 Antiapoptotic 10.4K, 14.5K, and 14.7K Genes Decrease the Incidence of Autoimmune Diabetes in NOD Mice

Diabetes ◽  
2003 ◽  
Vol 52 (5) ◽  
pp. 1119-1127 ◽  
Author(s):  
M. A. Pierce ◽  
H. D. Chapman ◽  
C. M. Post ◽  
A. Svetlanov ◽  
S. Efrat ◽  
...  
Keyword(s):  
Autoimmune Diabetes ◽  
Nod Mice ◽  
Early Region ◽  
Early Region 3
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