The 10,400- and 14,500-dalton proteins encoded by region E3 of adenovirus form a complex and function together to down-regulate the epidermal growth factor receptor

Tollefson, Ann E.; Stewart, A. Renee; Yei, Soonpin; Saha, S. K.; Wold, William S.M.

doi:10.1128/jvi.65.6.3095-3105.1991

Cited by 85 publications

(36 citation statements)

References 45 publications

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“…Species C, which is one of the most studied HAdV, seems to express seven E3 gene products: 12.5K, 6.7K, 19K, 11.6K, receptor internalization and degradation α (RIDα) (formerly 10.4K), RIDβ (formerly 14.5K), and 14.7K . The 19K protein is present in species B, C, D, and E. The 12.5K protein is found in species A to E, while RIDα, RIDβ, and 14.7K proteins are encoded by all species .…”

Section: Adenovirus Transcription Unitsmentioning

confidence: 99%

Immune evasion by adenoviruses: a window into host–virus adaptation

Oliveira

Bouvier

2019

FEBS Letters

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Human adenoviruses (HAdVs) are widespread pathogens that cause a number of partially overlapping, species-specific infections associated with respiratory, urinary, gastrointestinal, and ocular diseases. The early 3 (E3) region of adenoviruses is highly divergent between different species, and it encodes a multitude of proteins with immunomodulatory functions. The study of genetic diversity in the E3 region offers a unique opportunity to gain insight into how the various HAdVs have evolutionarily adapted in response to the selection pressures exerted by host immune defenses. The objective of this review was to discuss subversion of host antiviral immune responses by HAdVs, with a focus on suppression of MHC class I antigen presentation, as a window into host-HAdV adaptation.

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Section: Adenovirus Transcription Unitsmentioning

confidence: 99%

Immune evasion by adenoviruses: a window into host–virus adaptation

Oliveira

Bouvier

2019

FEBS Letters

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“…To counteract this assault, Ad produces the E3 proteins 10.4K (64), 14.5K (63), and 14.7K (66), which prevent cytolysis of virally infected cells by TNF-␣ (28,29). The 10.4K and 14.5K proteins form a complex (29,65) that localizes to the plasma and cytoplasmic membranes (42,43,59), while the 14.7K protein is found in the nuclear and cytoplasmic fractions (62). 14.7K and 10.4K/14.5K function independently and redundantly in preventing TNF-␣ lysis in vitro (28).…”

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confidence: 99%

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

Sparer

Tripp

Dillehay

et al. 1996

J Virol

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Products of human adenovirus (Ad) early region 3 (E3) inhibit both specific (cytotoxic T lymphocytes [CTLs]) and innate (tumor necrosis factor alpha [TNF-␣]) immune responses in vitro. The E3 gp19K protein prevents CTL recognition of Ad-infected fibroblasts by sequestering major histocompatibility complex class I proteins in the endoplasmic reticulum. E3 proteins 10.4K, 14.5K, and 14.7K function to protect infected cells from TNF-␣ cytolysis. To address the in vivo functions of these proteins, Ad mutants that lack the E3 genes encoding these proteins were inoculated intranasally into C57BL/10SnJ (H-2 b) mice. Mutants that lack the gp19K gene failed to alter CTL generation or to affect Ad-induced pulmonary infiltrates. Since gamma interferon (IFN-␥) is capable of overcoming gp19K suppression of CTL lysis in vitro, mice were depleted of IFN-␥ and inoculated with gp19K mutants. Even when IFN-␥ was depleted, gp19K was incapable of altering pulmonary lesions. These results are not in accord with the function of gp19K in vitro and suggest that gp19K does not affect immune recognition in vivo during an acute virus infection, yet they do not exclude the possibility that gp19K blocks immune recognition of Ad during a persistent infection. In contrast, when mice were inoculated with Ad mutants that lack the TNF resistance genes (14.7K and either 10.4K or 14.5K), there was a marked increase in alveolar infiltration and no change in the amounts of perivascular/peribronchiolar infiltration compared with wild-type-Ad-induced pathology. These findings demonstrate the importance of TNF susceptibility and TNF by-products for recruiting inflammatory cells into the lungs during Ad infections.

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“…E3-14.7K is a hydrophilic nonmembrane protein (30) that may function at or upstream of the proteolytic events that occur early in apoptosis (71). E3-10.4K/14.5K is an integral membrane protein complex (42,43) that is localized in many cellular membranes, including the plasma membrane (32,62,66). E3-14.5K is phosphorylated on serine (45), and it is O glycosylated (44).…”

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confidence: 99%

Adenovirus E3-10.4K/14.5K protein complex inhibits tumor necrosis factor-induced translocation of cytosolic phospholipase A2 to membranes

Dimitrov

Krajcsi

Hermiston

et al. 1997

J Virol

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We have reported that three adenovirus (Ad) proteins, named E3-10.4K/14.5K, E3-14.7K, and E1B-19K, independently inhibit tumor necrosis factor (TNF)-induced apoptosis in Ad-infected cells. E3-10.4K/14.5K and E3-14.7K also inhibit TNF-induced release of arachidonic acid (AA). TNF-induced apoptosis and AA release are thought to require TNF-activation of the 85-kDa cytosolic phospholipase A 2 (cPLA 2). cPLA 2 normally exists in a latent form in the cytosol; it is activated by phosphorylation by mitogen-activated protein kinase, and in the presence of agents that mobilize intracellular Ca 2؉ , cPLA 2 translocates to membranes where it cleaves AA from membrane phospholipids. We now report that TNF induces translocation of cPLA 2 from the cytosol to membranes in Ad-infected human A549 cells and that E3-10.4K/14.5K but not E3-14.7K or E1B-19K is required to inhibit TNF-induced translocation of cPLA 2. Ad infection also inhibited TNF-induced release of AA. Under the same conditions, Ad infection did not inhibit TNF-induced phosphorylation of cPLA 2 or TNF activation of NFB. Ad infection also inhibited cPLA 2 translocation in response to the Ca 2؉ ionophore A23187 and to cycloheximide, but this inhibition did not require E3-10.4K/14.5K. Ad infection did not inhibit cPLA 2 translocation in response to interleukin-1␤ or platelet-derived growth factor. We propose that E3-10.4K/14.5K inhibits TNF-induced AA release and apoptosis by directly or indirectly inhibiting TNF-induced translocation of cPLA 2 from the cytosol to membranes. AA formed by cPLA 2 can be metabolized to prostaglandins, leukotrienes, and lipoxyns, molecules that amplify inflammation. E3-10.4K/14.5K probably functions in Ad infections to inhibit both TNF-induced apoptosis and inflammation.

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The 10,400- and 14,500-dalton proteins encoded by region E3 of adenovirus form a complex and function together to down-regulate the epidermal growth factor receptor

Cited by 85 publications

References 45 publications

Immune evasion by adenoviruses: a window into host–virus adaptation

Immune evasion by adenoviruses: a window into host–virus adaptation

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

Adenovirus E3-10.4K/14.5K protein complex inhibits tumor necrosis factor-induced translocation of cytosolic phospholipase A2 to membranes

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