Adenovirus E1A proteins stimulate inositol phospholipid metabolism in PC12 cells

Shiroki, Kazuko; Yamakawa, Akira; Shibata, Michihiro; Takenawa, Tadaomi; Sugano, Shigeru; Nomoto, Akio

doi:10.1128/jvi.66.10.6093-6098.1992

Cited by 6 publications

(1 citation statement)

References 42 publications

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“…However, caution should be taken when interpreting each of these results. The HEK293T, and HEK293T derived HEK293FT cells, used for KO of IPPK or IPMK in references 17 and 27 express viral oncogenes that manipulate steady state inositol phosphates levels [38,39]. Second, ectopic expression of MINPP1 in IPPK KO HEK293FT cells was cytotoxic, making it difficult to interpret the results using this method [27].…”

Section: Plos Pathogensmentioning

confidence: 99%

Inositol phosphates promote HIV-1 assembly and maturation to facilitate viral spread in human CD4+ T cells

Sowd

Aiken

2021

PLoS Pathog

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Gag polymerization with viral RNA at the plasma membrane initiates HIV-1 assembly. Assembly processes are inefficient in vitro but are stimulated by inositol (1,3,4,5,6) pentakisphosphate (IP5) and inositol hexakisphosphate (IP6) metabolites. Previous studies have shown that depletion of these inositol phosphate species from HEK293T cells reduced HIV-1 particle production but did not alter the infectivity of the resulting progeny virions. Moreover, HIV-1 substitutions bearing Gag/CA mutations ablating IP6 binding are noninfectious with destabilized viral cores. In this study, we analyzed the effects of cellular depletion of IP5 and IP6 on HIV-1 replication in T cells in which we disrupted the genes encoding the kinases required for IP6 generation, IP5 2-kinase (IPPK) and Inositol Polyphosphate Multikinase (IPMK). Knockout (KO) of IPPK from CEM and MT-4 cells depleted cellular IP6 in both T cell lines, and IPMK disruption reduced the levels of both IP5 and IP6. In the KO lines, HIV-1 spread was delayed relative to parental wild-type (WT) cells and was rescued by complementation. Virus release was decreased in all IPPK or IPMK KO lines relative to WT cells. Infected IPMK KO cells exhibited elevated levels of intracellular Gag protein, indicative of impaired particle assembly. IPMK KO compromised virus production to a greater extent than IPPK KO suggesting that IP5 promotes HIV-1 particle assembly in IPPK KO cells. HIV-1 particles released from infected IPPK or IPMK KO cells were less infectious than those from WT cells. These viruses exhibited partially cleaved Gag proteins, decreased virion-associated p24, and higher frequencies of aberrant particles, indicative of a maturation defect. Our data demonstrate that IP6 enhances the quantity and quality of virions produced from T cells, thereby preventing defects in HIV-1 replication.

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Section: Plos Pathogensmentioning

confidence: 99%

Inositol phosphates promote HIV-1 assembly and maturation to facilitate viral spread in human CD4+ T cells

Sowd

Aiken

2021

PLoS Pathog

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Adenovirus and protein kinase C have distinct molecular requirements for regulating epidermal growth factor receptor trafficking

Hoffman

Takishima

Rosner

et al. 1993

Journal Cellular Physiology

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The ligand-activated tyrosine kinase receptor for epidermal growth factor (EGF) is down-regulated by an integral membrane protein coded for by the E3 early transcription unit of group C adenoviruses. The E3 protein appears to block recycling of constitutively internalized receptors, causing them instead to traffic to lysosomes where they are degraded. Expression of functional EGF receptors is also regulated by protein kinase C (PKC), which directly phosphorylates the EGF receptor at Thr-654. The goal of this study was to determine potential interactions between PKC and the E3 protein, since membrane-bound PKC activity is elevated by the adenovirus E1A protein. Our results show that although tumor promoters which activate PKC cause a coordinate induction of E3 protein synthesis and EGF receptor degradation, the E3 protein-induced pathway for receptor down-regulation functions independently of PKC and other kinases that are inhibited by staurosporine. This suggests that in contrast to other mechanisms that modulate receptor expression (i.e., ligand and PKC), the E3 protein is not regulated by phosphorylation but is constitutively active. We also report that adenovirus-mediated degradation is the preferred pathway in infected cells stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) to induce receptor recycling.

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Programmed cell death of PC12 induced by adenovirus E1A

Sawada

Kondo

Marunouchi

1995

Neuroscience Letters

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Adenovirus E1A proteins stimulate inositol phospholipid metabolism in PC12 cells

Cited by 6 publications

References 42 publications

Inositol phosphates promote HIV-1 assembly and maturation to facilitate viral spread in human CD4+ T cells

Inositol phosphates promote HIV-1 assembly and maturation to facilitate viral spread in human CD4+ T cells

Adenovirus and protein kinase C have distinct molecular requirements for regulating epidermal growth factor receptor trafficking

Programmed cell death of PC12 induced by adenovirus E1A

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