FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2774239504> ?p ?o ?g. }

• W2774239504 abstract "Human cytomegalovirus (HCMV) is the top viral cause of birth defects worldwide, and current therapies have high toxicity. We previously reported that the mTOR-independent autophagy-inducing disaccharide trehalose inhibits HCMV replication in multiple cell types. Here, we examine the mechanism of inhibition and introduce the autophagy inducer SMER28 as an additional inhibitor of HCMV acting through a different mechanism. We find that trehalose induces vacuolation and acidification of vacuoles and that debris, including debris with an appearance consistent with that of abnormal virions, is present in multivesicular bodies. Trehalose treatment increased the levels of Rab7, a protein required for lysosomal biogenesis and fusion, and slightly decreased the levels of Rab11, which is associated with recycling endosomes. We also present evidence that trehalose can promote autophagy without altering cellular glucose uptake. We show that SMER28 inhibits HCMV at the level of early protein production and interferes with viral genome replication in a cell type-dependent fashion. Finally, we show that SMER28 treatment does not cause the vacuolation, acidification, or redistribution of Rab7 associated with trehalose treatment and shows only a modest and cell type-dependent effect on autophagy. We propose a model in which the reciprocal effects on Rab7 and Rab11 induced by trehalose contribute to the redirection of enveloped virions from the plasma membrane to acidified compartments and subsequent degradation, and SMER28 treatment results in decreased expression levels of early and late proteins, reducing the number of virions produced without the widespread vacuolation characteristic of trehalose treatment.IMPORTANCE There is a need for less toxic HCMV antiviral drugs, and modulation of autophagy to control viral infection is a new strategy that takes advantage of virus dependence on autophagy inhibition. The present study extends our previous work on trehalose by showing a possible mechanism of action and introduces another autophagy-inducing compound, SMER28, that is effective against HCMV in several cell types. The mechanism by which trehalose induces autophagy is currently unknown, although our data show that trehalose does not inhibit cellular glucose uptake in cells relevant for HCMV replication but instead alters virion degradation by promoting acidic vacuolization. The comparison of our cell types and those used by others highlights the cell type-dependent nature of studying autophagy." @default.
• W2774239504 created "2017-12-22" @default.
• W2774239504 creator A5038608536 @default.
• W2774239504 creator A5044473904 @default.
• W2774239504 creator A5052328406 @default.
• W2774239504 creator A5071705587 @default.
• W2774239504 date "2018-03-15" @default.
• W2774239504 modified "2023-10-14" @default.
• W2774239504 title "Human Cytomegalovirus Replication Is Inhibited by the Autophagy-Inducing Compounds Trehalose and SMER28 through Distinctively Different Mechanisms" @default.
• W2774239504 cites W1523639188 @default.
• W2774239504 cites W1542338679 @default.
• W2774239504 cites W1884484468 @default.
• W2774239504 cites W1901313370 @default.
• W2774239504 cites W1975248583 @default.
• W2774239504 cites W1979661536 @default.
• W2774239504 cites W1979921905 @default.
• W2774239504 cites W1988044873 @default.
• W2774239504 cites W1990437594 @default.
• W2774239504 cites W1994668150 @default.
• W2774239504 cites W1998916177 @default.
• W2774239504 cites W2015614892 @default.
• W2774239504 cites W2021304970 @default.
• W2774239504 cites W2021335029 @default.
• W2774239504 cites W2026239217 @default.
• W2774239504 cites W2028050122 @default.
• W2774239504 cites W2032067173 @default.
• W2774239504 cites W2039725815 @default.
• W2774239504 cites W2042885383 @default.
• W2774239504 cites W2048444754 @default.
• W2774239504 cites W2049142865 @default.
• W2774239504 cites W2054448479 @default.
• W2774239504 cites W2058379910 @default.
• W2774239504 cites W2061757869 @default.
• W2774239504 cites W2064949318 @default.
• W2774239504 cites W2070651559 @default.
• W2774239504 cites W2087098731 @default.
• W2774239504 cites W2104399354 @default.
• W2774239504 cites W2105630799 @default.
• W2774239504 cites W2107621349 @default.
• W2774239504 cites W2110645858 @default.
• W2774239504 cites W2111433992 @default.
• W2774239504 cites W2115394517 @default.
• W2774239504 cites W2116012460 @default.
• W2774239504 cites W2152148024 @default.
• W2774239504 cites W2154249083 @default.
• W2774239504 cites W2161932769 @default.
• W2774239504 cites W2164778558 @default.
• W2774239504 cites W2165480619 @default.
• W2774239504 cites W2178245835 @default.
• W2774239504 cites W2195174090 @default.
• W2774239504 cites W2197424077 @default.
• W2774239504 cites W2199487085 @default.
• W2774239504 cites W2221448846 @default.
• W2774239504 cites W2274106113 @default.
• W2774239504 cites W2286285703 @default.
• W2774239504 cites W2295011570 @default.
• W2774239504 cites W2321937006 @default.
• W2774239504 cites W2337821328 @default.
• W2774239504 cites W2398892968 @default.
• W2774239504 cites W2411196497 @default.
• W2774239504 cites W2462657557 @default.
• W2774239504 cites W2507116321 @default.
• W2774239504 cites W2510702289 @default.
• W2774239504 cites W2511932783 @default.
• W2774239504 cites W2534368867 @default.
• W2774239504 cites W2560346274 @default.
• W2774239504 cites W2586932047 @default.
• W2774239504 cites W2587718283 @default.
• W2774239504 cites W2591512602 @default.
• W2774239504 cites W2609372546 @default.
• W2774239504 cites W2777734899 @default.
• W2774239504 doi "https://doi.org/10.1128/jvi.02015-17" @default.
• W2774239504 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5827393" @default.
• W2774239504 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29237845" @default.
• W2774239504 hasPublicationYear "2018" @default.
• W2774239504 type Work @default.
• W2774239504 sameAs 2774239504 @default.
• W2774239504 citedByCount "17" @default.
• W2774239504 countsByYear W27742395042020 @default.
• W2774239504 countsByYear W27742395042021 @default.
• W2774239504 countsByYear W27742395042022 @default.
• W2774239504 countsByYear W27742395042023 @default.
• W2774239504 crossrefType "journal-article" @default.
• W2774239504 hasAuthorship W2774239504A5038608536 @default.
• W2774239504 hasAuthorship W2774239504A5044473904 @default.
• W2774239504 hasAuthorship W2774239504A5052328406 @default.
• W2774239504 hasAuthorship W2774239504A5071705587 @default.
• W2774239504 hasBestOaLocation W27742395041 @default.
• W2774239504 hasConcept C102568950 @default.
• W2774239504 hasConcept C102747710 @default.
• W2774239504 hasConcept C140704245 @default.
• W2774239504 hasConcept C159047783 @default.
• W2774239504 hasConcept C190062978 @default.
• W2774239504 hasConcept C190283241 @default.
• W2774239504 hasConcept C203522944 @default.
• W2774239504 hasConcept C2522874641 @default.
• W2774239504 hasConcept C2778452849 @default.
• W2774239504 hasConcept C2779820661 @default.
• W2774239504 hasConcept C55493867 @default.
• W2774239504 hasConcept C79879829 @default.

• next