FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2317667706> ?p ?o ?g. }

• W2317667706 endingPage "3943" @default.
• W2317667706 startingPage "3929" @default.
• W2317667706 abstract "Clinical human cytomegalovirus (HCMV) strains invariably mutate when propagatedin vitro Mutations in gene RL13 are selected in all cell types, whereas in fibroblasts mutants in the UL128 locus (UL128L; genes UL128, UL130, and UL131A) are also selected. In addition, sporadic mutations are selected elsewhere in the genome in all cell types. We sought to investigate conditions under which HCMV can be propagated without incurring genetic defects. Bacterial artificial chromosomes (BACs) provide a stable, genetically defined source of viral genome. Viruses were generated from BACs containing the genomes of strains TR, TB40, FIX, and Merlin, as well as from Merlin-BAC recombinants containing variant nucleotides in UL128L from TB40-BAC4 or FIX-BAC. Propagation of viruses derived from TR-BAC, TB40-BAC4, and FIX-BAC in either fibroblast or epithelial cells was associated with the generation of defects around the prokaryotic vector, which is retained in the unique short (US) region of viruses. This was not observed for Merlin-BAC, from which the vector is excised in derived viruses; however, propagation in epithelial cells was consistently associated with mutations in the unique longb' (UL/b') region, all impacting on gene UL141. Viruses derived from Merlin-BAC in fibroblasts had mutations in UL128L, but mutations occurred less frequently with recombinants containing UL128L nucleotides from TB40-BAC4 or FIX-BAC. Viruses derived from a Merlin-BAC derivative in which RL13 and UL128L were either mutated or repressed were remarkably stable in fibroblasts. Thus, HCMV containing a wild-type gene complement can be generatedin vitroby deriving virus from a self-excising BAC in fibroblasts and repressing RL13 and UL128L.Researchers should aim to study viruses that accurately represent the causative agents of disease. This is problematic for HCMV because clinical strains mutate rapidly when propagatedin vitro, becoming less cell associated, altered in tropism, more susceptible to natural killer cells, and less pathogenic. Following isolation from clinical material, HCMV genomes can be stabilized by cloning into bacterial artificial chromosomes (BACs), and then virus is regenerated by DNA transfection. However, mutations can occur not only during isolation prior to BAC cloning but also when virus is regenerated. We have identified conditions under which BAC-derived viruses containing an intact, wild-type genome can be propagatedin vitrowith minimal risk of mutants being selected, enabling studies of viruses expressing the gene complement of a clinical strain. However, even under these optimized conditions, sporadic mutations can occur, highlighting the advisability of sequencing the HCMV stocks used in experiments." @default.
• W2317667706 created "2016-06-24" @default.
• W2317667706 creator A5016233857 @default.
• W2317667706 creator A5018240758 @default.
• W2317667706 creator A5019497100 @default.
• W2317667706 creator A5031063826 @default.
• W2317667706 creator A5039230558 @default.
• W2317667706 creator A5059195011 @default.
• W2317667706 creator A5061315953 @default.
• W2317667706 creator A5063522604 @default.
• W2317667706 date "2016-04-15" @default.
• W2317667706 modified "2023-10-11" @default.
• W2317667706 title "Genetic Stability of Bacterial Artificial Chromosome-Derived Human Cytomegalovirus during Culture <i>In Vitro</i>" @default.
• W2317667706 cites W1521875557 @default.
• W2317667706 cites W1545455594 @default.
• W2317667706 cites W1564118140 @default.
• W2317667706 cites W1576230074 @default.
• W2317667706 cites W1608297032 @default.
• W2317667706 cites W1769850054 @default.
• W2317667706 cites W1963943606 @default.
• W2317667706 cites W1965971941 @default.
• W2317667706 cites W1971414812 @default.
• W2317667706 cites W1971617325 @default.
• W2317667706 cites W1973708619 @default.
• W2317667706 cites W1981892114 @default.
• W2317667706 cites W1996749102 @default.
• W2317667706 cites W1996760659 @default.
• W2317667706 cites W2005520265 @default.
• W2317667706 cites W2005693124 @default.
• W2317667706 cites W2014499991 @default.
• W2317667706 cites W2014516979 @default.
• W2317667706 cites W2015193281 @default.
• W2317667706 cites W2019284105 @default.
• W2317667706 cites W2027486540 @default.
• W2317667706 cites W2029345949 @default.
• W2317667706 cites W2032715845 @default.
• W2317667706 cites W2033168971 @default.
• W2317667706 cites W2042418697 @default.
• W2317667706 cites W2045944192 @default.
• W2317667706 cites W2050424221 @default.
• W2317667706 cites W2051167712 @default.
• W2317667706 cites W2052387773 @default.
• W2317667706 cites W2054515639 @default.
• W2317667706 cites W2056309685 @default.
• W2317667706 cites W2064890413 @default.
• W2317667706 cites W2066964567 @default.
• W2317667706 cites W2075038248 @default.
• W2317667706 cites W2075517421 @default.
• W2317667706 cites W2077397079 @default.
• W2317667706 cites W2080594248 @default.
• W2317667706 cites W2087077422 @default.
• W2317667706 cites W2088724200 @default.
• W2317667706 cites W2093619247 @default.
• W2317667706 cites W2095651237 @default.
• W2317667706 cites W2096963698 @default.
• W2317667706 cites W2100595637 @default.
• W2317667706 cites W2103441770 @default.
• W2317667706 cites W2104219682 @default.
• W2317667706 cites W2106045063 @default.
• W2317667706 cites W2109528932 @default.
• W2317667706 cites W2111485125 @default.
• W2317667706 cites W2112256325 @default.
• W2317667706 cites W2114858538 @default.
• W2317667706 cites W2117208489 @default.
• W2317667706 cites W2118937969 @default.
• W2317667706 cites W2119751382 @default.
• W2317667706 cites W2121446424 @default.
• W2317667706 cites W2121749962 @default.
• W2317667706 cites W2122270655 @default.
• W2317667706 cites W2124076428 @default.
• W2317667706 cites W2127258151 @default.
• W2317667706 cites W2128159409 @default.
• W2317667706 cites W2132275721 @default.
• W2317667706 cites W2134270419 @default.
• W2317667706 cites W2135134003 @default.
• W2317667706 cites W2135751988 @default.
• W2317667706 cites W2136129244 @default.
• W2317667706 cites W2139567694 @default.
• W2317667706 cites W2140404757 @default.
• W2317667706 cites W2140839431 @default.
• W2317667706 cites W2141401084 @default.
• W2317667706 cites W2141755034 @default.
• W2317667706 cites W2151561269 @default.
• W2317667706 cites W2157832000 @default.
• W2317667706 cites W2159292028 @default.
• W2317667706 cites W2159518657 @default.
• W2317667706 cites W2159916488 @default.
• W2317667706 cites W2161539371 @default.
• W2317667706 cites W2161607487 @default.
• W2317667706 cites W2165587647 @default.
• W2317667706 cites W2168491172 @default.
• W2317667706 cites W2169067144 @default.
• W2317667706 cites W2170651190 @default.
• W2317667706 cites W48780628 @default.
• W2317667706 doi "https://doi.org/10.1128/jvi.02858-15" @default.
• W2317667706 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4810542" @default.
• W2317667706 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26842472" @default.
• W2317667706 hasPublicationYear "2016" @default.

• next