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| 2. |
- Kullberg-Lindh, Carola, 1959, et al.
(författare)
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Comparison of serum and whole blood levels of cytomegalovirus and Epstein-Barr virus DNA.
- 2008
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Ingår i: Transplant infectious disease : an official journal of the Transplantation Society. - : Wiley. - 1399-3062. ; 10:5, s. 308-15
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Tidskriftsartikel (refereegranskat)abstract
- The monitoring of viral DNA levels after transplantation is crucial for prevention of complications from cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection but there is no consensus as to which matrix is the most adequate. To compare serum and whole blood (WB) as specimens for measuring viral DNA, clinical samples from a 3-year period were studied, with focus on cases where serum and WB were drawn on the same day. In 1896 paired serum and WB samples, CMV DNA was detected in both specimen types in 472 samples with 0.18 log higher levels (P<0.001) in WB than in serum (median level 2.73 vs. 2.56 log copies/mL), and in only either serum or WB in 127 and 108 samples, respectively, generally at levels below 1000 copies/mL. In 664 paired samples, EBV DNA was detected in both serum and WB in 160 samples, with 1.48 log higher levels (P<0.001) in WB (median 4.2 vs. 2.4 log copies/mL), in only WB in 227 cases with a median at 3.0 log copies/mL, and only in serum in 14 samples at low levels. The correlation between serum and WB DNA levels was weaker for EBV than for CMV (R(2) 0.31 vs. 0.74). We conclude that either serum or WB may be used for monitoring CMV and EBV DNA levels, that EBV DNA is detected post transplant in >50% of WB samples and at 30 times higher levels than in serum, and that post-transplantation lymphoproliferative disorder (PTLD) may develop without further increase of EBV DNA in WB. Identification of PTLD may require EBV DNA testing in both specimen types or complementary tests.
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| 3. |
- Kumlin, Urban, et al.
(författare)
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Sialic acid tissue distribution and influenza virus tropism
- 2008
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Ingår i: Influenza and Other Respiratory Viruses. - : Wiley. - 1750-2640 .- 1750-2659. ; 2:5, s. 147-154
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Forskningsöversikt (refereegranskat)abstract
- Avian influenza A viruses exhibit a strong preference for using alpha 2,3-linked sialic acid as a receptor. Until recently, the presumed lack of this receptor in human airways was believed to constitute an efficient barrier to avian influenza A virus infection of humans. Recent zoonotic outbreaks of avian influenza A virus have triggered researchers to analyse tissue distribution of sialic acid in further detail. Here, we review and extend the current knowledge about sialic acid distribution in human tissues, and discuss viruses with ocular tropism and their preference for a2,3-linked sialic acid.
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| 4. |
- Myhre, Susanna, 1974, et al.
(författare)
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Decreased immune reactivity towards a knobless, affibody-targeted adenovirus type 5 vector
- 2007
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Ingår i: Gene Therapy. - : Springer Science and Business Media LLC. - 0969-7128 .- 1476-5462. ; 14:4, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a prototype Adenovirus type 5 (Ad5) vector deleted of the fiber knob domain and carrying an Affibody molecule as the targeting ligand showed decreased susceptibility to human pre-existing antibodies. This vector, Ad5/R7-Z(taq)Z(taq), has short fibers carrying seven shaft repeats, a non-native trimerization signal and an affibody molecule (Z(taq)) reactive to Taq polymerase. Ad5/R7-Z(taq)Z(taq) could be specifically targeted to 293 cells stably expressing membrane-bound anti-Z(taq) idiotypic affibody called Z(ztaq) (293Z(ztaq)). Sera from 50 blood donors were analyzed for neutralization activity (NA) against the parental Ad5/Fiwt vector and knobless Ad5/R7-Z(taq)Z(taq) on 293Z(ztaq) cells. Twenty-three sera had NA titers (>= 1:64) against Ad5/Fiwt (46%) and only two against Ad5/R7-Z(taq)Z(taq) (4%). Characterization of sera with NA titers showed that the knob domain is one of the targets of the antibodies. Neutralization assays using sera pre-adsorbed on knob and hexon proteins showed that the NA of the sera was carried mainly by anti-knob and anti-hexon antibodies, but in certain sera the anti-hexon antibodies represent the major population of the neutralizing antibodies (NAbs). Our results suggested that a combination of knob deletion and hexon switching could be an effective strategy for Ad vectors to better evade the anti-Ad NAbs.
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| 5. |
- Namvar, Lilly, et al.
(författare)
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Detection and typing of Herpes Simplex virus (HSV) in mucocutaneous samples by TaqMan PCR targeting a gB segment homologous for HSV types 1 and 2.
- 2005
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Ingår i: Journal of clinical microbiology. - 0095-1137. ; 43:5, s. 2058-64
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are major causes of mucocutaneous lesions and severe infections of the central nervous system. Here a new semiautomated method for detecting and typing of HSV was used to analyze 479 mucocutaneous swab samples. After DNA extraction using a Magnapure LC robot, a 118-bp segment of the gB region was amplified by real-time PCR utilizing type-specific TaqMan probes to identify HSV-1 or HSV-2. HSV detection in a single well using probes labeled with carboxyfluorescein (FAM) for HSV-1 and JOE (6-carboxy-4',5'-dichloro-2',7'-dimethoxyfluorescein) for HSV-2 had a sensitivity similar to that seen in separate reactions. All but one of 217 samples (99.5%) that had been positive by virus culture were positive by TaqMan PCR, with a correct identification of type in all cases. Out of 262 samples negative by virus culture, 48 (18.3%) were positive by TaqMan PCR, with higher Ct values compared with culture positive samples (P < 0.0001). Overall, the Ct values for HSV-1 were lower than for HSV-2 (mean, 25.5 versus 27.9), but to some extent this could be due to weaker fluorescence by JOE. Lower C(t) values for HSV-1 were seen also in the 202 genital samples (79 HSV-1, 122 HSV-2, 1 HSV-1 and HSV-2), indicating that HSV-1 replicates as well as HSV-2 in the genital area. HSV-1 constituted 40% of genital infections and was associated with lower mean age (29.2 versus 36.4 years), probably reflecting the fact that recurrent genital HSV-1 infections are rare.
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| 6. |
- Norberg, Peter, 1974, et al.
(författare)
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Glycoprotein I of herpes simplex virus type 1 contains a unique polymorphic tandem-repeated mucin region.
- 2007
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 88:Pt 6, s. 1683-8
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Forskningsöversikt (refereegranskat)abstract
- Glycoprotein I (gI) of herpes simplex virus type 1 (HSV-1) contains a tandem repeat (TR) region including the amino acids serine and threonine, residues that can be utilized for O-glycosylation. The length of this TR region was determined for 82 clinical HSV-1 isolates and the results revealed a polymorphic distribution of two to six or eight repeated blocks with a majority harbouring between two and four repeats. Assessment of the O-glycosylation capacity of an acceptor peptide (STPSTTTSTPSTTT), representing two of the gI blocks, showed that the peptide was a universal substrate for O-glycosylation not only for the two most commonly expressed N-acetyl-d-galactosamine (GalNAc)-T1 and -T2 transferases, but also for the GalNAc-T3, -T4 and -T11 transferases. Immunoblotting of virus-infected cells showed that gI was exclusively O-glycosylated with GalNAc monosaccharides (Tn antigen). A polymorphic mucin region has not been described previously for HSV-1 and is a unique finding, as repeated blocks within gI homologues are lacking in other alphaherpesviruses.
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| 7. |
- Nordén, Rickard, 1977, et al.
(författare)
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Activation of host antiviral RNA-sensing factors necessary for herpes simplex virus type 1-activated transcription of host cell fucosyltransferase genes FUT3, FUT5, and FUT6 and subsequent expression of sLex in virus-infected cells.
- 2009
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 19:7, s. 776-88
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus type 1 (HSV-1) induces expression of a selectin receptor, the carbohydrate epitope sialyl Lewis X (sLe(x)), at the surface of infected cells. The molecular background to this phenomenon is that a viral immediate early RNA interacts with as yet unidentified host factors, eventually resulting in transcription of three dormant host fucosyltransferase genes (FUT3, FUT5, and FUT6), whose gene products are rate-limiting for synthesis of sLe(x). The aim of the present study was to define the immediate targets for the viral RNA in this process. We found that the Protein Kinase R (PKR) inhibitors 2-aminopurine (2-AP) and C16 inhibited FUT3, FUT5, and FUT6 expression as well as HSV-1-induced expression of sLe(x), indicating a primary role of PKR as a viral RNA target. The PKR-dependent activation of the FUT genes seemed neither to involve PKR effects on translation nor to involve NF-kappaB- or JNK-dependent activation. IMD-0354, known as an inhibitor of the NF-kappaB-activating factor IKK-2, induced FUT transcription via a novel IKK-2-independent mechanism, irrespective of whether the cells were virus-infected or not. Altogether, the results suggested that PKR is the primary target for HSV-1 early RNA during induction of FUT3, FUT5, and FUT6, and that the subsequent steps in the transcriptional activation of these host genes involve a hitherto unknown IMD-0354, yet IKK-2-independent, pathway.
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| 8. |
- Nyström, Kristina, 1977, et al.
(författare)
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Induction of sialyl-Lex expression by herpes simplex virus type 1 is dependent on viral immediate early RNA-activated transcription of host fucosyltransferase genes. : Induction of sialyl-Lewis x expression by HSV-1
- 2009
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 19:8, s. 847-59
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that varicella-zoster virus (VZV) and cytomegalovirus (CMV) infection of diploid human fibroblasts (HEL) results in neo-expression of Lewis antigens sialyl Lewis x (sLe(x)) and Lewis y (Le(y)), respectively, after transcriptional activation of different combinations of dormant human fucosyltransferase genes (FUT1, FUT3, FUT5, and FUT6), whose gene products are responsible for the synthesis of Le antigens. Here, we show that herpes simplex virus type 1 (HSV-1) also induces sLe(x) expression dependent on induction of FUT3, FUT5, and FUT6 transcription in infected cells. HSV-1 induction of FUT5 was subsequently used as a model system for analyzing the mechanism of viral activation of dormant fucosyltransferase genes. We show that this is a rapid process, which gives rise to elevated FUT5 RNA levels already at 90 min postinfection. Augmented FUT5 transcription was found to be dependent on transcription of viral genes, but not dependent on the immediate early proteins ICP0 and ICP4, as demonstrated by experiments with HSV-1 mutants defective in expression of these genes. Augmented FUT5 transcription takes place in cycloheximide-treated HSV-1-infected cells, suggesting a more direct role for IE viral RNA during activation of cellular FUT5.
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| 9. |
- Nyström, Kristina, 1977, et al.
(författare)
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Virus-induced transcriptional activation of host FUT genes associated with neo-expression of Ley in cytomegalovirus-infected and sialyl-Lex in varicella-zoster virus-infected diploid human cells
- 2007
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 17:4, s. 355-66
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Tidskriftsartikel (refereegranskat)abstract
- Cell surface carbohydrate structures including sialyl-Lewis X (sLe(x)) and Lewis Y (Le(y)) are important ligands in normal and malignant tissues. The aim here was to determine the possible influence on the expression of such antigens by two viruses varicella-zoster virus (VZV) and cytomegalovirus (CMV) involved in persistent infections of humans. We found that infection of human diploid fibroblasts with both viruses resulted in transcriptional activation of several fucosyltransferase (FUT) genes that were either dormant or expressed at low levels in uninfected cells. Both viruses induced FUT3, FUT5, and FUT6, encoding alpha1,3- and/or alpha1,4-specific fucosyltransferases. CMV, but not VZV, induced transcription of FUT1 (encoding an alpha1,2-specific fucosyltransferase), FUT7, and FUT9. The changes in transcription of FUT genes were expectedly associated with expression of Le(y) in CMV-infected cells and sLe(x) in the VZV-infected fibroblasts although no expression of these antigens was observed in uninfected cells. One major explanation for this difference between CMV- and VZV-infected cells was that CMV, but not VZV, induced expression of FUT1, necessary for Le(y) expression. The induced carbohydrate antigens in CMV- and VZV-infected cells could be of significance for virus spread and possible escape from immune responses.
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