| 1. |
- Forslund, Ola, et al.
(författare)
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Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish Women.
- 2002
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Ingår i: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 66:4, s. 535-541
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32-38 years were analyzed using a general HPV primer (GP5(+)/6(+)) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2-7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy.
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| 2. |
- Skog, Johan, et al.
(författare)
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Efficient internalization into low-passage glioma cell lines using adenoviruses other than type 5: an approach for improvement of gene delivery to brain tumours
- 2004
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 84:9, s. 2627-2638
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for improvement of the commonly used adenovirus vectors based on serotype 5. This study was performed on three adenovirus serotypes with a CAR-binding motif (Ad4p, Ad5p and Ad17p) and three non-CAR-binding serotypes (Ad11p, Ad16p and Ad21p). The capacity of these alternative adenovirus vector candidates to deliver DNA into low-passage glioma cell lines from seven different donors was evaluated. The non-CAR-binding serotype Ad16p was the most efficient serotype with regard to import of its DNA, as well as initiation of hexon protein expression. Ad16p established hexon expression in 60–80 % of the cell population in gliomas from all donors tested. The other non-CAR-binding serotypes, Ad11p and Ad21p, showed hexon expression in 25–60 and 40–80 % of cells, respectively. The corresponding figure for the best CAR-binding serotype, Ad5p, was only 25–65 %, indicating greater variability between cells from different donors than serotype Ad16p had. The other CAR-binding serotypes, Ad4p and Ad17p, were refractory to some of the gliomas, giving a maximum of only 45 and 40 % hexon expression, respectively, in the most permissive cells. Interestingly, the transduction capacity of the CAR-binding serotypes was not correlated to the level of CAR expression on the cells.
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| 3. |
- Arnberg, Niklas, et al.
(författare)
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Adenovirus type 37 binds to cell surface sialic acid through a charge-dependent interaction
- 2002
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Ingår i: Virology. - : Elsevier. - 0042-6822 .- 1096-0341. ; 302:1, s. 33-43
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Tidskriftsartikel (refereegranskat)abstract
- Most adenoviruses use the coxsackie-adenovirus receptor (CAR) as a major cellular receptor. We have shown recently that adenovirus types 8, 19a, and 37, which are the major causes of epidemic keratoconjunctivitis, use sialic acid rather than CAR as a major cellular receptor. The predicted isoelectric point of the receptor-interacting knob domain in the adenovirus fiber protein is unusually high (9.0-9.1) in type 8, 19a, and 37. The pKa of sialic acid is low, 2.6, implying a possible involvement of charge in fiber knob-sialic acid interactions. Here we show that (i) positively charged adenovirus knobs require sialic acid for efficient cell membrane interactions; (ii) viral and knob interactions with immobilized sialic acid or cell-surface sialic acid are sensitive to increased ionic strength; (iii) negatively charged molecules such as sulfated glycosaminoglycans inhibit the binding of virions to target cells in a nonspecific, charge-dependent manner; and that (iv) the ability of adenovirus knobs to interact with sialic acid correlates with the overall charge on the top surface of the respective knobs as predicted by homology modeling. Taken together, the results presented provide strong evidence for a charge mechanism during the interaction between the Ad37 fiber knob and sialic acid.
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| 4. |
- Arnberg, Niklas, et al.
(författare)
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Adenovirus type 37 uses sialic acid as a cellular receptor
- 2000
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Ingår i: Journal of Virology. - 0022-538X .- 1098-5514. ; 74:1, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- Two cellular receptors for adenovirus, coxsackievirus-adenovirus receptor (CAR) and major histocompatibility complex class I (MHC-I) alpha2, have recently been identified. In the absence of CAR, MHC-I alpha2 has been suggested to serve as a cellular attachment protein for subgenus C adenoviruses, while members from all subgenera except subgenus B have been shown to interact with CAR. We have found that adenovirus type 37 (Ad37) attachment to CAR-expressing CHO cells was no better than that to CHO cells lacking CAR expression, suggesting that CAR is not used by Ad37 during attachment. Instead, we have identified sialic acid as a third adenovirus receptor moiety. First, Ad37 attachment to both CAR-expressing CHO cells and MHC-I alpha2-expressing Daudi cells was sensitive to neuraminidase treatment, which eliminates sialic acid on the cell surface. Second, Ad37 attachment to sialic acid-expressing Pro-5 cells was more than 10-fold stronger than that to the Pro-5 subline Lec2, which is deficient in sialic acid expression. Third, neuraminidase treatment of A549 cells caused a 60% decrease in Ad37 replication in a fluorescent-focus assay. Moreover, the receptor sialoconjugate is most probably a glycoprotein rather than a ganglioside, since Ad37 attachment to sialic acid-expressing Pro-5 cells was sensitive to protease treatment. Ad37 attachment to Pro-5 cells occurs via alpha(2-->3)-linked sialic acid saccharides rather than alpha(2-->6)-linked ones, since (i) alpha(2-->3)-specific but not alpha(2-->6)-specific lectins blocked Ad37 attachment to Pro-5 cells and (ii) pretreatment of Pro-5 cells with alpha(2-->3)-specific neuraminidase resulted in decreased Ad37 binding. Taken together, these results suggest that, unlike Ad5, Ad37 makes use of alpha(2-->3)-linked sialic acid saccharides on glycoproteins for entry instead of using CAR or MHC-I alpha2.
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| 5. |
- Arnberg, Niklas, et al.
(författare)
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Adenovirus type 37 uses sialic acid as a cellular receptor on Chang C cells
- 2002
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 76:17, s. 8834-8841
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Tidskriftsartikel (refereegranskat)abstract
- Epidemic keratoconjunctivitis (EKC) is a severe eye infection caused mainly by adenovirus type 8 (Ad8), Ad19, and Ad37. We have shown that the EKC-causing adenoviruses use sialic acid as a cellular receptor on A549 cells instead of the coxsackie-adenovirus receptor, which is used by most adenoviruses. Recently, Wu et al. (Virology 279:78-89, 2001) proposed that Ad37 uses a 50-kDa protein as a receptor on Chang C conjunctival cells and that this interaction is independent of sialic acid. According to the American Type Culture Collection, this cell line carries HeLa cell markers and should be considered to be a genital cell line. This prompted us to investigate the function of sialic acid as a cellular receptor for Ad37 in Chang C cells. In this study, we demonstrate that enzymatic removal or lectin-mediated blocking of cell surface sialic acid inhibits the binding of Ad37 virions to Chang C cells, as does soluble, virion-interacting sialic acid-containing substances. The binding was Ca2+ or Mg2+ ion independent and mediated by the knob domain of the trimeric viral fiber polypeptide. Moreover, Ad37 virions infected Chang C cells and two other genital cell lines (HeLa and SiHa) as well as a corneal cell line in a strictly sialic acid-dependent manner. From these results, we conclude that Ad37 uses sialic acid as a major receptor in cell lines derived from both genital and corneal tissues.
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| 6. |
- Arnberg, Niklas, et al.
(författare)
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Initial interactions of subgenus D adenoviruses with A549 cellular receptors : sialic acid versus alpha(v) integrins
- 2000
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Ingår i: Journal of Virology. - 0022-538X .- 1098-5514. ; 74:16, s. 7691-3
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Tidskriftsartikel (refereegranskat)abstract
- Selected members of the adenovirus family have been shown to interact with the coxsackie adenovirus receptor, alpha(v) integrins, and sialic acid on target cells. Initial interactions of subgenus D adenoviruses with target cells have until now been poorly characterized. Here, we demonstrate that adenovirus type 8 (Ad8), Ad19a, and Ad37 use sialic acid as a functional cellular receptor, whereas the Ad9 and Ad19 prototypes do not.
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| 7. |
- Burmeister, Wim P, et al.
(författare)
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Crystal structure of species D adenovirus fiber knobs and their sialic acid binding sites
- 2004
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 78:14, s. 7727-7736
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Tidskriftsartikel (refereegranskat)abstract
- Adenovirus serotype 37 (Ad37) belongs to species D and can cause epidemic keratoconjunctivitis, whereas the closely related Ad19p does not. Primary cell attachment by adenoviruses is mediated through receptor binding of the knob domain of the fiber protein. The knobs of Ad37 and Ad19p differ at only two positions, Lys240Glu and Asn340Asp. We report the high-resolution crystal structures of the Ad37 and Ad19p knobs, both native and in complex with sialic acid, which has been proposed as a receptor for Ad37. Overall, the Ad37 and Ad19p knobs are very similar to previously reported knob structures, especially to that of Ad5, which binds the coxsackievirus-adenovirus receptor (CAR). Ad37 and Ad19p knobs are structurally identical with the exception of the changed side chains and are structurally most similar to CAR-binding knobs (e.g., that of Ad5) rather than non-CAR-binding knobs (e.g., that of Ad3). The two mutations in Ad19p result in a partial loss of the exceptionally high positive surface charge of the Ad37 knob but do not affect sialic acid binding. This site is located on the top of the trimer and binds both alpha(2,3) and alpha(2,6)-linked sialyl-lactose, although only the sialic acid residue makes direct contact. Amino acid alignment suggests that the sialic acid binding site is conserved in several species D serotypes. Our results show that the altered viral tropism and cell binding of Ad19p relative to those of Ad37 are not explained by a different binding ability toward sialyl-lactose.
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| 8. |
- Mei, Ya-Fang, et al.
(författare)
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Comparative analysis of the genome organization of human adenovirus 11, a member of the human adenovirus species B, and the commonly used human adenovirus 5 vector, a member of species C
- 2003
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 84:8, s. 2061-2071
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Tidskriftsartikel (refereegranskat)abstract
- Adenovirus type 11 (Ad11), a member of the human adenovirus species B (HAdV-B), has a tropism for the urinary tract. The genome of Ad11 was found to comprise 34 794 bp and is 1141 bp shorter than the Ad5 genome of species HAdV-C. The G+C content of the Ad11 genome is 48.9 %, whereas that of Ad5 is 55.2 %. Ad11 and Ad5 share 57 % nucleotide identity and possess the same four early regions, but the E3 region of Ad11 could not be divided into E3A and E3B. The late genes of Ad11 and Ad5 are organized into six and five regions, respectively. Thirty-eight putative ORFs were identified in the Ad11 genome. The ORFs in the late regions, the E2B region and IVa2 show high amino acid identity between Ad11 and Ad5, whereas the ORFs in E1, E2A, E3 and E4, protein IX and the fibre protein show low amino acid identity. The highest and lowest identities were noted in the pre-terminal protein and fibre proteins: 85 % and 24.6 %, respectively. The E3 20.3K and 20.6K ORFs and the L6 agnoprotein were present in the Ad11 genome only, whereas the E3 11.6K cell death protein was identified only in Ad5. All ORFs but the E3 10.3K and L4 pVIII protein vary not only in composition but also in size. Ad11 may have a higher vector capacity than Ad5, since it has a shorter genome and a shorter fibre. Furthermore, in the E3 region, two additional ORFs can be deleted to give extra capacity for foreign DNA.
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| 9. |
- Mei, Ya-Fang, et al.
(författare)
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Human adenoviruses of subgenera B, C, and E with various tropisms differ in both binding to and replication in the epithelial A549 and 293 cells
- 2002
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Ingår i: Virology. - : Elsevier. - 0042-6822 .- 1096-0341. ; 295:1, s. 30-43
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Tidskriftsartikel (refereegranskat)abstract
- Adenoviruses of six subgenera, namely, adenovirus 31 (Ad31) (subgenus A), Ad3, Ad7, Ad11p, Ad11a, and Ad35 (subgenus B), Ad5v and Ad5p (subgenus C), Ad37 (subgenus D), Ad4 (subgenus E), and Ad41 (subgenus F), were studied. The relative binding properties of different adenoviruses to 293 (human kidney embryonic cells) and A549 (human lung carcinoma cells) cells were compared by flow cytometry. All analyzed adenoviruses bound to cells in a dose-dependent manner. The binding capacity showed that Ad11p, Ad35 (subgenus B:2) with kidney tropism, and Ad4 (subgenus E), which can cause adenopharyngoconjunctivitis, bound strongly to both A549 and 293 cells. The other members of subgenus B and Ad37 of subgenus D manifested an intermediate binding capacity. The analyzed adenoviruses of subgenera A, C, and F manifested a low affinity. Adenoviruses of subgenera B:2 and E manifested high binding affinity to preparations of cell membranes from the epithelial cell lines. Reciprocal competition experiments using Ad11p and Ad4 demonstrated that the two viruses did not block each other. Antibodies against alphavbeta3 and alphavbeta5 reduced the binding of Ad5v virions and slightly impaired the binding of Ad4 but did not affect Ad11p binding to the A549 cell surface. Recombinant fiber proteins of Ad11p and Ad35 reciprocally blocked the binding of both viruses to the epithelial cells but they could not block Ad4. The hexon protein expression of Ad11p and Ad4 was 100 times more efficient than that of the Ad5 vector (pFG140), whereas the infectivity of Ad11p and Ad4 was 40- to 200-fold that of the commonly used Ad5v vector. Taken together, our findings demonstrate that Ad11p and Ad4 bind different receptor molecules and that the fibers of these two viruses provide the predominant high degree of binding, which obviously is a requirement for subsequent internalization and efficacious expression.
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| 10. |
- Mei, Ya-Fang, et al.
(författare)
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Human hematopoietic (CD34+) stem cells possess high-affinity receptors for adenovirus type 11p
- 2004
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Ingår i: Virology. - : Elsevier BV. - 0042-6822 .- 1096-0341. ; 328:2, s. 198-207
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Tidskriftsartikel (refereegranskat)abstract
- Gene transfer into human hematopoietic stem cells using Ad5 is inefficient due to lack of the primary receptor CAR and the secondary receptors alphavbeta3 integrin and alphavbeta5 integrin, and due to the high seroprevalence of Ad5 antibodies in most adults, resulting in diminished gene transduction. In the present study, we screened six species (species A-F) of adenovirus, displaying different tropisms for interaction with CD34+ cells, at the level of virus attachment and expression. Virus particles were biotinylated and their binding capacity was determined by FACS analysis using streptavidin-FITC. Ad11p, Ad35, and Ad3 (species B) showed high binding affinity, while Ad7, Ad11a (species B), and Ad37 (species D) displayed intermediate affinity. Virions of Ad4 (species E), Ad5 (species C), Ad31 (species A), and Ad41 (species F) hardly bound to hematopoietic progenitor cells. Using a double-labeling system, we demonstrated that adenoviruses bind to quiescent CD34+ cells. Ad11p virions showed the highest affinity among the adenoviruses detected. We further confirmed that virus fiber-specific receptors were present on the hematopoietic progenitor cell surface, because both recombinant fiber of Ad11p and specific antiserum against rfiber could block virus attachment. The ability of the adenoviruses to infect hematopoietic cells was studied by immunofluorescence staining. The adenoviruses from species B and Ad37 showed higher infectivity than Ad31, Ad5, Ad4, and Ad41. Among the studied species B adenoviruses, Ad11p manifested a superior infectivity. Thus, we have confirmed that these cells have high-affinity receptors for species B:2 human adenovirus, Ad11p, and this virus may be used as candidate vector to target therapeutic genes to hematopoietic stem cells.
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