| 1. |
- Flodell, Sara, et al.
(författare)
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Solution structure of the apical stem-loop of the human hepatitis B virus encapsidation signal.
- 2006
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 34:16, s. 4449-4457
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV) replication is initiated by HBV RT binding to the highly conserved encapsidation signal, epsilon, at the 5' end of the RNA pregenome. Epsilon contains an apical stem-loop, whose residues are either totally conserved or show rare non-disruptive mutations. Here we present the structure of the apical stem-loop based on NOE, RDC and (1)H chemical shift NMR data. The (1)H chemical shifts proved to be crucial to define the loop conformation. The loop sequence 5'-CUGUGC-3' folds into a UGU triloop with a CG closing base pair and a bulged out C and hence forms a pseudo-triloop, a proposed protein recognition motif. In the UGU loop conformations most consistent with experimental data, the guanine nucleobase is located on the minor groove face and the two uracil bases on the major groove face. The underlying helix is disrupted by a conserved non-paired U bulge. This U bulge adopts multiple conformations, with the nucleobase being located either in the major groove or partially intercalated in the helix from the minor groove side, and bends the helical stem. The pseudo-triloop motif, together with the U bulge, may represent important anchor points for the initial recognition of epsilon by the viral RT.
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| 2. |
- Ingman, Mikael, et al.
(författare)
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Novel mutation in Hepatitis B virus preventing HBeAg production and resembling primate strains.
- 2006
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 87, s. 307-310
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Tidskriftsartikel (refereegranskat)abstract
- Chronic carriers of hepatitis B infection often harbour virus strains with mutations in the precore region. These mutations are temporally associated with the development of HBeAg loss and seroconversion to anti-HBe. The most common precore mutation is a stop codon at position 1896, but other mutations leading to abolished HBeAg secretion have been described. Here, a novel precore mutation introducing a lysine in the precore position 28, a sequence shared by non-human primates but not by other human isolates, is described. However, the insertion causes a frame-shift preventing the expression of HBeAg by introducing a stop codon 5 aa downstream of the mutation. Analysis of the predicted RNA secondary structure indicates that the insertion could occur without fatally affecting the stability of the stem–loop encapsidation signal.
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| 3. |
- Karlsson, Ulf, et al.
(författare)
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Mode of coreceptor use by R5 HIV type 1 correlates with disease stage: a study of paired plasma and cerebrospinal fluid isolates.
- 2009
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Ingår i: AIDS research and human retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 25:12, s. 1297-1305
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Tidskriftsartikel (refereegranskat)abstract
- Through the use of chimeric CXCR4/CCR5 receptors we have previously shown that CCR5-tropic (R5) HIV-1 isolates acquire a more flexible receptor use over time, and that this links to a reduced viral susceptibility to inhibition by the CCR5 ligand RANTES. These findings may have relevance with regards to the efficacy of antiretroviral compounds that target CCR5/virus interactions. Compartmentalized discrepancies in coreceptor use may occur, which could also affect the efficacy of these compounds at specific anatomical sites, such as within the CNS. In this cross-sectional study we have used wild-type CCR5 and CXCR4 as well as chimeric CXCR4/CCR5 receptors to characterize coreceptor use by paired plasma and cerebrospinal fluid (CSF) isolates from 28 HIV-1-infected individuals. Furthermore, selected R5 isolates, with varying chimeric receptor use, were tested for sensitivity to inhibition by the CCR5 antagonist TAK-779. Discordant CSF/plasma virus coreceptor use was found in 10/28 patients. Low CD4+ T cell counts correlated strongly with a more flexible mode of R5 virus CCR5 usage, as disclosed by an increased ability to utilize chimeric CXCR4/CCR5 receptors, specifically receptor FC-2. Importantly, an elevated ability to utilize chimeric receptors correlated with a reduced susceptibility to inhibition by TAK-779. Our findings show that a discordant CSF and plasma virus coreceptor use is not uncommon. Furthermore, we provide support for an emerging paradigm, where the acquisition of a more flexible mode of CCR5 usage is a key event in R5 virus pathogenesis. This may, in turn, negatively impact the efficacy of CCR5 antagonist treatment in late stage HIV-1 disease.
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| 4. |
- Kidd-Ljunggren, Karin, et al.
(författare)
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High levels of hepatitis B virus DNA in body fluids from chronic carriers.
- 2006
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Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701. ; 64:4, s. 352-357
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Tidskriftsartikel (refereegranskat)abstract
- infection with hepatitis B virus (HBV) is a major global health problem. Transmission is mainly blood-borne, although the route of infection during horizontal transmission in childhood is unclear. Nosocomial outbreaks of HBV have been widely reported, but have mainly focused on blood-borne transmission. There is Limited knowledge of the viral Load Levels in other body fluids. In the present study, chronic HBV carriers were tested for the presence of HBV DNA in serum, saliva, nasopharyngeal fluid, urine and tears by means of qualitative and quantitative polymerase chain reaction (PCR) methods. Twenty-five patients who were positive for HBV DNA with both PCRs were included. Low titres in real-time PCR corresponded with weak bands in the qualitative assay. HBV DNA was found in two urine samples, 10 saliva samples, five nasopharyngeal, swabs and in tear fluid from four patients. One highly viraemic HBeAg-positive carrier with serum HBV DNA Levels of 7 x 10(9) genome copies had high copy numbers detected in both saliva and nasopharyngeal fluid. These results demonstrate that highly viraemic HBV carriers may have high titres of HBV DNA in other body fluids. This has particular importance for infection control programmes and regulations, underlining the importance of aiming towards regular HBV DNA testing and thus infectivity assessment of chronic carriers in order to prevent transmission. (c) 2006 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
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| 5. |
- Petzold, Katja, 1981-, et al.
(författare)
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Conserved nucleotides in an RNA essential for hepatitis B virus replication show distinct mobility patterns.
- 2007
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 35:20, s. 6854-6861
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Tidskriftsartikel (refereegranskat)abstract
- The number of regulatory RNAs with identified non-canonical structures is increasing, and structural transitions often play a role in their biological function. This stimulates interest in internal motions of RNA, which can underlie structural transitions. Heteronuclear NMR relaxation measurements, which are commonly used to study internal motion, only report on local motions of few sites within the molecule. Here we have studied a 27-nt segment of the human hepatitis B virus (HBV) pregenomic RNA, which is essential for viral replication. We combined heteronuclear relaxation with the new off-resonance ROESY technique, which reports on internal motions of H,H contacts. Using off-resonance ROESY, we could for the first time detect motion of through-space H,H contacts, such as in intra-residue base-ribose contacts or inter-nucleotide contacts, both essential for NMR structure determination. Motions in non-canonical structure elements were found primarily on the sub-nanosecond timescale. Different patterns of mobility were observed among several mobile nucleotides. The most mobile nucleotides are highly conserved among different HBV strains, suggesting that their mobility patterns may be necessary for the RNA’s biological function.
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