11 results on '"Hall, William W."'
Search Results
2. A Multicentre Molecular Analysis of Hepatitis B and Blood-Borne Virus Coinfections in Viet Nam.
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Dunford, Linda, Carr, Michael J., Dean, Jonathan, Linh Thuy Nguyen, Thu Hong Ta Thi, Binh Thanh Nguyen, Connel, Jeff, Coughlan, Suzie, Hien Tran Nguyen, Hall, William W., and Lan Anh Nguyen Thi
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HIV infections ,DISEASES ,LENTIVIRUS diseases ,SEXUALLY transmitted diseases ,HIV ,HIV-positive persons - Abstract
Hepatitis B (HBV) infection is endemic in Viet Nam, with up to 8.4 million individuals estimated to be chronically infected. We describe results of a large, multicentre seroepidemiological and molecular study of the prevalence of HBV infection and blood-borne viral coinfections in Viet Nam. Individuals with varying risk factors for infection (n = 8654) were recruited from five centres; Ha Noi, Hai Phong, Da Nang, Khanh Hoa and Can Tho. A mean prevalence rate of 10.7% was observed and levels of HBsAg were significantly higher in injecting drug users (IDUs) (17.4%, n = 174/1000) and dialysis patients (14.3%, n = 82/575) than in lower-risk groups (9.4%; p<0.001). Coinfection with HIV was seen in 28% of HBV-infected IDUs (n = 49/ 174) and 15.2% of commercial sex workers (CSWs; n = 15/99). HCV infection was present in 89.8% of the HBV-HIV coinfected IDUs (n = 44/49) and 40% of HBV-HIV coinfected CSWs (n = 16/40). Anti-HDV was detected in 10.7% (n = 34/318) of HBsAg positive individuals. Phylogenetic analysis of HBV S gene (n = 187) showed a predominance of genotype B4 (82.6%); genotypes C1 (14.6%), B2 (2.7%) and C5 (0.5%) were also identified. The precore mutation G1896A was identified in 35% of all specimens, and was more frequently observed in genotype B (41%) than genotype C (3%; p<0.0001). In the immunodominant 'a' region of the surface gene, point mutations were identified in 31% (n = 58/187) of sequences, and 2.2% (n = 4/187) and 5.3% (n = 10/187) specimens contained the major vaccine escape mutations G145A/R and P120L/Q/S/T, respectively. 368 HBsAg positive individuals were genotyped for the IL28B SNP rs12979860 and no significant association between the IL28B SNP and clearance of HBsAg, HBV viral load or HBeAg was observed. This study confirms the high prevalence of HBV infection in Viet Nam and also highlights the significant levels of blood-borne virus coinfections, which have important implications for hepatitis-related morbidity and development of effective management strategies. [ABSTRACT FROM AUTHOR]
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- 2012
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3. Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import.
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Lili Gu, Tsuji, Takahiro, Jarboui, Mohamed Ali, Yeo, Geok P., Sheehy, Noreen, Hall, William W., and Gautier, Virginie W.
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HIV infections ,VIRAL replication ,NUCLEAR nonproliferation ,HIV ,PEPTIDES - Abstract
Background: The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s) predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised. Results: In our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein) as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportinmediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion. Conclusions: Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy. [ABSTRACT FROM AUTHOR]
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- 2011
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4. Covalent bonded Gag multimers in human immunodeficiency virus type-1 particles.
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Kitagawa, Yoshinori, Maeda-Sato, Masae, Tanaka, Keiko, Tobiume, Minoru, Sawa, Hirofumi, Hasegawa, Hideki, Kojima, Asato, Hall, William W., Kurata, Takeshi, Sata, Tetsutaro, and Takahashi, Hidehiro
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CELL membranes ,HIV ,RNA ,VIRAL genomes ,ELECTRON microscopic diagnosis - Abstract
The oligomerization of HIV-1 Gag and Gag-Pol proteins, which are assembled at the plasma membrane, leads to viral budding. The budding generally places the viral components under non-reducing conditions. Here the effects of non-reducing conditions on Gag structures and viral RNA protection were examined. Using different reducing conditions and SDS-PAGE, it was shown that oligomerized Gag possesses intermolecular covalent bonds under non-reducing conditions. In addition, it was demonstrated that the mature viral core contains a large amount of covalent bonded Gag multimers, as does the immature core. Viral genomic RNA becomes sensitive to ribonuclease in reducing conditions. These results suggest that, under non-reducing conditions, covalent bonded Gag multimers are formed within the viral particles and play a role in protection of the viral genome. [ABSTRACT FROM AUTHOR]
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- 2009
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5. Absence of cytomegalovirus infection in children with acquired immunodeficiency syndrome and distal sensory polyneuropathy.
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De Q. C. Araújo, Alexandra P., Couglan, Suzie, and Hall, William W.
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CYTOMEGALOVIRUS diseases ,AIDS in children ,NEUROPATHY ,BLOOD plasma ,POLYMERASE chain reaction ,CYTOMEGALIC inclusion disease - Abstract
To investigate the role of cytomegalovirus (CMV) infection in the pathogenesis of peripheral neuropathy in children with acquired immunodeficiency syndrome (AIDS) a crosssectional descriptive study was conducted on a sample of nine children. Plasma samples were tested for CMV DNA by two polymerase chain reaction assays (sensitivity limits of 400 and 10 copies/mls) respectively. While all nine were CMV seropositive all were negative for viremia in both assays. CMV would appear not to be involved in children with AIDS-associated sensory neuropathies. [ABSTRACT FROM AUTHOR]
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- 2004
6. THE ROLE OF TOPOISOMERASE I IN HIV-1 REPLICATION.
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TAKAHASHI, Hidehiro, TATSUMI, Masashi, MATSUDA, Michiyuki, NAGASHIMA, Kazuo, KURATA, Takeshi, and HALL, William W.
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DNA topoisomerase I ,HIV ,VIRAL replication ,DNA synthesis ,GENETIC transcription - Abstract
The mechanisms involved in the restriction of the cellular tropism of HIV-1 to cells of primate origin remain to be clearly defined. However, a number of studies have shown that this is determined not only at the level of the cellular receptor(s) or virus entry, but at a number of additional and later stages in virus replication. We have recently reported that the reverse transcription of HIV-1 RNA is markedly enhanced by the association of the gag encoded nucleocapsid p15 protein and cellular topoisomerase I. In the present study we have investigated if the recruitment of cellular topoisomerase 1 during virus replication is important in determining the cellular tropism of HIV-1. Employing a stable murine cell line, L929, expressing both human CD4 and topoisomerase I, it could be demonstrated that effective proviral DNA synthesis occurred following infection. In contrast in cells expressing only human CD4, proviral DNA synthesis was not detected. In addition we have co-expressed fusin, a protein known to act as an accessory factor as the virus entry stage in infection of T cell tropic HIV-1, to support viral entry completely. However no progeny virus could be detected after HIV-1 infection. These results suggest that reverse transcription in vivo is critically dependent on the presence of cellular topoisomerase I, and support the view that involvement of this enzyme is important in HIV-1 replication. Moreover the findings suggest that other factors which remained to be identified, are involved in restricting HIV-1 replication in non-primate cells. [ABSTRACT FROM AUTHOR]
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- 1997
7. Impaired protective role of HLA-B*57:01/58:01 in HIV-1 CRF01_AE infection: a cohort study in Vietnam.
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Minh, Tam Tran Thi, Hikichi, Yuta, Miki, Shoji, Imanari, Yuriko, Kusagawa, Shigeru, Okazaki, Midori, Thu, Thao Dang Thi, Shiino, Teiichiro, Matsuoka, Saori, Yamamoto, Hiroyuki, Ohashi, Jun, Hall, William W., Matano, Tetsuro, Thi, Lan Anh Nguyen, and Kawana-Tachikawa, Ai
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HIV , *HLA histocompatibility antigens , *VIETNAMESE people , *VIRAL load , *T cells - Abstract
• The protective effect of HLA-B*57:01/58:01 on HIV-1 CRF01_AE infection was examined. • The protective impact is impaired against CRF01_AE infection. • TW10-specific CD8+ T cells select for T242N even in CRF01_AE with viral fitness cost. • Less non-TW10 epitope presentation may contribute to the impaired protective impact. Human Leukocyte Antigen HLA-B*57:01 and B*58:01 are considered anti-HIV-1 protective alleles. HLA-B*57:01/58:01-restricted HIV-1 Gag TW10 (TSTLQEQIGW, Gag residues 240-249) epitope-specific CD8+ T cell responses that frequently select for a Gag escape mutation, T242N, with viral fitness cost are crucial for HIV-1 control. Although this finding has been observed in cohorts where HIV-1 subtype B or C predominates, the protective impact of HLA-B*57:01/58:01 has not been reported in Southeast Asian countries where HIV-1 CRF01_AE is the major circulating strain. Here, the effect of HLA-B*57:01/58:01 on CRF01_AE infection was investigated. The correlation of HLA-B*57:01/58:01 with viral load and CD4 counts were analyzed in the CRF01_AE-infected Vietnamese cohort (N = 280). The impact of the T242N mutation on CRF01_AE replication capacity was assessed. HLA-B*57:01/58:01 -positive individuals mostly had HIV-1 with T242N (62/63) but showed neither a significant reduction in viral load nor increased CD4 counts relative to B*57:01/58:01 -negative participants. In vitro and in vivo analyses revealed a significant reduction in viral fitness of CRF01_AE with T242N. In silico analysis indicated reduced presentation of epitopes in the context of CRF01_AE compared to subtype B or C in 10/16 HLA-B*57:01/58:01-restricted HIV-1 epitopes. The protective impact of HLA-B*57:01/58:01 on CRF01_AE infection is impaired despite strong suppressive pressure by TW10-specific CD8+ T cells. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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8. CD8+ T cell-based strong selective pressure on multiple simian immunodeficiency virus targets in macaques possessing a protective MHC class I haplotype.
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Hau, Trang Thi Thu, Nakamura-Hoshi, Midori, Kanno, Yoshiaki, Nomura, Takushi, Nishizawa, Masako, Seki, Sayuri, Ishii, Hiroshi, Kawana-Tachikawa, Ai, Hall, William W., Nguyen Thi, Lan Anh, Matano, Tetsuro, and Yamamoto, Hiroyuki
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SIMIAN immunodeficiency virus , *VIRAL genomes , *MAJOR histocompatibility complex , *MACAQUES , *VIRAL mutation , *RHESUS monkeys , *VIRAL antigens - Abstract
In human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections, host major histocompatibility complex class I (MHC-I) genotypes have a great impact on viral replication and MHC-I-associated viral genome mutations are selected under CD8+ T-cell pressure. Association of MHC-I genotypes with HIV/SIV control has been investigated at MHC-I allele levels but not fully at haplotype levels. We previously established groups of rhesus macaques sharing individual MHC-I haplotypes. In the present study, we compared viral genome diversification after SIV infection in macaques possessing a protective MHC-I haplotype, 90-010-Id , with those possessing a non-protective MHC-I haplotype, 90-010-Ie. These two MHC-I haplotypes are associated with immunodominant CD8+ T-cell responses targeting similar regions of viral Nef antigen. Analyses of viral genome sequences and antigen-specific T-cell responses showed four and two candidates of viral CD8+ T-cell targets associated with 90-010-Id and 90-010-Ie , respectively, in addition to the Nef targets. In these CD8+ T-cell target regions, higher numbers of mutations were detected at the setpoint after SIV infection in macaques possessing 90-010-Id than those possessing 90-010-Ie. These results indicate higher selective pressure on overall CD8+ T-cell targets associated with the protective MHC-I haplotype, suggesting a pattern of HIV/SIV control by multiple target-specific CD8+ T-cell responses. • Impact of MHC-I haplotypes on HIV/SIV replication was not fully examined. • We examined SIV mutations associated with a protective MHC-I haplotype. • Higher overall protective MHC-I haplotype-associated selective pressure was shown. • Study contributes to understanding of a CD8+ T cell-based HIV control mechanism. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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9. Tristetraprolin inhibits HIV-1 production by binding to genomic RNA
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Maeda, Masae, Sawa, Hirofumi, Tobiume, Minoru, Tokunaga, Kenzo, Hasegawa, Hideki, Ichinohe, Takeshi, Sata, Tetsutaro, Moriyama, Masami, Hall, William W., Kurata, Takeshi, and Takahashi, Hidehiro
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AIDS prevention , *HIV infections , *HIV , *IMMUNODEFICIENCY - Abstract
Abstract: HIV-1 genome has an AU-rich sequence and requires rapid nuclear export by Rev activity to prevent multiple splicing. HIV-1 infection occurs in activated CD4+ T cells where the decay of mRNAs of cytokines and chemokines is regulated by the binding of AU-rich elements to the mRNA-destabilizing protein tristetraprolin. We here investigated the influence of tristetraprolin on the replication of HIV-1. Treatment of siRNA against tristetraprolin in a latently HIV-1 infected cell line increases HIV-1 production following stimulation. A chloramphenicol acetyltransferase and luciferase assay revealed that exogenous tristetraprolin reduced HIV-1 virion production and in contrast increased the multiply spliced products. Furthermore, quantitative RT–PCR analysis showed tristetraprolin increases the ratio of multiple-spliced RNAs to un-, single-spliced RNA. Moreover, an electrophoretic mobility shift assay showed that tristetraprolin binds to synthesized HIV-1 RNA with AU-rich sequence but not to RNA with less AU sequence. These results suggest that tristetraprolin is a regulator of HIV-1 replication and enhances splicing by direct binding to AU-rich sequence of HIV-1 RNAs. [Copyright &y& Elsevier]
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- 2006
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10. Binding and dissociation of human topoisomerase I with hairpin-loop RNAs: implications for the regulation of HIV-1 replication
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Takahashi, Hidehiro, Sawa, Hirofumi, Hasegawa, Hideki, Sata, Tetsutaro, Hall, William W., and Kurata, Takeshi
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DNA topoisomerase I , *HIV , *ADENOSINE triphosphate - Abstract
Cellular topoisomerase I has been reported to be present in retroviral particles and to enhance viral cDNA synthesis; however, the mechanisms involved remain unknown. In the present study, it has been demonstrated that human topoisomerase I combines with a stem-loop RNA and that the bound topoisomerase I can be dissociated from RNA substrates in the presence of ATP. In addition, in vitro cleaved synthetic RNA bound by topoisomerase I is subsequently religated when the topoisomerase I is dissociated by ATP. A mechanism is proposed in which human topoisomerase I is carried into virions and regulates the repair of genomic RNA by its ligation activity. [Copyright &y& Elsevier]
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- 2002
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11. Reconstitution of cleavage of human immunodeficiency virus type-1 (HIV-1) RNAs
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Takahashi, Hidehiro, Sawa, Hirofumi, Hasegawa, Hideki, Sata, Tetsutaro, Hall, William W., Nagashima, Kazuo, and Kurata, Takeshi
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HIV , *MOLECULAR genetics - Abstract
A human immunodeficiency virus type 1 (HIV-1) particle contains approximately 1200 molecules of gag proteins and two copies of a 9.2-kb genomic RNA which has been reported to be dimerized and rapidly cleaved and to form a complex with a nucleocapsid protein, p7 (NCp7), during viral budding. These suggest that the cleavage can be reconstituted with gag proteins in vitro. Here we show that the
p15gag coding region of viral RNA is fragmented in viral particles and that in vitro-synthesized RNA transcripts of HIV-1 undergo cleavage which is activated by NCp7 and other factors. Single-stranded oligoribonucleotides were cleaved between C and A or U and A, leaving2′ ,3′ -cyclic phosphate and5′ -hydroxyl termini. These findings might explain the rapid degradation of genomic RNAs in HIV-1 particles. [Copyright &y& Elsevier]- Published
- 2002
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