A natural inter-genotypic (2b/1b) recombinant of hepatitis C virus in the Philippines

Kageyama, Seiji; Agdamag, Dorothy M.; Alesna, Evelyn T.; Leano, Prisca Susan A.; Heredia, Anna Marie L.; Abellanosa-Tac-An, Ilya P.; Jereza, Lourdes D.; Tanimoto, Tomoaki; Yamamura, Jun-ichi; Ishiguro, Hiroshi

doi:10.1002/jmv.20714

Cited by 79 publications

(64 citation statements)

References 33 publications

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“…Additionally, at least ten other different intergenotypic recombinant forms (RFs) of HCV have been described and are totally or partially characterised (Table 1). Within this group of recombinants, we can observe the presence of recombinant forms between genotypes 2 and 6 described in Vietnam [130] and Taiwan [131] , between genotypes 2 and 5 described in France [132] , between genotypes 3 and 1 in Taiwan [131] and China [133] , and between genotypes 2 and 1 reported in Japan, the United States and the Philippines [134][135][136][137] . It is interesting to note that recombinant forms found so far have a wide geographic distribution.…”

Section: Recombinationmentioning

confidence: 85%

“…Finally, despite recombination events between different genotypes/subtypes co-infecting the same patient are probably easier to detect, they are less likely to occur, since the strains of different subtypes differ more between them than between those from the same subtype; this would imply a lower probability of template switching and moreover, if a recombination event does indeed happen, it will likely generate recombinant sequences less viable than the parental ones. Some or even all these factors acting in concert might explain why the frequency of recombinant HCV sequences reported to date is so low [49,111,[124][125][126][127][128][129][130][131][132][133][134][135][136][137][140][141][142][143][144][145][146][147] . How relevant recombination for HCV long term evolution and its incidence in HCV infection is, has not been thoroughly investigated yet, but these findings support a potentially significant role for recombination by creating genetic variation through the reshuffling of independent variants [146] .…”

Section: Recombinationmentioning

confidence: 99%

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Hepatitis C virus genetic variability and evolution

Echeverría

Moratorio

Cristina

et al. 2015

WJH

101

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Hepatitis C virus (HCV) has infected over 170 million people worldwide and creates a huge disease burden due to chronic, progressive liver disease. HCV is a singlestranded, positive sense, RNA virus, member of the Flaviviridae family. The high error rate of RNA-dependent RNA polymerase and the pressure exerted by the host immune system, has driven the evolution of HCV into 7 different genotypes and more than 67 subtypes. HCV evolves by means of different mechanisms of genetic variation. On the one hand, its high mutation rates generate the production of a large number of different but closely related viral variants during infection, usually referred to as a quasispecies. The great quasispecies variability of HCV has also therapeutic implications since the continuous generation and selection of resistant or fitter variants within the quasispecies spectrum might allow viruses to escape control by antiviral drugs. On the other hand HCV exploits recombination to ensure its survival. This enormous viral diversity together with some host factors has made it difficult to control viral dispersal. Current treatment options involve pegylated interferon-α and ribavirin as dual therapy or in combination with a direct-acting antiviral drug, depending on the country. Despite all the efforts put into antiviral therapy studies, eradication of the virus or the development of a preventive vaccine has been unsuccessful so far. This review focuses on current available data reported to date on the genetic mechanisms driving the molecular evolution of HCV populations and its relation with the antiviral therapies designed to control HCV infection. Hepatitis C virus genetic variability and evolution no preventive vaccine, and though antiviral therapy has been improved in the past few years, not all patients eradicate the virus as a result of it. The main reason lies in the intrinsic genetic variability that characterises RNA viruses, such as HCV, whose RNA polymerase lacks proof-reading activity, leading to a high mutation rate and the generation of a wide range of genome variants better known as a quasispecies. Therefore this review summarises current data on HCV quasispecies dynamics, antiviral therapy and recombination events.Echeverría N, Moratorio G, Cristina J, Moreno P. Hepatitis C virus genetic variability and evolution. World J Hepatol 2015; 7(6): 831845 Available from:

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Section: Recombinationmentioning

confidence: 85%

Section: Recombinationmentioning

confidence: 99%

Hepatitis C virus genetic variability and evolution

Echeverría

Moratorio

Cristina

et al. 2015

WJH

101

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“…Because of this huge genetic diversity, HCV is currently classified into six major genotypes and more than 80 subtypes (44). Recombination may be another mechanism exploited by HCV to increase genetic diversity: naturally occurring intergenotypic recombinant viruses that often have their recombination points in the trans-membrane domains of NS2 were recently identified (20,21,26,27,33,35).Recent publications have reported the presence of natural HCV subgenomic RNAs in serum and liver of infected patients, mostly containing large in-frame deletions from E1 up to NS2, always found together with the full-length wild-type (wt) RNAs (5,16,36,54). These mutant viral genomes persist for a long time (at least 2 years), and sequence analysis suggests that subgenomic (the predominant species during this period) and full-length HCV evolve independently (54).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Naturally Occurring Hepatitis C Virus Subgenomic Deletion Mutants Replicate Efficiently in Huh-7 Cells and Are trans -Packaged In Vitro To Generate Infectious Defective Particles

Pacini¹,

Graziani²,

Bartholomew³

et al. 2009

J Virol

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Naturally occurring hepatitis C virus (HCV) subgenomic RNAs have been found in several HCV patients. These subgenomic deletion mutants, mostly lacking the genes encoding envelope glycoproteins, were found in both liver and serum, where their relatively high abundance suggests that they are capable of autonomous replication and can be packaged and secreted in viral particles, presumably harboring the envelope proteins from wild type virus coinfecting the same cell. We recapitulated some of these natural subgenomic deletions in the context of the isolate JFH-1 and confirmed these hypotheses in vitro. In Huh-7.5 cells, these deletioncontaining genomes show robust replication and can be efficiently trans-packaged and infect naïve Huh-7.5 cells when cotransfected with the full-length wild-type J6/JFH genome. The genome structure of these natural subgenomic deletion mutants was dissected, and the maintenance of both core and NS2 regions was proven to be significant for efficient replication and trans-packaging. To further explore the requirements needed to achieve trans-complementation, we provided different combinations of structural proteins in trans. Optimal trans-complementation was obtained when fragments of the polyprotein encompassing core to p7 or E1 to NS2 were expressed. Finally, we generated a stable helper cell line, constitutively expressing the structural proteins from core to p7, which efficiently supports trans-complementation of a subgenomic deletion encompassing amino acids 284 to 732. This cell line can produce and be infected by defective particles, thus representing a powerful tool to investigate the life cycle and relevance of natural HCV subgenomic deletion mutants in vivo.Hepatitis C virus (HCV) is an enveloped virus belonging to the family Flaviviridae. The virus genome is a positive-stranded RNA of about 9,600 nucleotides, which contains a single open reading frame (ORF) encoding both structural (core, E1, E2, and p7) and nonstructural (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) proteins (47). Two highly conserved untranslated regions (UTRs) are found at the 5Ј and 3Ј ends, which play critical roles in both viral translation and replication (13,14,23).HCV is estimated to infect 170 million people worldwide (1, 43) and in a high percentage of individuals causes a chronic liver infection that frequently evolves into an array of diseases, including cirrhosis (12, 15, 38) and hepatocellular carcinoma (4,7,17,30,38,49).The HCV RNA-dependent RNA polymerase (NS5B) has a high frequency of incorrect nucleotide insertions, in the range of 10 Ϫ4 to 10 Ϫ5 base substitutions per site, which can result in the rapid generation of HCV quasispecies (37, 45). Because of this huge genetic diversity, HCV is currently classified into six major genotypes and more than 80 subtypes (44). Recombination may be another mechanism exploited by HCV to increase genetic diversity: naturally occurring intergenotypic recombinant viruses that often have their recombination points in the trans-membrane domains of NS2 were recently i...

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“…Впервые рекомбинант 2b/1b был вы-явлен в 2006 г. на Филиппинах, затем в 2011 и 2012 гг. в Японии [38][39][40]. При этом, согласно точке рекомбинации, все эти межгенотипные рекомбинанты были сформирова-ны в результате различных рекомбинационных событий, как и еще 4 подобных рекомбинанта, идентифицирован-ных в 2014 г. в США.…”

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Phylodynamic of HCV Populations

Kalinina

2015

Annals RAMS

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Hepatitis C virus is an actual public health problem worldwide since its discovering in 1989. It is explained not only by the wide spreading and frequent adverse outcomes of disease, the lack of effective preventive vaccine, but also by the high genetic variability of the virus. The current review summarizes the results of phylodynamic and phylogeographic studies of different HCV populations that allowed to characterize epidemic processes, to analyze the divergence of HCV into genotypes and subtypes, and to determine the geographic origin of the current HCV epidemic variants.Key words hepatitis C virus, phylodinamic, evolution, genotypes, recombinant forms. 574ВЕСТНИК РАМН /2015/ 70 (5) вых инструментариев и игл как в индустриально развитых странах, так и в развивающихся, а популяции субтипа 1а, продлившийся также до 80-х гг., -масштабным внутри-венным использованием психотропных средств в странах Северной Америки, Европы, в Англии и Австралии [4,6,7]. Последующее замедление темпов роста обеих по-пуляций еще до открытия в 1989 г. самого возбудителя ни-А-ни-B гепатита произошло в связи с внедрением технологий скрининга образцов донорской крови на на-личие австралийского антигена, вируса иммунодефици-та человека, инактивации факторов свертывания крови, а также в связи с более тщательным соблюдением мер профилактики при различных парентеральных меди-цинских вмешательствах, использованием одноразовых шприцев [5,6]. Схожая филодинамика популяций 1а и 1b просле-живается при моделировании развития локальных эпи-демий. По данным O.G. Pybus и соавт., в Англии неэк-споненциальный рост популяции субтипа 1а продлился до 40-х гг. Переход к экспоненциальному росту совпал с трехкратным внедрением вариантов ВГС субтипа 1а на территорию Англии в когорту людей, начавших упо-треблять опиаты внутривенно [8]. В странах Средизем-номорья (Греция, Турция, Кипр) развитие эпидемии субтипа 1b началось в первые десятилетия ХХ в. с Греции, в 1920-1930-е гг. она распространилась на соседние стра-ны -Турцию и Кипр [9]. В Турции экспоненциальный рост популяции субтипа 1b происходил в 1940-1999-х гг. за счет распространения изолятов, циркулировавших ис-ключительно внутри страны, в основном при проведении различных парентеральных медицинских манипуляций, в результате чего турецкие изоляты субтипа 1b сформи-ровали четкую монофилитическую группу, отличную от изолятов соседних стран Средиземноморья [9].Анализ полноразмерных геномов 7 субтипов ВГС ге-нотипа 1 (1a, 1b, 1c, 1e, 1g, 1h, 1l), идентифицированных на территории Камеруна, позволил предположить, что именно эта страна является регионом происхождения вариантов ВГС генотипа 1 [10].В отличие от субтипов 1а и 1b движущей силой гло-бальной дессиминации генотипа 2 стали трансатлантиче-ская работорговля, при которой было перемещено около 17 млн человек из стран Западной Африки в Северную и Южную Америку, и колониальная политика европейских стран, охватившая африканский континент и азиатские страны [11,12]. В период 1700-1850 гг. установлен мно-жественный вброс генотипа 2 с территории Ганы и Бе-н...

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A natural inter-genotypic (2b/1b) recombinant of hepatitis C virus in the Philippines

Cited by 79 publications

References 33 publications

Hepatitis C virus genetic variability and evolution

Hepatitis C virus genetic variability and evolution

Naturally Occurring Hepatitis C Virus Subgenomic Deletion Mutants Replicate Efficiently in Huh-7 Cells and Are trans -Packaged In Vitro To Generate Infectious Defective Particles

Phylodynamic of HCV Populations

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