Abstract:
BACKGROUND:The liver fluke Opisthorchis viverrini is classified as a class I carcinogen due to the association between cholangiocarcinoma and chronic O. viverrini infection. During its feeding activity within the bile duct, the parasite secretes several cathepsin F cysteine proteases that may induce or contribute to the pathologies associated with hepatobiliary abnormalities. METHODOLOGY/PRINCIPAL FINDINGS:Here, we describe the cDNA, gene organization, phylogenetic relationships, immunolocalization, and functional characterization of the cathepsin F cysteine protease gene, here termed Ov-cf-1, from O. viverrini. The full length mRNA of 1020 nucleotides (nt) encoded a 326 amino acid zymogen consisting of a predicted signal peptide (18 amino acids, aa), prosegment (95 aa), and mature protease (213 aa). BLAST analysis using the Ov-CF-1 protein as the query revealed that the protease shared identity with cathepsin F-like cysteine proteases of other trematodes, including Clonorchis sinensis (81%), Paragonimus westermani (58%), Schistosoma mansoni and S. japonicum (52%), and with vertebrate cathepsin F (51%). Transcripts encoding the protease were detected in all developmental stages that parasitize the mammalian host. The Ov-cf-1 gene, of approximately 3 kb in length, included seven exons interrupted by six introns; the exons ranged from 69 to 267 bp in length, the introns from 43 to 1,060 bp. The six intron/exon boundaries of Ov-cf-1 were conserved with intron/exon boundaries in the human cathepsin F gene, although the gene structure of human cathepsin F is more complex. Unlike Ov-CF-1, human cathepsin F zymogen includes a cystatin domain in the prosegment region. Phylogenetic analysis revealed that the fluke, human, and other cathepsin Fs branched together in a clade discrete from the cathepsin L cysteine proteases. A recombinant Ov-CF-1 zymogen that displayed low-level activity was expressed in the yeast Pichia pastoris. Although the recombinant protease did not autocatalytically process and activate to a mature enzyme, trans-processing by Fasciola hepatica cathepsin L cleaved the prosegment of Ov-CF-1, releasing a mature cathepsin F with activity against the peptide Z-Phe-Arg-NHMec >50 times that of the zymogen. Immunocytochemistry using antibodies raised against the recombinant enzyme showed that Ov-CF-1 is expressed in the gut of the mature hermaphroditic fluke and also in the reproductive structures, including vitelline glands, egg, and testis. Ov-CF-1 was detected in bile duct epithelial cells surrounding the flukes several weeks after infection of hamsters with O. viverrini and, in addition, had accumulated in the secondary (small) bile ducts where flukes cannot reach due to their large size. CONCLUSIONS/SIGNIFICANCE:A cathepsin F cysteine protease of the human liver fluke O. viverrini has been characterized at the gene and protein level. Secretion of this protease may contribute to the hepatobiliary abnormalities, including cholangiocarcinogenesis, observed in individuals infected with this parasite.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Pinlaor P,Kaewpitoon N,Laha T,Sripa B,Kaewkes S,Morales ME,Mann VH,Parriott SK,Suttiprapa S,Robinson MW,To J,Dalton JP,Loukas A,Brindley PJdoi
10.1371/journal.pntd.0000398subject
Has Abstractpub_date
2009-01-01 00:00:00pages
e398issue
3eissn
1935-2727issn
1935-2735journal_volume
3pub_type
杂志文章abstract::Revealing the dispersal of dengue viruses (DENV) in time and space is central to understanding their epidemiology. However, the processes that shape DENV transmission patterns at the scale of local populations are not well understood, particularly the impact of such factors as human population movement and urbanizatio...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000766
更新日期:2010-07-27 00:00:00
abstract::Trypanosoma cruzi has been subdivided into seven Discrete Typing Units (DTUs), TcI-TcVI and Tcbat. Two major evolutionary models have been proposed to explain the origin of hybrid lineages, but while it is widely accepted that TcV and TcVI are the result of genetic exchange between TcII and TcIII strains, the origin o...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006139
更新日期:2017-12-18 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pntd.0006803.]. ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,已发布勘误
doi:10.1371/journal.pntd.0007150
更新日期:2019-02-26 00:00:00
abstract::Rabies is an ancient viral disease that significantly impacts human and animal health throughout the world. In the developing parts of the world, dog bites represent the highest risk of rabies infection to people, livestock, and other animals. However, in North America, where several rabies virus variants currently ci...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0005249
更新日期:2017-03-16 00:00:00
abstract::In French Guiana, from 1984 to 2011, 14 animal rabies cases and 1 human rabies case (2008) were diagnosed. In January 2011, vampire-bat attacks occurred in 2 isolated villages. In mid-January, a medical team from the Cayenne Centre for Anti-Rabies Treatment visited the sites to manage individuals potentially exposed t...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002258
更新日期:2013-06-27 00:00:00
abstract:BACKGROUND:The sensitivity and specificity of two in-house MAC-ELISA assays were tested and compared with the performance of commercially-available CTK lateral flow rapid test and EUROIMMUN IFA assays for the detection of anti-Chikungunya virus (CHIKV) IgM. Each MAC-ELISA assay used a whole virus-based antigen derived ...
journal_title:PLoS neglected tropical diseases
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doi:10.1371/journal.pntd.0000753
更新日期:2010-07-20 00:00:00
abstract::Zika virus was reported in the rainforest city of Iquitos, Peru in 2016. The potential associations between Zika and fetal neurological disorders were reported extensively in the media regarding neighboring Brazil, and led to great concern about the impact Zika could have on people's health in Iquitos when it arrived....
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006708
更新日期:2018-08-30 00:00:00
abstract::Bat rabies is an emerging disease of public health significance in the Americas. The Caribbean island of Trinidad experiences periodic outbreaks within the livestock population. We performed molecular characterisation of Trinidad rabies virus (RABV) and used a Bayesian phylogeographic approach to investigate the exten...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002365
更新日期:2013-08-22 00:00:00
abstract:BACKGROUND:Soil-transmitted helminth (STH) infection leads to malnutrition and anemia, and has been linked to impaired child development. Previous research on this topic is limited and mostly conducted in school-age children. The goal of this study was to determine the effect of the number of detected STH infections be...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0006688
更新日期:2018-07-27 00:00:00
abstract::Theileria parva is an economically important, intracellular, tick-transmitted parasite of cattle. A live vaccine against the parasite is effective against challenge from cattle-transmissible T. parva but not against genotypes originating from the African Cape buffalo, a major wildlife reservoir, prompting the need to ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
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journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001347
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:The neglected human diseases caused by trypanosomatids are currently treated with toxic therapy with limited efficacy. In search for novel anti-trypanosomatid agents, we showed previously that the Crotalus viridis viridis (Cvv) snake venom was active against infective forms of Trypanosoma cruzi. Here, we des...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003252
更新日期:2014-10-16 00:00:00
abstract:BACKGROUND:On the Zanzibar islands, United Republic of Tanzania, elimination of urogenital schistosomiasis is strived for in the coming years. This qualitative study aimed to better understand community knowledge, perceptions, and practices associated with schistosomiasis among school-aged children on Unguja and Pemba ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0004814
更新日期:2016-07-11 00:00:00
abstract:BACKGROUND:A majority infections caused by dengue virus (DENV) are asymptomatic, but a higher incidence of severe illness, such as dengue hemorrhagic fever, is associated with secondary infections, suggesting that pre-existing immunity plays a central role in dengue pathogenesis. Primary infections are typically associ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005395
更新日期:2017-02-21 00:00:00
abstract:BACKGROUND:Filarial nematodes, including Brugia malayi, the causative agent of lymphatic filariasis, undergo molting in both arthropod and mammalian hosts to complete their life cycles. An understanding of how these parasites cross developmental checkpoints may reveal potential targets for intervention. Pharmacological...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000625
更新日期:2010-03-09 00:00:00
abstract::Adenosine-5'-triphosphate (ATP) is an important phosphate metabolite abundantly found in Mycobacterium leprae bacilli. This pathogen does not derive ATP from its host but has its own mechanism for the generation of ATP. Interestingly, this molecule as well as several antigenic proteins act as bio-markers for the detec...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003661
更新日期:2015-03-26 00:00:00
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journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005982
更新日期:2017-10-02 00:00:00
abstract:BACKGROUND:Public health responses to outbreaks of dengue, chikungunya, and Zika virus have been stymied by the inability to control the primary vector, Aedes aegypti mosquitos. Consequently, the need for novel approaches to Aedes vector control is urgent. Placement of three autocidal gravid ovitraps (AGO traps) in ~85...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007538
更新日期:2019-07-25 00:00:00
abstract::(•)NO is considered to be a key macrophage-derived cytotoxic effector during Trypanosoma cruzi infection. On the other hand, the microbicidal properties of reactive oxygen species (ROS) are well recognized, but little importance has been attributed to them during in vivo infection with T. cruzi. In order to investigat...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001492
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:The main objective of the study was to determine the degree of sensitization to Anisakis spp. antigens in healthy coastal population of Dalmatia given the high thermally unprocessed fish intake rate present in this area, suggested as a significant risk factor for anisakiasis. We performed a monocenter, cross...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002673
更新日期:2014-02-06 00:00:00
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journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000326
更新日期:2008-01-01 00:00:00
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journal_title:PLoS neglected tropical diseases
pub_type: 临床试验,杂志文章
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journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008369
更新日期:2020-05-26 00:00:00
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journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002425
更新日期:2013-09-19 00:00:00
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journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0007901
更新日期:2020-01-30 00:00:00
abstract::The human gut has been continuously exposed to a broad spectrum of intestinal organisms, including viruses, bacteria, fungi, and parasites (protozoa and worms), over millions of years of coevolution, and plays a central role in human health. The modern lifestyles of Western countries, such as the adoption of highly hy...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,评审
doi:10.1371/journal.pntd.0005916
更新日期:2017-11-02 00:00:00
abstract::Disseminated disease from non-typhoidal Salmonella enterica strains results in >20% mortality globally. Barriers to effective treatment include emerging multidrug resistance, antibiotic treatment failure, and risk factors such as malnutrition and related micronutrient deficiencies. Individuals in sub-Saharan Africa ar...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0008737
更新日期:2020-10-02 00:00:00
abstract:BACKGROUND:Cutaneous dirofilariosis is a canine mosquito-borne zoonosis that can cause larva migrans disease in humans. Dirofilaria repens is considered an emerging pathogen occurring with high prevalence in Mediterranean areas and many parts of tropical Asia. In Hong Kong, a second species, Candidatus Dirofilaria hong...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0005028
更新日期:2016-10-11 00:00:00
abstract:BACKGROUND:Schistosome eggs must traverse tissues of the intestine or bladder to escape the human host and further the life cycle. Escape from host tissues is facilitated by secretion of immuno-reactive molecules by eggs and the formation of an intense strong granulomatous response by the host which acts to exclude the...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0000334
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Scabies is a disease of worldwide significance, causing considerable morbidity in both humans and other animals. The scabies mite Sarcoptes scabiei burrows into the skin of its host, obtaining nutrition from host skin and blood. Aspartic proteases mediate a range of diverse and essential physiological functi...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0002525
更新日期:2013-11-07 00:00:00