Development of a second generation prophylactic vaccine against human papillomavirus

Human papillomaviruses (HPV) are the etiologic agent for cervical cancer (CC), the second cause of cancer death in women worldwide. It is estimated that half a million new cases are diagnosed each year, mostly in developing countries due to the lack of massive programs for early detection of the virus. Recently, two prophylactic vaccines against the main oncogenic HPV types 16 and 18 (responsible for 80% of CC) have been introduced into market. Both of these vaccines, obtained as recombinants, have been shown to be safe and effective; however, their high cost works against its immediate impact in the incidence of HPV infection in developing and low-income countries. There is a need to have in hand second generation, low cost vaccines of massive use that will decrease CC cases in a large extent. With this in mind, we have developed a recombinant expression platform that allows us to obtain virus-like particles (VLPs) to formulate both effective and accessible vaccines against HPV infection.Human papillomaviruses (HPV) are the etiologic agent for cervical cancer (CC), the second cause of cancer death in women worldwide. It is estimated that half a million new cases are diagnosed each year, mostly in developing countries due to the lack of massive programs for early detection of the virus. Recently, two prophylactic vaccines against the main oncogenic HPV types 16 and 18 (responsible for 80% of CC) have been introduced into market. Both of these vaccines, obtained as recombinants, have been shown to be safe and effective; however, their high cost works against its immediate impact in the incidence of HPV infection in developing and low-income countries. There is a need to have in hand second generation, low cost vaccines of massive use that will decrease CC cases in a large extent. With this in mind, we have developed a recombinant expression platform that allows us to obtain virus-like particles (VLPs) to formulate both effective and accessible vaccines against HPV infection.Fil: Alonso, Leonardo Gabriel. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Xbio S.a; ArgentinaFil: Cerutti, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. Xbio S.a; ArgentinaFil: Risso, Marikena Guadalupe. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Xbio S.a; ArgentinaFil: González, Mariángeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. Xbio S.a; ArgentinaFil: Camporeale, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentin

Development of a low-cost copro-LAMP assay for simultaneous copro-detection of Toxocara canis and Toxocara cati

Toxocariasis is a zoonotic disease caused mainly by Toxocara canis and Toxocara cati and diagnosis in dogs and cats is an important tool for its control. For this reason, a new coprological loop-mediated isothermal amplification (LAMP) assay was developed for the simultaneous detection of these species. The primer set was designed on a region of the mitochondrial cox-1 gene. Amplification conditions were evaluated using a temperature gradient (52°C to 68°C), different incubation times (15-120 min), and different concentrations of malachite green dye (0.004-0.4% w/v). The analytical sensitivity was evaluated with serial dilutions of genomic DNA from T. canis and T. cati adult worms, and with serial dilutions of DNA extracted from feces using a low-cost in-house method. The specificity was evaluated using genomic DNA from Canis lupus familiaris, Felis catus, Escherichia coli, Toxascaris leonina, Ancylostoma caninum, Echinococcus granulosus sensu stricto and Taenia hydatigena. The LAMP assay applied to environmental fecal samples from an endemic area showed an analytical sensitivity of 10-100 fg of genomic DNA and 10-5 serial dilutions of DNA extracted from feces using the low-cost in-house method; with a specificity of 100%. Additionally, the total development of the assay was carried out in a basic laboratory and per-reaction reagent cost decreased by ~80%. This new, low-cost tool can help identify the most common agents of toxocariasis in endemic areas in order to manage prevention strategies without having to rely on a laboratory with sophisticated equipment.Fil: Avila, Héctor Gabriel. Universidad Católica de Cuyo. Facultad de Ciencias Químicas y Tecnológicas. Laboratorio Provincial de Zoonosis Provincial; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; ArgentinaFil: Risso, Marikena Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Ruybal, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Repetto, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Butti, Marcos Javier. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Microbiología. Laboratorio de Parasitosis Humanas y Zoonosis Parasitarias; ArgentinaFil: Trangoni, Marcos David. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; ArgentinaFil: Grune Loffler, Sylvia. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología Veterinaria - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Patobiología Veterinaria; ArgentinaFil: Perez, Veronica Mirtha. Gobierno de la Provincia de San Juan. Ministerio de Salud Publica. Direccion de Epidemiologia. Seccion Rabia y Zoonosis.; ArgentinaFil: Periago, Maria Victoria. Fundación Mundo Sano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

First identification of Strongyloides stercoralis infection in a pet dog in Argentina, using integrated diagnostic approaches

Background: Strongyloides stercoralis is a soil-transmitted intestinal nematode with a complex life cycle that primarily affects humans, non-human primates, dogs, and occasionally cats. This study presents, to the best of our knowledge, the first case of S. stercoralis infection and its genotyping in a domestic dog from Argentina. Methods: The patient was a female wired-haired Teckel dog exhibiting recurrent coughing. Coproparasitological analysis using the Baermann technique revealed the presence of rhabditiform larvae morphologically compatible with S. stercoralis. To confirm this finding, molecular diagnosis (18S ribosomal RNA) and analysis of the cox1 gene were performed. Results: We identified a haplotype (HP20) that has previously only been related to S. stercoralis infection in dogs, but was found in the present study to be highly related to the haplotype (HP16) of a zoonotic variant and divergent from those previously described from human patients in Argentina. Furthermore, unlike in human cases following treatment with ivermectin, the dog was negative after moxidectin treatment according to polymerase chain reaction of the sampled faeces. Conclusions: This case report shows the importance of further investigation into potential transmission events and prevalences of S. stercoralis in dogs and humans in South America. The results reported here should also encourage future work that examines different scenarios of infection with S. stercoralis in dogs and humans with the aim of integrating clinical management, diagnosis, treatment and follow-up strategies in the quest for new approaches for the treatment of this disease in animals and humans. The findings support the adoption of a One Health approach, which recognizes the interconnectedness between animal and human health, in addressing parasitic infections such as strongyloidiasis

Molecular Identification of Trypanosma cruzi discrete Typing Units in end-Stage Chronic Chagas Heart Disease and Reactivation after Heart Transplantation

One hundred years after the discovery of Chagas disease, it remains a major neglected tropical disease. Chronic Chagas heart disease is the most severe manifestation. Heart trasplantation is the proper treatment for end-stage heart failure. T. cruzi strains cluster into 6 discrete typing units assosiated with different geographical distribution, transmission cycles and varying disease symptoms.In the southern cone of South America, T. cruzi II, V and VI popuations appear to be assosiated with Chagas disease and T. cruzi I with sylvatic cycles.Fil: Burgos, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Invest. Biotec. (subsede San Martin) | Universidad Nacional de San Martin. Instituto de Investigaciones Biotecnológicas. Instituto de Invest. Biotec. (subsede San Martin); Argentina. Laboratorio Biología Molecular de Enfermedad de Chagas; ArgentinaFil: Diez, Mirta. Universidad Favaloro; ArgentinaFil: Vigliano, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; ArgentinaFil: Bisio, Margarita María Catalina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Risso, Marikena Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Duffi, Tomas. Laboratorio Biología Molecular de Enfermedad de Chagas; ArgentinaFil: Cura, Carolina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Grupo Vinculado al INGEBI- Laboratorio de Biocatálisis y Biotransformaciones - LBB - UNQUI; ArgentinaFil: Brusés, Bettina Laura. Universidad Nacional del Nordeste. Instituto de Medicina Regional; ArgentinaFil: Favaloro, Liliana Ethel. Universidad Favaloro; ArgentinaFil: Leguizamon, María Susana. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Lucero, Raúl Horacio. Universidad Nacional del Nordeste. Instituto de Medicina Regional; ArgentinaFil: Laguens, Rubén. Universidad Favaloro; ArgentinaFil: Levin, Mariano Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Grupo Vinculado al INGEBI- Laboratorio de Biocatálisis y Biotransformaciones - LBB - UNQUI; ArgentinaFil: Favaloro, Roberto René. Universidad Favaloro; ArgentinaFil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Laboratorio Biología Molecular de Enfermedad de Chagas; Argentin

First identification of Strongyloides stercoralis infection in a pet dog in Argentina, using integrated diagnostic approaches

2023 Acuerdos transformativos CRUEBackground: Strongyloides stercoralis is a soil-transmitted intestinal nematode with a complex life cycle that primarily affects humans, non-human primates, dogs, and occasionally cats. This study presents, to the best of our knowledge, the first case of S. stercoralis infection and its genotyping in a domestic dog from Argentina. Methods: The patient was a female wired-haired Teckel dog exhibiting recurrent coughing. Coproparasitological analysis using the Baermann technique revealed the presence of rhabditiform larvae morphologically compatible with S. stercoralis. To confirm this finding, molecular diagnosis (18S ribosomal RNA) and analysis of the cox1 gene were performed. Results: We identified a haplotype (HP20) that has previously only been related to S. stercoralis infection in dogs, but was found in the present study to be highly related to the haplotype (HP16) of a zoonotic variant and divergent from those previously described from human patients in Argentina. Furthermore, unlike in human cases following treatment with ivermectin, the dog was negative after moxidectin treatment according to polymerase chain reaction of the sampled faeces. Conclusions: This case report shows the importance of further investigation into potential transmission events and prevalences of S. stercoralis in dogs and humans in South America. The results reported here should also encourage future work that examines different scenarios of infection with S. stercoralis in dogs and humans with the aim of integrating clinical management, diagnosis, treatment and follow-up strategies in the quest for new approaches for the treatment of this disease in animals and humans. The findings support the adoption of a One Health approach, which recognizes the interconnectedness between animal and human health, in addressing parasitic infections such as strongyloidiasis.Depto. de Sanidad AnimalFac. de VeterinariaTRUEpubAPC financiada por la UC

Strongyloidiasis Outside Endemic Areas: Long-term Parasitological and Clinical Follow-up after Ivermectin Treatment

Background Strongyloides stercoralis affects 30-100 million people worldwide. The first-line therapy is ivermectin. Cure is defined as the absence of larvae by parasitological methods 1 year after treatment. To date, no longitudinal parasitological studies for longer periods of time have been conducted to confirm its cure. Here, we evaluated treatment response in long-term follow-up patients with chronic infection using parasitological and molecular methods for larvae or DNA detection. Methods A prospective, descriptive, observational study was conducted between January 2009 and September 2015 in Buenos Aires, Argentina. Twenty-one patients with S. stercoralis diagnosis were evaluated 30, 60, and 90 days as well as 1, 2, 3, and/or 4 years after treatment by conventional methods (fresh stool, Ritchie method, agar plate culture), S. stercoralis-specific polymerase chain reaction (PCR) in stool DNA, and eosinophil values. Results During follow-up, larvae were detected by conventional methods in 14 of 21 patients. This parasitological reactivation was observed starting 30 days posttreatment (dpt) and then at different times since 90 dpt. Eosinophil values decreased (P =.001) 30 days after treatment, but their levels were neither associated with nor predicted these reactivations. However, S. stercoralis DNA was detected by PCR in all patients, both in their first and subsequent stool samples, thus reflecting the poor efficacy of ivermectin at eradicating parasite from host tissues. Asymptomatic eosinophilia was the most frequent clinical form among chronically infected patients. Conclusions These results suggest that the parasitological cure is unlikely. Strongyloidiasis must be considered a chronic infection and ivermectin administration schedules should be reevaluated.Fil: Repetto, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Ruybal, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Batalla, Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: López, Carlota. Hospital Durand; ArgentinaFil: Fridman, Vanesa. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Sierra, Mariela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Radisic, Marcelo. Instituto de Nefrología de Buenos Aires; ArgentinaFil: Bravo, Pablo M.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Risso, Marikena Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: González, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Hidden Structural Codes in Protein Intrinsic Disorder

Intrinsic disorder is a major structural category in biology, accounting for more than 30% of coding regions across the domains of life, yet consists of conformational ensembles in equilibrium, a major challenge in protein chemistry. Anciently evolved papillomavirus genomes constitute an unparalleled case for sequence to structure-function correlation in cases in which there are no folded structures. E7, the major transforming oncoprotein of human papillomaviruses, is a paradigmatic example among the intrinsically disordered proteins. Analysis of a large number of sequences of the same viral protein allowed for the identification of a handful of residues with absolute conservation, scattered along the sequence of its N-terminal intrinsically disordered domain, which intriguingly are mostly leucine residues. Mutation of these led to a pronounced increase in both α-helix and β-sheet structural content, reflected by drastic effects on equilibrium propensities and oligomerization kinetics, and uncovers the existence of local structural elements that oppose canonical folding. These folding relays suggest the existence of yet undefined hidden structural codes behind intrinsic disorder in this model protein. Thus, evolution pinpoints conformational hot spots that could have not been identified by direct experimental methods for analyzing or perturbing the equilibrium of an intrinsically disordered protein ensembleFil: Borkosky, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Camporeale, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Chemes, Lucia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Risso, Marikena Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Noval, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. University of New York; Estados UnidosFil: Sánchez Miguel, Ignacio Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Alonso, Leonardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Reply to Buonfrate and Bisoffi

To the Editor ? We thank Drs Buonfrate and Bisof for reading our article. Our small long-term observational follow-up study included 21 ivermectin-treated patients; 14 of them presented with reactivation by larvae observation [1]. A few years ago, our group reported that 1 of 10 patients with strongyloidiasis showed a persistent increase in eosinophil counts beginning 4 months afer ivermectin treatment, reaching values of eosinophilia afer the 10th month of follow-up [2]. According to this observation, 3?4 consecutive stool samples were exhaustively examined by agar plate culture (APC). In the third test, at the 10th month, Strongyloides stercoralis larvae were detected [2]. Subsequently, a polymerase chain reaction (PCR) protocol was standardized to facilitate diagnosis in patients with chronic infection and low parasitic load, 2 of the main features of patients who attend the hospital seeking medical advice for immunocompromise or eosinophilia. Tis technique showed a sensitivity of 100% owing to the DNA extraction method (a key diagnosis step) that combines mechanical and chemical lysis. Te standardized extraction method recovered superior quality DNA compared with the sole use of the commercial kit [3]. Te high performance of DNA isolation together with amplifcation reaction mix optimization made PCR a key tool for the early diagnosis of this parasitosis [4]. However, during the follow-up presented here, our results of persistent positive PCR in every stool sample following ivermectin treatment were surprising. Aferward, parasitological reactivation was confrmed in 14 of 21 patients, suggesting that the current ivermectin schedule of 200 μg/kg/day for 2 days and repeated 2 weeks apart [5] might not be effective for parasite eradication. It is noteworthy that in 9 of 14 patients with parasitological reactivation, the number of larvae observed by APC was low (1?6 larvae/3 g stool sample in APC), being that the patients were asymptomatic. We agree that the number of patients in our study is, although statistically valid, low. However, reaching our goal of parasitological and clinical follow-up of patients in the long term was extremely difcult. Te complex cycle of S. stercoralis and the particular immune response against the autoinfective flariform larvae favor the establishment of chronic infection. In addition, larvae can remain in diapause in currently unknown niches from where, following different stimuli, they can reach the small intestine and differentiate into adult parasites. In this context, we do not underestimate the usefulness of ivermectin at decreasing the initial parasitic load. Still, our results advocate that additional doses of ivermectin or a prolonged treatment schedule should be attempted to eradicate parasitic females and decrease the L3a circulating larvae. Strongyloidiasis is a parasitic disease with chronic evolution and fluctuating parasitic load over time. Based on our results, we strongly recommend for studies on ivermectin activity against strongyloidiasis such as the randomized controlled trial (Strong Treat Trial), which enrolled a large cohort of patients, a long-term follow-up (far beyond 12 months), and quantitative molecular techniques to reach a better understanding on the evolution of this infection. In line with this, we await the trial results, which will surely enrich our knowledge on this parasitosis.Fil: Repetto, Silvia A. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Ruybal, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Batalla, Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: López, Carlota. Hospital General de Agudos Carlos G. Durand; ArgentinaFil: Fridman, Vanesa. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Sierra, Mariela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Radisic, Marcelo. Instituto de Nefrología de Buenos Aires; ArgentinaFil: Bravo, Pablo M.. Instituto de Nefrología de Buenos Aires; ArgentinaFil: Risso, Marikena Guadalupe. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: González, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Alba Soto, Catalina Dirney. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein

Infection with oncogenic human papillomavirus induces deregulation of cellular redox homeostasis. Virus replication and papillomavirus-induced cell transformation require persistent expression of viral oncoproteins E7 and E6 that must retain their functionality in a persistent oxidative environment. Here, we dissected the molecular mechanisms by which E7 oncoprotein can sense and manage the potentially harmful oxidative environment of the papillomavirus-infected cell. The carboxy terminal domain of E7 protein from most of the 79 papillomavirus viral types of alpha genus, which encloses all the tumorigenic viral types, is a cysteine rich domain that contains two classes of cysteines: strictly conserved low reactive Zn+2 binding and degenerate reactive cysteine residues that can sense reactive oxygen species (ROS). Based on experimental data obtained from E7 proteins from the prototypical viral types 16, 18 and 11, we identified a couple of low pKa nucleophilic cysteines that can form a disulfide bridge upon the exposure to ROS and regulate the cytoplasm to nucleus transport. From sequence analysis and phylogenetic reconstruction of redox sensing states we propose that reactive cysteine acquisition through evolution leads to three separate E7s protein families that differ in the ROS sensing mechanism: non ROS-sensitive E7s; ROS-sensitive E7s using only a single or multiple reactive cysteine sensing mechanisms and ROS-sensitive E7s using a reactive-resolutive cysteine couple sensing mechanismFil: Camporeale, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Lorenzo, Juan R.. Universite Libre de Bruxelles; BélgicaFil: Thomas, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Salvatierra, Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Borkosky, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Risso, Marikena Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Sánchez Miguel, Ignacio Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Alonso, Leonardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin