Evolution of Animal South American RVA Told by the NSP4 Gene E12 Genotype

Rotavirus A (RVA) possesses a genome of 11 double-stranded (ds) RNA segments, and each segment encodes one protein, with the exception of segment 11. NSP4 is a non-structural multifunctional protein encoded by segment 10 that defines the E-genotype. From the 31 E-genotypes described, genotype E12 has been described in Argentina, Uruguay, Paraguay, and Brazil in RVA strains infecting different animal species and humans. In this work, we studied the evolutionary relationships of RVA strains carrying the E12 genotype in South America using phylogenetic and phylodynamic approaches. We found that the E12 genotype has a South American origin, with a guanaco (Lama guanicoe) strain as natural host. Interestingly, all the other reported RVA strains carrying the E12 genotype in equine, bovine, caprine, and human strains are related to RVA strains of camelid origin. The evolutionary path and genetic footprint of the E12 genotype were reconstructed starting with the introduction of non-native livestock species into the American continent with the Spanish conquest in the 16th century. The imported animal species were in close contact with South American camelids, and the offspring were exposed to the native RVA strains brought from Europe and the new RVA circulating in guanacos, resulting in the emergence of new RVA strains in the current lineages’ strongly species-specific adaption. In conclusion, we proposed the NSP4 E12 genotype as a genetic geographic marker in the RVA strains circulating in different animal species in South America.EEA Cerro AzulFil: Miño, Samuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Cerro Azul; Argentina.Fil: Badaracco, Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Montecarlo; ArgentinaFil: Louge Uriarte, Enrique Leopoldo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Ciarlet, Max. Icosavax. Clinical Development; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentin

Molecular characterization of equine rotaviruses circulating in Argentinean foals during a 17-year surveillance period (1992-2008)

P[12]G3 and P[12]G14 equine rotaviruses (ERVs) are epidemiologically important in horses. In Argentina, the prevalent ERV strains have been historically P[12]G3. The aim of this study was the detection and characterization of ERV strains circulating in foals in Argentina during a 17-year study (1992-2008). Additionally, the gene sequences of VP7, VP4 and NSP4 encoding genes of representative Argentinean ERV strains were determined and phylogenetic analyses were performed to elucidate the evolutionary relationships of the ERV strains in Argentina. ERVs were detected in 165 (21%) out of 771 diarrheic stool samples, which corresponded to 45 (39%) of 116 outbreaks from the surveyed thoroughbred horse farms. From the positive cases, 51% (n= 23) were G3, 33% (n= 15) were G14, 4% (n= 2) represented a G3. +. G14 mixed infection and 11% (n= 5) of the cases could not be characterized. G3 ERV was detected during the entire period, while G14 ERV was first detected in 2000 and increased its incidence specially in 2006 and 2007. All the analyzed strains belonged to the VP4 P[12] genotype, except for one G3 case which belonged to the P[3] genotype, constituting the first report of a P[3]G3 ERV strain. Phylogenetic analysis of VP7 protein revealed that the G3 Argentinean ERV strains clustered with ERVs from Ireland, while the G14 Argentinean ERV strains formed a distinct cluster within the G14 genotype. The VP4 of the P[12] ERV strains clustered with P[12] strains from Ireland and France. The NSP4 of the Argentinean ERV strains clustered with the NSP4 genotype E12, along with those of guanaco and bovine strains from Argentina, suggesting the a close evolutionary relationship among these Argentinean strains. The results of this study showed changes in the incidence of G3 and G14 during the studied period. The increase in the frequency of G14 ERV, not included in the vaccine, in the second half of the period, may have implications for vaccine design.Fil: Garaicoechea, Lorena Laura. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miño, Samuel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Ciarlet, Max. No especifíca;Fil: Fernández, Fernando. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Barrandeguy, María. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Efficacy of the Pentavalent Rotavirus Vaccine, RotaTeq (RV5), Between Doses of a 3-Dose Series and With Less Than 3 Doses (Incomplete Regimen)

Post-hoc analyses of the Rotavirus Efficacy and Safety Trial (RES T) were conducted to determine whether the pentavalent rotavirus vaccine (RV5) confers early protection against rotavirus gastroenteritis (RVGE) before completion of the 3-dose regimen. To evaluate the efficacy of RV5 between doses in reducing the rates of RVGE-related hospitalizations and emergency department (ED) visits in infants who ultimately received all 3 doses of RV5/placebo, events occurring from 2 weeks after the first and second doses to receipt of the subsequent dose (Analysis A) and events occurring from 2 weeks after the first and second doses to 2 weeks after the subsequent dose (Analysis B) were analyzed. In Analysis A, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype between doses 1 and 2 by 100% [95% confidence interval (CI): 72-100%] or 82% (95% CI: 39-97%), respectively, and between doses 2 and 3, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype by 91% (95% CI: 63-99%) or 84% (95% CI: 54-96%), respectively. Similar rate reductions were observed in Analysis B. These data suggest that RV5 provides a high level of protection between doses against hospitalizations and ED visits for RVGE starting as early as 14 days after the first dose

Finite Element Convergence for the Joule Heating Problem with Mixed Boundary Conditions

We prove strong convergence of conforming finite element approximations to the stationary Joule heating problem with mixed boundary conditions on Lipschitz domains in three spatial dimensions. We show optimal global regularity estimates on creased domains and prove a priori and a posteriori bounds for shape regular meshes.Comment: Keywords: Joule heating problem, thermistors, a posteriori error analysis, a priori error analysis, finite element metho

Complete molecular genome analyses of equine rotavirus a strains from different continents reveal several novel genotypes and a largely conserved genotype constellation

In this study, the complete genome sequences of seven equine group A rotavirus (RVA) strains (RVA/Horse-tc/GBR/L338/1991/G13P[18], RVA/Horse-wt/IRL/03V04954/2003/G3P[12] and RVA/Horse-wt/IRL/04V2024/2004/G14P[12] from Europe; RVA/Horse-wt/ARG/E30/1993/ G3P[12], RVA/Horse-wt/ARG/E403/2006/G14P[12] and RVA/Horse-wt/ARG/E4040/2008/ G14P[12] from Argentina; and RVA/Horse-wt/ZAF/EqRV-SA1/2006/G14P[12] from South Africa) were determined. Multiple novel genotypes were identified and genotype numbers were assigned by the Rotavirus Classification Working Group: R9 (VP1), C9 (VP2), N9 (NSP2), T12 (NSP3), E14 (NSP4), and H7 and H11 (NSP5). The genotype constellation of L338 was unique: G13-P[18]-I6- R9-C9-M6-A6-N9-T12-E14-H11. The six remaining equine RVA strains showed a largely conserved genotype constellation: G3/G14-P[12]-I2/I6-R2-C2-M3-A10-N2-T3-E2/E12-H7, which is highly divergent from other known non-equine RVA genotype constellations. Phylogenetic analyses revealed that the sequences of these equine RVA strains are related distantly to nonequine RVA strains, and that at least three lineages exist within equine RVA strains. A small number of reassortment events were observed. Interestingly, the three RVA strains from Argentina possessed the E12 genotype, whereas the three RVA strains from Ireland and South Africa possessed the E2 genotype. The unusual E12 genotype has until now only been described in Argentina among RVA strains collected from guanaco, cattle and horses, suggesting geographical isolation of this NSP4 genotype. This conserved genetic configuration of equine RVA strains could be useful for future vaccine development or improvement of currently used equine RVA vaccines.Fil: Matthijnssens, Jelle. Katholikie Universiteit Leuven; BélgicaFil: Miño, Orlando Samuel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Papp, Hajnalka. Hungarian Academy of Sciences; HungríaFil: Potgieter, Christiaan. Ondersterpoort Veterinary Institute; SudáfricaFil: Novo, Luis. Katholikie Universiteit Leuven; BélgicaFil: Heylen, Elisabeth. Katholikie Universiteit Leuven; BélgicaFil: Zeller, Mark. Katholikie Universiteit Leuven; BélgicaFil: Garaicoechea, Lorena Laura. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Badaracco, Alejandra. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lengyel, György. Dr György Radó Military Medical Centre; HungríaFil: Kisfali, Péter. University Of Pécs; HungríaFil: Cullinane, Ann. Irish Equine Centre; IrlandaFil: Collins, P. J.. Cork Ins Of Technology; IrlandaFil: Ciarlet, Max. Novartis Vaccines and Diagnostics; Estados UnidosFil: O'Shea, Helen. Cork Ins Of Technology; IrlandaFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bányai, Krisztián. Hungarian Academy of Sciences; HungríaFil: Barrandeguy, María Edith. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Van Ranst, Marc. Katholikie Universiteit Leuven; Bélgic

Efficacy of the pentavalent rotavirus vaccine, RotaTeq®, in Finnish infants up to 3 years of age: the Finnish Extension Study

Rotavirus Efficacy and Safety Trial (REST) enrolled nearly 70,000 infants, of whom more than 23,000 were from Finland. REST determined the efficacy of the pentavalent rotavirus vaccine (RV5) against rotavirus-related hospitalisations and emergency department (ED) visits in the first year after vaccination. Finnish infants initially in REST transitioned into the Finnish Extension Study (FES), where they were followed for rotavirus-related hospitalisations and ED visits through their second year of life and beyond. FES identified 150 (31%) additional rotavirus gastroenteritis (RVGE) cases beyond those identified in REST in the Finnish participants. Overall, RV5 reduced RVGE hospitalisations and ED visits, regardless of the rotavirus serotype, by 93.8% (95% confidence interval [CI]: 90.8–95.9%) for up to 3.1 years following the last vaccine dose. Vaccine efficacy against combined hospitalisations and ED visits between ages 4 months to 11 months, 12 months to 23 months, and 24 months to 35 months was 93.9% (95% CI: 89.1–96.9%), 94.4% (95% CI: 90.2–97.0%), and 85.9% (95% CI: 51.6–97.2%), respectively. The reduction of hospitalisations and ED visits due to any acute gastroenteritis, rotavirus or not, was 62.4% (95% CI: 57.6–66.6%) over the entire follow-up period. The results from FES confirm that RV5 induces high and sustained protection against rotavirus-related hospitalisations and ED visits, and has a very substantial impact on all gastroenteritis-related hospitalisations and ED visits into the third year of life in Finnish children

Relationships among porcine and human P[6] rotaviruses: Evidence that the different human P[6] lineages have originated from multiple interspecies transmission events

AbstractPorcine rotavirus strains (PoRVs) bearing human-like VP4 P[6] gene alleles were identified. Genetic characterization with either PCR genotyping or sequence analysis allowed to determine the VP7 specificity of the PoRVs as G3, G4, G5 and G9, and the VP6 as genogroup I, that is predictive of a subgroup I specificity. Sequence analysis of the VP8* trypsin-cleavage product of VP4 allowed PoRVs to be characterized further into genetic lineages within the P[6] genotype. Unexpectedly, the strains displayed significantly higher similarity (up to 94.6% and 92.5% at aa and nt level, respectively) to human M37-like P[6] strains (lineage I), serologically classifiable as P2A, or to the atypical Hungarian P[6] human strains (HRVs), designated as lineage V (up to 97.0% aa and 96.1% nt), than to the porcine P[6] strain Gottfried, lineage II (<85.1% aa and 82.2 nt), which is serologically classified as P2B. Interestingly, no P[6] PoRV resembling the original prototype porcine strain, Gottfried, was detected, while Japanase P[6] PoRV clustered with the atypical Japanase G1 human strain AU19. By analysis of the 10th and 11th genome segments, all the strains revealed a NSP4B genogroup (Wa-like) and a NSP5/6 gene of porcine origin. These findings strongly suggest interspecies transmission of rotavirus strains and/or genes, and may indicate the occurrence of at least 3 separate rotavirus transmission events between pigs and humans, providing convincing evidence that evolution of human rotaviruses is tightly intermingled with the evolution of animal rotaviruses

Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG)

In April 2008, a nucleotide-sequence-based, complete genome classification system was developed for group A rotaviruses (RVs). This system assigns a specific genotype to each of the 11 genome segments of a particular RV strain according to established nucleotide percent cutoff values. Using this approach, the genome of individual RV strains are given the complete descriptor of Gx-P[x]-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx. The Rotavirus Classification Working Group (RCWG) was formed by scientists in the field to maintain, evaluate and develop the RV genotype classification system, in particular to aid in the designation of new genotypes. Since its conception, the group has ratified 51 new genotypes: as of April 2011, new genotypes for VP7 (G20-G27), VP4 (P[28]-P[35]), VP6 (I12-I16), VP1 (R5-R9), VP2 (C6-C9), VP3 (M7-M8), NSP1 (A15-A16), NSP2 (N6-N9), NSP3 (T8-T12), NSP4 (E12-E14) and NSP5/6 (H7-H11) have been defined for RV strains recovered from humans, cows, pigs, horses, mice, South American camelids (guanaco), chickens, turkeys, pheasants, bats and a sugar glider. With increasing numbers of complete RV genome sequences becoming available, a standardized RV strain nomenclature system is needed, and the RCWG proposes that individual RV strains are named as follows: RV group/species of origin/country of identification/common name/year of identification/G- and P-type. In collaboration with the National Center for Biotechnology Information (NCBI), the RCWG is also working on developing a RV-specific resource for the deposition of nucleotide sequences. This resource will provide useful information regarding RV strains, including, but not limited to, the individual gene genotypes and epidemiological and clinical information. Together, the proposed nomenclature system and the NCBI RV resource will offer highly useful tools for investigators to search for, retrieve, and analyze the ever-growing volume of RV genomic data.Fil: Matthijnssens, Jelle. Katholikie Universiteit Leuven; BélgicaFil: Ciarlet, Max. Novartis Vaccines & Diagnostics; Estados UnidosFil: McDonald, Sarah M.. National Institute Of Allegry & Infectious Diseases (niaid) ; National Institutes Of Health;Fil: Attoui, Houssam. Animal Health Trust.; Reino UnidoFil: Bányai, Krisztián. Hungarian Academy of Sciences; HungríaFil: Brister, J. Rodney. National Library Of Medicine; Estados UnidosFil: Buesa, Javier. Universidad de Valencia; EspañaFil: Esona, Mathew D.. Centers for Disease Control and Prevention; Estados UnidosFil: Estes, Mary K.. Baylor College of Medicine; Estados UnidosFil: Gentsch, Jon R.. Centers for Disease Control and Prevention; Estados UnidosFil: Iturriza Gómara, Miren. Health Protection Agency; Reino UnidoFil: Johne, Reimar. Federal Institute for Risk Assessment; AlemaniaFil: Kirkwood, Carl D.. Royal Children's Hospital; AustraliaFil: Martella, Vito. Università degli Studi di Bari; ItaliaFil: Mertens, Peter P. C.. Animal Health Trust.; Reino UnidoFil: Nakagomi, Osamu. Nagasaki University; JapónFil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Rahman, Mustafizur. International Centre For Diarrhoeal Disease Research; BangladeshFil: Ruggeri, Franco M.. Istituto Superiore Di Sanita; ItaliaFil: Saif, Linda J.. Ohio State University; Estados UnidosFil: Santos, Norma. Universidade Federal do Rio de Janeiro; BrasilFil: Steyer, Andrej. University of Ljubljan; EsloveniaFil: Taniguchi, Koki. Fujita Health University School of Medicine; JapónFil: Patton, John T.. National Institute Of Allegry & Infectious Diseases (niaid) ; National Institutes Of Health;Fil: Desselberger, Ulrich. University of Cambridge; Estados UnidosFil: van Ranst, Marc. Katholikie Universiteit Leuven; Bélgic

Serotype-specific immune response against porcina rotaviruses

Se evaluó la respuesta inmunitaria serotipo específica contra rotavirus porcinos, en sueros de lechones y sueros hiperinmunes producidos en conejo, mediante un ELISA de competencia. El uso de una batería de 6 anticuerpos monoclonales (AcM) producidos contra la proteína VP7 de los serotipos G3, G5 o G11 y un AcM contra el segmento VP8* de la proteína VP4 del serotipo P9, permitió la identificación de tres grupos de reactividad. El primer grupo, representado por los AcM dirigidos a los serotipos G3 y G5, definido por el reconocimiento recíproco de los AcM 1C10 y 7D2 y, otro no recíproco por el AcM lC3. El segundo grupo de reactividad formado por los AcM de serotipo porcino Gil, definido por el reconocimiento recíproco de los AcM 6E10 y 8D10 y el no recíproco del AcM 5E6. El AcM 4B2, dirigido contra VP8*, representó el tercer grupo de reactividad. La respuesta inmunitaria en sueros hiperinmunes fue serotipo específica y apoyó la presencia de un epitope común sobre las VP7 G3 y G5 porcinas y de un dominio exclusivo sobre el serotipo Gl1 porcino. En lechones de 1 a 8 semanas de edad, se encontraron niveles considerables de anticuerpos que compitieron con el panel de AcM, sugiriendo que pudieran estar representados en el repertorio de anticuerpos que se producen por infección natural.114 - 118BimestralThe serotype-specific immune response against porcine rotaviruses was evaluated in piglets and hyperimmune sera raised in rabbits by a competition ELISA. Using 6 monoclonal antibodies (Mabs) directed against G3, G5 and G11 VP7 and one Mab directed against P9 VP8* cleavage product of VP4, three distinct reactivity group were identified: reactivity group represented porcine rotavirus serotypes G3 and G5, defined by the reciprocal recognition of 1C10 and 7D2 and by the nonreciprocal recognition of the Mab 1C3; represented porcine rotavirus G11, defined by the reciprocal recognition of Mab 6E10 and 8D10, and by the non-reciprocal recognition of Mab 5E6 and the one represented by Mab 4B2, directed against VP8*. In rabbit hyperimmune sera the immune response was serotype-specific and supported the presence of a commonepitope on both G3 and G5 VP7 types, as well as an exclusive domain for serotype G11. In 1- to 8-weeks old piglets, considerable levels of antibodies competed out all Mabs tested suggesting that the Mabs are represented in the antibody repertoire produced after natural infection of porcine rotavirus