ABSTRACT The immune response elicited by the rotavirus nonstructural protein NSP4 and its potential role in protection against rotavirus disease are not well understood. We investigated the serological response to NSP4 and its correlation with disease protection in sera from 110 children suffering acute diarrhea, associated or not with rotavirus, and from 26 children who were recipients of the rhesus rotavirus tetravalent (RRV-TV) vaccine. We used, as antigens in an enzyme-linked immunosorbent assay (ELISA), affinity-purified recombinant NSP4 (residues 85 to 175) from strains SA11, Wa, and RRV (genotypes A, B, and C, respectively) fused to glutathione S -transferase. Seroconversion to NSP4 was observed in 54% (42/78) of the children who suffered from natural rotavirus infection and in 8% (2/26) of the RRV-TV vaccine recipients. Our findings indicate that NSP4 evokes significantly ( P < 0.05) higher seroconversion rates after natural infection than after RRV-TV vaccination. The serum antibody levels to NSP4 were modest (titers of ≤200) in most of the infected and vaccinated children. A heterotypic NSP4 response was detected in 48% of the naturally rotavirus-infected children with a detectable response to NSP4. Following natural infection or RRV-TV vaccination, NSP4 was significantly less immunogenic than the VP6 protein when these responses were independently measured by ELISA. A significant ( P < 0.05) proportion of children who did not develop diarrhea associated with rotavirus had antibodies to NSP4 in acute-phase serum, suggesting that serum antibodies against NSP4 might correlate with protection from rotavirus diarrhea. In addition, previous exposures to rotavirus did not affect the NSP4 seroconversion rate.
The aim of our study was to determine whether the severity of rotavirus gastroenteritis may be related to the different characteristics of infecting viral strains. The severity of clinical symptoms in 401 children with acute rotavirus gastroenteritis was assessed using a scoring system for frequency and duration of vomiting, diarrhea, and fever, as well as the patients' requirements for intravenous rehydration. Rotavirus strains were characterized by determining the electropherotype of their double-stranded RNA, the G type and subgroup by a panel of monoclonal antibodies, and the P type by reverse transcription-polymerase chain reaction. Strains with a short electropherotype, G2P[4] type, and subgroup I were associated with more-severe gastroenteritis and affected children older than those infected with strains with a long electropherotype, G1P[8] or G4P[8] type, and subgroup II. Minor differences in clinical symptoms were also detected in children infected with different long electropherotypes and with G1P[8] and G4P[8] specificities.
El nuevo coronavirus causante de la COVID-19 es llamado SARS-CoV-2 y pertenece al subgenero Sarbecovirus, como suantecesor el SARS-CoV. Los murcielagos parecen ser los hospederos de los virus ancestrales que los originaron, a traves de la recombinacioncon el virus de un animal intermediario, que podria ser el pangolin. El SARS-CoV-2 interactua con su receptor ACE2 (enzima convertidorade angiotensina 2) y entra a la celula por la via endocitica, a traves de un endosoma temprano o tardio. El ARN viral funge como ARNmensajero para la traduccion del primer marco de lectura y el resto de los ARN mensajeros son producidos por transcripcion discontinua.Esta peculiaridad le confiere a esta familia viral una alta frecuencia de recombinacion, la cual esta asociada con la alta frecuencia de saltode especie. Los virus pertenecientes al orden Nidovirales, al cual pertenece el SARS-CoV-2, son los unicos virus ARN conocidos cuyapolimerasa tiene actividad correctora, por lo que su tasa de mutacion se ve reducida. Sin embargo, estos genomas parecen ser susceptiblesa la desaminacion por enzimas celulares. Todos estos mecanismos de generacion de diversidad se traducen en la existencia de linajes,entre los cuales, los que poseen la mutacion D614G en la espiga, podrian ser mas transmisibles. Sin embargo, no se conocen hasta la fechamutaciones asociadas a una mayor gravedad. Asi como existen diferentes variantes virales, la manifestacion clinica de la enfermedad estambien muy variable. Se empiezan a conocer algunos factores geneticos, fisiologicos y metabolicos que podrian estar determinando formasclinicas mas graves, a menudo asociadas a la inmunopatologia de esta enfermedad.
Rotavirus (RV) is the most common cause of severe childhood diarrhea worldwide. Despite Venezuela was among the first developing countries to introduce RV vaccines into their national immunization schedules, RV is still contributing to the burden of diarrhea. Concerns exist about the selective pressure that RV vaccines could exert on the predominant types and/or emergence of new strains. To assess the impact of RV vaccines on the genotype distribution 1 year after the vaccination was implemented, a total of 912 fecal specimens, collected from children with acute gastroenteritis in Caracas from February 2007 to April 2008, were screened, of which 169 (18.5%) were confirmed to be RV positive by PAGE. Rotavirus-associated diarrhea occurred all year-round, although prevailed during the coolest and driest months among unvaccinated children under 24 months old. Of 165 RV strains genotyped for G (VP7) and P (VP4) by seminested multiplex RT-PCR, 77 (46.7%) were G2P[4] and 63 (38.2%) G1P[8]. G9P[8], G3P[8] and G2P[6] were found in a lower proportion (7.3%). Remarkable was also the detection of <5% of uncommon combinations (G8P[14], G8P[4], G1P[4] and G4P[4]) and 3.6% of mixed infections. A changing pattern of G/P-type distribution was observed during the season studied, with complete predominance of G2P[4] from February to June 2007 followed by its gradual decline and the reemergence of G1P[8], predominant since January 2008. Phylogenetic analysis of VP7 and VP4 genes revealed a high similarity among G2P[4] and global strains belonging to G2-II and P[4]-V lineages. The amino acid substitution 96D → N, related with reemergence of the G2 genotype elsewhere, was observed. The G1P[8] strains from Caracas were grouped into the lineages G1-I and P[8]-III, along with geographically remote G1P[8] rotaviruses, but they were rather distant from Rotarix® vaccine and pre-vaccine strains. Unique amino acid substitutions observed on neutralization domains of the VP7 sequence from Venezuelan post-vaccine G1P[8] could have conditioned their re-emergence and a more efficient dissemination into susceptible population. The results suggest that natural fluctuations of genotypes in combination with forces driving the genetic evolution could determine the spread of novel strains, whose long-term effect on the efficacy of available vaccines should be determined.
Introducción: El agente etiológico responsable de COVID-19, SARSCoV-2, es un virus ARN perteneciente a la familia Coronaviridae. Durante la replicación, los componentes virales interactúan con la maquinaria celular induciendo alteraciones en la fisiología celular, lo que contribuye a la patogénesis del virus. Método: Revisión bibliográfica en NCBI/Pubmed sobre estrés celular y SARS-CoV-2 Hallazgos de interpretación: Como respuesta a la infección, en la célula hospedadora se activan vías de señalización, cuyo principal objetivo es recuperar la homeostasis y de no lograrlo, inducir a la activación de la muerte celular. Entre las vías de señalización mejor caracterizadas, destacan las rutas de estrés celular como el estrés oxidativo, la UPR (Respuesta a proteínas no plegadas), y la autofagia, las cuales son evolutivamente bien conservadas y además están interconectadas entre sí. Hay fuerte evidencia teórica y experimental de diversas interacciones de algunos componentes de estas rutas con distintas proteínas virales de los coronavirus, y ya se han adelantado algunos estudios con SARS-CoV-2. En esta revisión, resaltamos algunas de las rutas celulares-virus que se han caracterizado hasta el momento.
Reflexiones finales: Aún queda mucho por entender de estas rutas y su relación con las infecciones virales; esto pudiera constituir un importante blanco para la investigación y desarrollo de terapias antivirales.
Background: Human rotavirus (RV) is considered the main viral cause of acute gastroenteritis in children in both developed and developing countries. The recent implementation of a vaccination program promises to effectively reduce the disease burden and health care costs of rotavirus-specific diarrhea. Surveillance is needed to assess the impact of immunization on the rotavirus diarrhea incidence and variability of the circulating strains. In the last decades, RV molecular genotyping has provided valuable information about the diversity of rotavirus outer capside proteins (VP7/G and VP4/P) of strains circulating throughout the world. Previous studies have demonstrated a broad diversity in rotavirus strains circulating in Venezuela, with predominance of G1, G3 or G4 in combination with P[8] type. The purpose of the present study was to monitor the prevalence of the G/PNSP4 genotypes of rotaviruses circulating in Caracas between February 2007 and April 2008 and detect any uncommon or novel types by means of molecular characterization. Methods: A total of 164 rotavirus-positive stools from diarrheic pediatric patients aged between 2 months and 5 years collected in Caracas, were tested by multiplex seminested RT-PCR and/or sequencing of the VP4, VP7 and NSP4 rotavirus gene. Results: The analysis revealed 5 common G/P-NSP4 combinations, being G2P[4]/NSP4A and G1P[8]/NSP4B the most prevalent (43% and 38%, respectively), while G3-, G4- or G9- P[8]/NSP4B were more sporadically found. Although present throughout the period studied, G2P[4]-NSP4A rotavirus was the most widely circulating type until November 2007, from then being prevalent G1P[8]-NSP4B strains. Four isolates showed an unusual genotype G8P[14], until now only described in Latino America among animal rotaviruses, 3 of the isolates being associated with NSP4C and one with NSP4A genotype. Conclusion: This study highlights the wide genetic diversity among rotaviruses isolated in Caracas, the temporal variation of the predominant types and the occurrence of a unusual type, G8P[14], described for the first time among humans in our region, probably derived from interspecies transmission. Therefore, it is crucial to continuously monitor circulating rotavirus strains, to understand the effect of rotavirus variation on the efficacy of currently available vaccines. Abstracts for SupplementInternational Journal of Infectious DiseasesVol. 14Preview Full-Text PDF Open Archive
By the end of 2021, the Omicron variant of SARS-CoV-2, the coronavirus responsible for COVID-19, emerges, causing immediate concern, due to the explosive increase in cases in South Africa and a large number of mutations. This study describes the characteristic mutations of the Omicron variant in the Spike protein, and the behavior of the successive epidemic waves associated to the sub-lineages throughout the world. The mutations in the Spike protein described are related to the virus ability to evade the protec-tion elicited by current vaccines, as well as with possible reduced susceptibil-ity to host proteases for priming of the fusion process, and how this might be related to changes in tropism, a replication enhanced in nasal epithelial cells, and reduced in pulmonary tissue; traits probably associated with the apparent reduced severity of Omicron compared to other variants.
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