RESUMEN
Chagas disease affects around 8 million people globally, with Latin America bearing approximately 10,000 deaths each year. Combatting the disease relies heavily on vector control methods, necessitating the identification of new targets. Within insect genomes, genes harboring small open reading frames (smORFs - < 100 amino acids) present numerous potential candidates. In our investigation, we elucidate the pivotal role of the archetypal smORF-containing gene, mille-pattes/polished-rice/tarsalless (mlpt/pri/tal), in the post-embryonic development of the kissing bug Rhodnius prolixus. Injection of double-stranded RNA targeting mlpt (dsmlpt) during nymphal stages yields a spectrum of phenotypes hindering post-embryonic growth. Notably, fourth or fifth stage nymphs subjected to dsmlpt do not undergo molting. These dsmlpt nymphs display heightened mRNA levels of JHAMT-like and EPOX-like, enzymes putatively involved in the juvenile hormone (JH) pathway, alongside increased expression of the transcription factor Kr-h1, indicating changes in the hormonal control. Histological examination reveals structural alterations in the hindgut and external cuticle of dsmlpt nymphs compared to control (dsGFP) counterparts. Furthermore, significant changes in the vector's digestive physiology were observed, with elevated hemozoin and glucose levels in the posterior midgut of dsmlpt nymphs. Importantly, dsmlpt nymphs exhibit impaired metacyclogenesis of Trypanosoma cruzi, the causative agent of Chagas disease, underscoring the crucial role of proper gut organization in parasite differentiation. Thus, our findings constitute the first evidence of a smORF-containing gene's regulatory influence on vector physiology, parasitic cycle, and disease transmission.
Asunto(s)
Proteínas de Insectos , Muda , Ninfa , Rhodnius , Animales , Rhodnius/genética , Rhodnius/fisiología , Rhodnius/crecimiento & desarrollo , Ninfa/crecimiento & desarrollo , Ninfa/genética , Ninfa/fisiología , Muda/genética , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Hormonas Juveniles/metabolismo , Sistemas de Lectura Abierta , DigestiónRESUMEN
Introduction: A characteristic of the COVID-19 pandemic has been the sequential emergence and global dissemination of SARS-CoV-2 variants, noted for their enhanced transmission efficiency. These variants with mutations in the Spike glycoprotein (S-glycoprotein), which interacts with ACE2 receptors in human cells is critical for infection, affects the transmissibility of the virus, which is a matter of great concern for public health. Objective: This research analyses the effects these variants on a cohort of vaccinated and naturally infected individuals from the cities of Macaé-RJ, Rio das Ostras-RJ, and Campos dos Goytacazes-RJ, Brazil, from March 2021 to March 2023. Methods: This investigation encompasses the Alpha (B.1.1.7), Gamma (P.1), Delta (B.1.617.2, B.1.671.3), and Omicron (BQ.1, BQ.1.1 sublines, and BF.7) variants, focusing on their genomic surveillance and implications for the disease's epidemiology. The experimental analysis included a control group (vaccinated and uninfected subjects), and an infected group (post-vaccinated subjects). Samples from nasopharyngeal swabs underwent viral detection via RT-qPCR for diagnosis confirmation. RNase H-dependent RT-qPCR (rhAmp-PCR) and third-generation sequencing were used to detect SARS-CoV-2 variants. Anti-S-glycoprotein immunoglobulins were also evaluated for vaccinated infected and noninfected volunteers. Symptoms from infected individuals were compiled in order to reveal patterns of clinical signs associated with viral infection. Results: The study included 289 participants, with infections identified by Gamma (n = 44), Delta (n = 189), and Omicron (n = 56) variants. The prevalent symptoms among the naturally infected participants were cough, fever, sore throat, headache, and runny nose. For Omicron, cognitive symptoms such as memory loss and concentration issues were reported. Interestingly, the infected vaccinated group had higher anti-S-glycoprotein IgM production (n = 28, 0.2833 ± 0.09768 OD) compared to the uninfected vaccinated group (n = 14, 0.1035 ± 0.03625 OD). Conversely, anti-S-glycoprotein IgG production was higher in the control group (n = 12, 1.770 ± 0.1393 OD) than in the infected vaccinated group (n = 26, 1.391 ± 0.1563 OD). Conclusion: This comprehensive study enables monitoring of predominant variants and their correlation with clinical cases, providing valuable insights for public health. Our research group continues to survey circulating variants, contributing to the global understanding of the pandemic.