TRBP and eIF6 Homologue in Marsupenaeus japonicus Play Crucial Roles in Antiviral Response

Plants and invertebrates can suppress viral infection through RNA silencing, mediated by RNA-induced silencing complex (RISC). Trans-activation response RNA-binding protein (TRBP), consisting of three double-stranded RNA-binding domains, is a component of the RISC. In our previous paper, a TRBP homologue in Fenneropenaeus chinensis (Fc-TRBP) was reported to directly bind to eukaryotic initiation factor 6 (Fc-eIF6). In this study, we further characterized the function of TRBP and the involvement of TRBP and eIF6 in antiviral RNA interference (RNAi) pathway of shrimp. The double-stranded RNA binding domains (dsRBDs) B and C of the TRBP from Marsupenaeus japonicus (Mj-TRBP) were found to mediate the interaction of TRBP and eIF6. Gel-shift assays revealed that the N-terminal of Mj-TRBP dsRBD strongly binds to double-stranded RNA (dsRNA) and that the homodimer of the TRBP mediated by the C-terminal dsRBD increases the affinity to dsRNA. RNAi against either Mj-TRBP or Mj-eIF6 impairs the dsRNA-induced sequence-specific RNAi pathway and facilitates the proliferation of white spot syndrome virus (WSSV). These results further proved the important roles of TRBP and eIF6 in the antiviral response of shrimp

Esofagites em pacientes com síndrome de imunodeficiência adquirida: estudo histológico e imunoistoquímico Esophagitis in patients with acquired human immunodeficiency syndrome: an histological and immunohistochemistry study

RACIONAL: A maioria dos pacientes com síndrome da imunodeficiência adquirida cursa com sintomas gastrointestinais ao longo da sua evolução. A alta prevalência e morbidade das esofagites nesses pacientes são amplamente reconhecidas. OBJETIVOS: Graduar, histologicamente, as esofagites; identificar os agentes associados, tais como Candida sp, citomegalovírus, herpes vírus e micobactérias; identificar, através da imunoistoquímica, os seguintes agentes: citomegalovírus, herpes vírus I e II, vírus Epstein-Barr, vírus do papiloma humano e vírus da imunodeficiência adquirida; verificar a contribuição da imunoistoquímica para o diagnóstico dos agentes infecciosos; verificar a associação entre os achados histológicos e endoscópicos; verificar a relevância do número de fragmentos na caracterização dos agentes etiológicos. MÉTODOS: Estudaram-se, retrospectivamente, biopsias esofagianas em 227 pacientes com síndrome da imunodeficiência adquirida. Utilizaram-se as colorações de hematoxilina e eosina, PAS ("periodic acid of Schiff"), prata de Grocott e Ziehl-Nielsen, assim como a imunoistoquímica para a detecção de infecções por agentes oportunistas. Aspectos endoscópicos também foram avaliados. RESULTADOS: A esofagite inespecífica acentuada, localizada no terço inferior, foi o tipo mais freqüente. A Candida sp foi o agente mais encontrado, seguida de citomegalovírus, herpes vírus e micobactérias. A presença de placa e ulceração sugeriu o diagnóstico de candidíase e esofagite por citomegalovírus, respectivamente. O herpes vírus I não foi encontrado isolado e sim associado ao herpes vírus II. Não houve imunorreatividade para o vírus Epstein-Barr e o vírus da imunodeficiência adquirida. O número de fragmentos nas amostras não influenciou na detecção do agente etiológico. CONCLUSÃO: Os achados endoscópicos de lesão em placa ou de úlcera estão associados com os diagnósticos de Candida sp e citomegalovírus, respectivamente. O emprego da técnica de imunoistoquímica auxilia no diagnóstico das esofagites virais e torna possível detectar o citomegalovírus em esôfagos normais à endoscopia e/ou ao exame histopatológico.<br>BACKGROUND: Almost all patients with acquired immunodeficiency virus syndrome will have gastrointestinal symptoms during the course of their illness. The high prevalence and complications of esophagitis are well documented. AIM: Graduate esophagitis; identify microorganisms like Candida sp, cytomegalovirus, herpesvirus and mycobacteria; identify by immunohistochemical staining viral agents cytomegalovirus, herpesvirus I, herpesvirus II, Epstein-Barr Virus, human papilloma virus and human immunodeficiency virus; verify how immunohistochemistry changes the profile of esophagitis; verify the association between the histological and endoscopical findings; verify the relevance of the number of fragments studied in the characterization of the histological agents. METHODS: We studied retrospectively esophageal biopsies in 227 patients with acquired immunodeficiency virus syndrome using hematoxylin and eosin, PAS (periodic acid of Schiff), Groccott and Ziehl-Nielsen stains and immunoperoxidase stains to detect opportunistic agents. Endoscopic aspects were studied. RESULTS: The non-specific esophagitis grade III, in the inferior third of the esophagus, was the most frequent type. Candida sp was the most frequent agent, followed by viruses cytomegalovirus, herpesvirus and mycobacteria. The presence of plaque and ulceration suggested the diagnosis of esophageal candidiasis and cytomegalovirus esophagitis. Immunohistochemical allowed the characterization of cytomegalovirus and of herpesvirus in those cases where other techniques could not achieve it, furthermore the cytomegalovirus was also found in histological normal cases, making the use of this technique advisable in routine diagnosis. The herpesvirus I was not found isolated but associated to herpesvirus II. We have not found immunoreactivity for the Epstein-Barr virus and the human immunodeficiency virus. The number of fragments does not seem to influence the detection of the etiologic agent. CONCLUSION: The endoscopic findings of plaques or ulcers are associated with candidiasis or cytomegalovirus esophagitis. Immunohistochemisty improved the diagnosis of viral infections. It is possible to detect cytomegalovirus infections in endoscopic and histologic normal cases

Antiretroviral therapy and preterm birth in HIV-infected women

The use of combination antiretroviral therapy for the prevention of mother to child transmission of HIV infection has achieved vertical HIV transmission rates of <1%. The use of these drugs is not without risk to the mother and infant. Pregnant women with HIV-infection are at high risk of preterm birth (PTB <37 weeks), with 2–4-fold the risk of uninfected women. There is accumulating evidence that certain combinations are associated with higher rates of PTB that others or no antiretroviral treatment. Understanding the pathogenesis of PTB in this group of women will be essential to target preventative strategies in the face of increasing HIV prevalence and rapidly expanding mother-to-child-transmission prevention programmes

RNA recognition by double-stranded RNA binding domains: a matter of shape and sequence

The double stranded RNA binding domain (dsRBD) is a small protein domain of 65–70 amino acids adopting an αβββα fold, whose central property is to bind to double stranded RNA (dsRNA). This domain is present in proteins implicated in many aspects of cellular life, including antiviral response, RNA editing, RNA processing, RNA transport and last but not least RNA silencing. Even though proteins containing dsRBDs can bind to very specific dsRNA targets in vivo, the binding of dsRBDs to dsRNA is commonly believed to be shape-dependent rather than sequence-specific. Interestingly, recent structural information on dsRNA recognition by dsRBDs opens the possibility that this domain performs a direct readout of RNA sequence in the minor groove, allowing a global reconsideration of the principles describing dsRNA recognition by dsRBDs. We review in this article the current structural and molecular knowledge on dsRBDs emphasizing the intricate relationship between the amino acid sequence, the structure of the domain and its RNA recognition capacity. We especially focus on the molecular determinants of dsRNA recognition and describe how sequence discrimination can be achieved by this type of domain