The metabolism of small cellular RNA species during productive subgroup C adenovirus infection

AbstractDuring the late phase of subgroup C adenovirus infection, export of cellular mRNA from the nucleus to the cytoplasm isinhibited. In one approach to investigate the mechanism whereby viral late mRNAs are selected for export, we have examined the metabolism of small cellular RNA species transcribed by all three RNA polymerases during the late phase of Ad5 infection. No changes in the quantities of [3H]uridine-labeled 5S rRNA or tRNAs entering the cytoplasm were observed in infected cells. Adenovirus type 5 infection reduced the nuclear and cytoplasmic populations of the newly synthesized, snRNP-associated snRNAs U1, U2, U4, U5, and U6. Transcription of a representative snRNA, U1 RNA, was not inhibited, indicating that the post-transcriptional metabolism of snRNAs was perturbed during the late phase of infection. The increased cytoplasmic concentration of newly synthesized U1 RNA in Ad5- compared to mock-infected cells, and the greater reduction of the snRNP-associated compared to the total U1 RNA population, indicated that snRNP assembly in the cytoplasm was impaired. As adenovirus infection does not perturb export from the nucleus of small cellular mRNAs transcribed by RNA polymerases II and III, viral mRNA must be distinguished for selective export at a nuclear step upstream of translocation to the cytoplasm via nuclear pore complexes

The Effects of Loaded Fatigue on Loaded Postural Stability

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Multi-stakeholder consensus on a target product profile for an HIV cure

Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures

Multi-stakeholder consensus on a target product profile for an HIV cure

Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures