Thriving under Stress: Selective Translation of HIV-1 Structural Protein mRNA during Vpr-Mediated Impairment of eIF4E Translation Activity

Translation is a regulated process and is pivotal to proper cell growth and homeostasis. All retroviruses rely on the host translational machinery for viral protein synthesis and thus may be susceptible to its perturbation in response to stress, co-infection, and/or cell cycle arrest. HIV-1 infection arrests the cell cycle in the G2/M phase, potentially disrupting the regulation of host cell translation. In this study, we present evidence that HIV-1 infection downregulates translation in lymphocytes, attributable to the cell cycle arrest induced by the HIV-1 accessory protein Vpr. The molecular basis of the translation suppression is reduced accumulation of the active form of the translation initiation factor 4E (eIF4E). However, synthesis of viral structural proteins is sustained despite the general suppression of protein production. HIV-1 mRNA translation is sustained due to the distinct composition of the HIV-1 ribonucleoprotein complexes. RNA-coimmunoprecipitation assays determined that the HIV-1 unspliced and singly spliced transcripts are predominantly associated with nuclear cap binding protein 80 (CBP80) in contrast to completely-spliced viral and cellular mRNAs that are associated with eIF4E. The active translation of the nuclear cap binding complex (CBC)-bound viral mRNAs is demonstrated by ribosomal RNA profile analyses. Thus, our findings have uncovered that the maintenance of CBC association is a novel mechanism used by HIV-1 to bypass downregulation of eIF4E activity and sustain viral protein synthesis. We speculate that a subset of CBP80-bound cellular mRNAs contribute to recovery from significant cellular stress, including human retrovirus infection

Children coping with COVID-19: Intersectional understandings of film and media access in a crisis

As a result of the global COVID-19 pandemic and resulting lockdowns across the world, digital access has become paramount, as most aspects of education have moved online. Drawing together five case studies located in South Africa, Argentina, the Netherlands, India and Ethiopia, this article assesses the role of film education during the COVID-19 pandemic, with a specific focus on the impacts of digital access. We examine multimodal forms of film education, and how these were used to inform, entertain and educate children during the crisis by the varying work undertaken by the organizations. Applying theories of intersectionality, we address the need for context-specific approaches to film education, focusing upon the impact that the societal and individual contexts had on the dissemination of film education in each country

Changing trend of HIV, Syphilis and Hepatitis C among Men Who Have Sex with Men in China

Dearth of information regarding the trend and correlates of HIV, syphilis and Hepatitis C (HCV) in a country-wide sample of understudied though high-risk Chinese men who have sex with men (MSM) called for a comprehensive serial cross-sectional study. Using a multistage mixed-method strategy, 171,311 MSM from 107 selected cities/counties in 30 provinces of mainland China, were interviewed and tested. Descriptive, bivariate, multivariate and Cochran-Armitage trend analyses were conducted using SAS 9.2. During 2009-13, recent (71.5% to 78.6%, p < 0.001) and consistent (40.4% to 48.8%, p < 0.001) condom use as well as condom use during commercial anal sex (46.5% to 55.0%, p < 0.001) were increasing. In contrast, commercial anal sex with male (11.9% to 7.1%, p < 0.001) and drug use (1.9% to 0.8%, p < 0.001) were decreasing over time. HIV prevalence increased gradually (5.5% to 7.3%, p < 0.001), while syphilis (9.0% to 6.3%, p < 0.001) and HCV prevalence (1.5% to 0.7%, p < 0.001) decreased over time. A positive correlation was observed between HIV and syphilis prevalence (r = 0.38). HIV infection was associated with HIV-related knowledge, services and injecting drug use. An increasing trend of HIV prevalence was observed during 2009–13 among MSM in China. While gradual reduction of risk behaviors along with syphilis and HCV prevalence supported expansion of testing and prevention services, increasing HIV burden called for deeper thematic investigations

KCNJ15/Kir4.2 couples with polyamines to sense weak extracellular electric fields in galvanotaxis

Weak electric fields guide cell migration, known as galvanotaxis/electrotaxis. The sensor(s) cells use to detect the fields remain elusive. Here we perform a large-scale screen using an RNAi library targeting ion transporters in human cells. We identify 18 genes that show either defective or increased galvanotaxis after knockdown. Knockdown of the KCNJ15 gene (encoding inwardly rectifying K(+) channel Kir4.2) specifically abolishes galvanotaxis, without affecting basal motility and directional migration in a monolayer scratch assay. Depletion of cytoplasmic polyamines, highly positively charged small molecules that regulate Kir4.2 function, completely inhibits galvanotaxis, whereas increase of intracellular polyamines enhances galvanotaxis in a Kir4.2-dependent manner. Expression of a polyamine-binding defective mutant of KCNJ15 significantly decreases galvanotaxis. Knockdown or inhibition of KCNJ15 prevents phosphatidylinositol 3,4,5-triphosphate (PIP(3)) from distributing to the leading edge. Taken together these data suggest a previously unknown two-molecule sensing mechanism in which KCNJ15/Kir4.2 couples with polyamines in sensing weak electric fields