Identification of a protein encoded in the EB-viral open reading frame BMRF2

Using monospecific rabbit sera against a peptide derived from a potential antigenic region of the Epstein-Barr viral amino acid sequence encoded in the open reading frame BMRF2 we could identify a protein-complex of 53/55 kDa in chemically induced B95-8, P3HR1 and Raji cell lines. This protein could be shown to be membrane-associated, as predicted by previous computer analysis of the secondary structure and hydrophilicity pattern, and may be a member of EBV-induced membrane proteins in lytically infected cells

Promoting Engagement With a Digital Health Intervention (HeLP-Diabetes) Using Email and Text Message Prompts: Mixed-Methods Study

BACKGROUND: Engagement with digital health interventions (DHIs) may be regarded as a prerequisite for the intervention to achieve positive health or behavior change outcomes. One method employed to promote engagement is the use of prompts such as emails and text messages. However, little is known about the characteristics of prompts that promote engagement. This study explored the association between the content and delivery mode of prompts and the users' engagement with HeLP-Diabetes (Healthy Living for People with type 2 Diabetes), a DHI that aimed to promote self-management in adults with type 2 diabetes. OBJECTIVE: The objective of this study was to identify the characteristics of prompts, specifically the content and delivery mode, which were associated with increased engagement. METHODS: This was a mixed-methods study. Email and text message prompts were sent to the registered users of HeLP-Diabetes. Use of the intervention was recorded and examined to identify which email and text message prompts were associated with subsequent visits to the DHI. Characteristics of prompts that were identified as particularly effective or ineffective were explored through think-aloud interviews with the participants. RESULTS: Of a total of 39 email prompts, 49% (19/39) prompts showed a significant association with subsequent visits to the DHI. However, none of the text message prompts were associated with subsequent visits to the DHI. Furthermore, think-aloud interviews were carried out with 6 experienced participants with type 2 diabetes. The findings suggest that these participants preferred email prompts that were clear, relatively short, and empowering; used nondirective advice; included health professional references; were visually appealing; and contained news and updates. CONCLUSIONS: The findings of this study contribute to the existing evidence supporting the role of email prompts in promoting and maintaining engagement with DHIs. This study described the content of prompts that may be engaging. However, the results should be interpreted with caution, as prompts may be context-specific interventions and the results may not be generalizable across other DHIs or other types of interventions targeting self-management of type 2 diabetes

Deep Sequencing Reveals Direct Targets of Gammaherpesvirus-Induced mRNA Decay and Suggests That Multiple Mechanisms Govern Cellular Transcript Escape

One characteristic of lytic infection with gammaherpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and murine herpesvirus 68 (MHV68), is the dramatic suppression of cellular gene expression in a process known as host shutoff. The alkaline exonuclease proteins (KSHV SOX, MHV-68 muSOX and EBV BGLF5) have been shown to induce shutoff by destabilizing cellular mRNAs. Here we extend previous analyses of cellular mRNA abundance during lytic infection to characterize the effects of SOX and muSOX, in the absence of other viral genes, utilizing deep sequencing technology (RNA-seq). Consistent with previous observations during lytic infection, the majority of transcripts are downregulated in cells expressing either SOX or muSOX, with muSOX acting as a more potent shutoff factor than SOX. Moreover, most cellular messages fall into the same expression class in both SOX- and muSOX-expressing cells, indicating that both factors target similar pools of mRNAs. More abundant mRNAs are more efficiently downregulated, suggesting a concentration effect in transcript targeting. However, even among highly expressed genes there are mRNAs that escape host shutoff. Further characterization of select escapees reveals multiple mechanisms by which cellular genes can evade downregulation. While some mRNAs are directly refractory to SOX, the steady state levels of others remain unchanged, presumably as a consequence of downstream effects on mRNA biogenesis. Collectively, these studies lay the framework for dissecting the mechanisms underlying the susceptibility of mRNA to destruction during lytic gammaherpesvirus infection

HIV-1 Envelope Subregion Length Variation during Disease Progression

The V3 loop of the HIV-1 Env protein is the primary determinant of viral coreceptor usage, whereas the V1V2 loop region is thought to influence coreceptor binding and participate in shielding of neutralization-sensitive regions of the Env glycoprotein gp120 from antibody responses. The functional properties and antigenicity of V1V2 are influenced by changes in amino acid sequence, sequence length and patterns of N-linked glycosylation. However, how these polymorphisms relate to HIV pathogenesis is not fully understood. We examined 5185 HIV-1 gp120 nucleotide sequence fragments and clinical data from 154 individuals (152 were infected with HIV-1 Subtype B). Sequences were aligned, translated, manually edited and separated into V1V2, C2, V3, C3, V4, C4 and V5 subregions. V1-V5 and subregion lengths were calculated, and potential N-linked glycosylation sites (PNLGS) counted. Loop lengths and PNLGS were examined as a function of time since infection, CD4 count, viral load, and calendar year in cross-sectional and longitudinal analyses. V1V2 length and PNLGS increased significantly through chronic infection before declining in late-stage infection. In cross-sectional analyses, V1V2 length also increased by calendar year between 1984 and 2004 in subjects with early and mid-stage illness. Our observations suggest that there is little selection for loop length at the time of transmission; following infection, HIV-1 adapts to host immune responses through increased V1V2 length and/or addition of carbohydrate moieties at N-linked glycosylation sites. V1V2 shortening during early and late-stage infection may reflect ineffective host immunity. Transmission from donors with chronic illness may have caused the modest increase in V1V2 length observed during the course of the pandemic