Recurrent Signature Patterns in HIV-1 B Clade Envelope Glycoproteins Associated with either Early or Chronic Infections

Here we have identified HIV-1 B clade Envelope (Env) amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To accomplish this, we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. Samples were divided at the outset into hypothesis-forming and validation sets, and we used phylogenetically corrected statistical strategies to identify signatures, systematically scanning all of Env. Signatures included single amino acids, glycosylation motifs, and multi-site patterns based on functional or structural groupings of amino acids. We identified signatures near the CCR5 co-receptor-binding region, near the CD4 binding site, and in the signal peptide and cytoplasmic domain, which may influence Env expression and processing. Two signatures patterns associated with transmission were particularly interesting. The first was the most statistically robust signature, located in position 12 in the signal peptide. The second was the loss of an N-linked glycosylation site at positions 413–415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies, consistent with enabling a common pathway for immune escape during chronic infection. Its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. The signature patterns we identified implicate Env expression levels in selection at viral transmission or in early expansion, and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response

The Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission.

The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared the replication of recombinant virus pairs carrying the full Env (Env viruses) or the Env ectodomain fused to the gp41CT of NL4.3 (EnvEC viruses) (12 subtype C and 10 subtype B pairs) in primary CD4+ T-cells and monocyte-derived-macrophages (MDMs). In CD4+ T-cells, replication was as follows: B-EnvEC = B-Env>C-EnvEC>C-Env, indicating that the gp41CT of subtype C contributes to the low replicative capacity of this subtype. In MDMs, in contrast, replication capacity was comparable for all viruses regardless of subtype and of gp41CT. In CD4+ T-cells, viral entry, viral release and viral gene expression were similar. However, infectivity of free virions and cell-to-cell transmission of C-Env viruses released by CD4+ T-cells was lower, suggestive of lower Env incorporation into virions. Subtype C matrix only minimally rescued viral replication and failed to restore infectivity of free viruses and cell-to-cell transmission. Taken together, these results show that polymorphisms in the gp41CT contribute to viral replication capacity and suggest that the number of Env spikes per virion may vary across subtypes. These findings should be taken into consideration in the design of vaccines

mHealth : a game-changer for multilingual service encounters?

In this chapter we report on recent research assessing the impact of m-health (mobile health) on meaning-making in multilingual health care settings (De Wilde, Van Praet & Van Vaerenbergh, 2019). We zoom in on the design, development and usability testing of a multilingual, mobile app to facilitate the communication between caretakers of a preventive health organisation situated in Flanders, Belgium and mothers with limited Dutch proficiency. The application runs on a Windows 10 touchscreen tablet, groups various communication support tools, such as translation in 5 foreign languages, pictograms, icons, video remote interpreting, and an audio version of text content. The chapter describes the results of a two-group between-subjects experiment, in which respondents (N=20) were randomly assigned to either a service encounter with app (N=11), or a service encounter without app (N=9). The research builds on the hypothesis that technological mediation facilitates the transfer of information. To verify this hypothesis, we rely on a mixed method approach, integrating quantitative and qualitative research methods: (i) SERVQUAL satisfaction questionnaires and (ii) Discourse Analysis, analyzing patterns of speech and interaction in a qualitative and semi-quantitative way, for example by measuring the length of pauses, or the amount of hand gestures. In particular, we investigate to which extent technological mediation promotes, advances and accelerates the clarification of complex, abstract notions. In doing so, we cross-compare service providers’ verbal and non-verbal behavior in technology-facilitated service encounters (11) and technology-free service encounters (9), scrutinizing the intensity, variety and accuracy in non-verbal cues, along with the time-span needed to explain difficult time-related concepts (e.g. patience). Gestures have been hypothesized to reduce demands on conceptualization, and speakers have been found to gesture more on problems that are conceptually difficult, even when lexical demands are equated (Hickock & Small, 2016). The assumption guiding our research, then, was that service providers would need less hand gestures and less time to explain a difficult concept, provided the app reduced the demands on conceptualization. Starting off by counting, coding and measuring the complete data set, we proceed to a detailed qualitative analysis of selected passages of video-recorded service-encounters in order to explore why, how and if the multimodality of the app exerts its influence on communication. Using a combination of qualitative and quantitative data improved our evaluation by ensuring that the limitations of one type of data were balanced by the strengths of another. The findings address concerns of lengthened visit time, reduced eye contact, reduced non-verbal intensity, and additional training needs. The paper closes with brief guidelines for unlocking the potential of mHealth in language discordant service encounters. We spell out implications for health care provision, the limitations of our approach, and avenues for future research (see also De Wilde, Van Praet & Rillof, 2016). In doing so, we zoom out on the increasing importance of assessing service quality in industries where customer involvement is high, such as healthcare and financial services. We reflect on language as a resource in the globalized new economy, and how this is a critical given in extending the focus of linguistic research (Heller 2010)