HIV-1 sequences isolated from patients promote expression of shorter isoforms of the Gag polyprotein

International audienceHuman immunodeficiency virus type 1 (HIV-1) unspliced mRNA drives the expression of both Gag and Gag-Pol polyproteins by using both cap- and internal ribosome entry site (IRES)-dependent translation initiation mechanisms. An IRES has been described in the matrix coding region that is involved in the production of shorter isoforms of Gag. However, up to now, this has only been shown with sequences derived from the HIV-1 laboratory strains (NL4.3 and HXB2) and never from clinical HIV-1 isolates. We have isolated ~70 sequences from HIV-1-positive patients that we have sequenced and cloned into an expression vector to monitor their ability to drive translation of Gag p55 and the shorter isoforms both in vitro and ex vivo. The results indicate that (1) the translational efficiency from the AUG-p55 varies significantly among the different isolates; (2) expression initiated at AUG-p40 codon is independent of translation initiation at the AUG-p55 triplet; and (3) all sequences promote expression of shorter Gag isoforms, in particular in Jurkat T cells, in which internal initiation occurs exclusively and directly at the AUG-p40 codon. The composition of the first ~800 nucleotides of the HIV-1 unspliced mRNA modulates the expression initiated both at the AUG-p55 and AUG-p40 codons and may impact viral production and replication. Interestingly, the AUG-p40 codon and its surrounding nucleotide context are conserved amongst clinical isolates and are used as a translation initiation site to produce a shorter Gag isoform

Recovery From COVID-19-Related Olfactory Disorders and Quality of Life: Insights From an Observational Online Study

International audienceAbstract Although olfactory disorders (OD) are among the most significant symptoms of COVID-19, recovery time from COVID-19-related OD and their consequences on the quality of life remain poorly documented. We investigated the characteristics and behavioral consequences of COVID-19-related OD using a large-scale study involving 3111 French respondents (78% women) to an online questionnaire over a period of 9 months covering different epidemic waves (from 8 April 2020 to 13 January 2021). In the patients who subjectively recovered from COVID-19-related OD (N = 609), recovery occurred on average after 16 days and most of the time within 1 month (“normal” recovery range); 49 subjectively recovered in 1–2.5 months, and several cases took up to 6.5 months. Among the patients with ongoing OD (N = 2502), 974 were outside the “normal” recovery range (persistent OD) and reported OD for 1–10 months. Developing a persistent OD was more likely with increasing age and in women and was more often associated with parosmia and phantosmia. The deleterious impact of COVID-19-related OD on the quality of life was significantly aggravated by OD duration and was more pronounced in women. Because persistent OD is not infrequent after COVID-19, has deleterious consequences on the quality of life, and receives few solutions from the health practitioners, it would be beneficial to implement screening and treatment programs to minimize the long-term behavioral consequences of COVID-19-related OD

Identification of the needs of individuals affected by COVID-19

International audienceBackground: The optimal management of COVID-19 symptoms and their sequelae remains an important area of clinical research. Policy makers have little scientific data regarding the effects on the daily life of affected individuals and the identification of their needs. Such data are needed to inform effective care policy.Methods: We studied 639 people with COVID-19 resident in France via an online questionnaire. They reported their symptoms, effects on daily life, and resulting needs, with particular focus on olfaction.Results: The results indicate that a majority of participants viewed their symptoms as disabling, with symptoms affecting their physical and mental health, social and professional lives. 60% of the individuals reported having unmet medical, psychological and socio-professional support needs. Finally, affected individuals were concerned about the risk and invasiveness of possible treatments as shown by a preference for non-invasive intervention over surgery to cure anosmia.Conclusions:It is important that policy makers take these needs into consideration in order to assist affected individuals to regain a normal quality of life