Host cell lectins ASGR1 and DC-SIGN jointly with TMEM106B confer ACE2 independence and imdevimab resistance to SARS-CoV-2 pseudovirus with spike mutation E484D.

The naturally occurring mutation E484D in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can render viral entry ACE2 independent and imdevimab resistant. Here, we investigated whether the cellular proteins ASGR1, DC-SIGN, and TMEM106B, which interact with the viral S protein, can contribute to these processes. Employing S protein-pseudotyped particles, we found that expression of ASGR1 or DC-SIGN jointly with TMEM106B allowed for robust entry of mutant E484D into otherwise non-susceptible cells, while this effect was not observed upon separate expression of the single proteins and upon infection with SARS-CoV-2 wild type (WT).

Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.

The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer.

Prevalence of probable post-traumatic stress disorder and experiences of trauma in emerging adults living with HIV in Zimbabwe.

Background: Little is known about the prevalence of post-traumatic stress disorder (PTSD) in emerging adults living with HIV in low-income countries.

Aims: Determine prevalence of trauma exposure, prevalence of probable PTSD and conditional prevalence of probable PTSD for different traumatic events; and better understand the experiences of individuals with HIV and PTSD.

Method: This mixed method study used secondary data from a cross-sectional survey of people ( = 222) aged 18 to 29 living with HIV in Zimbabwe and primary qualitative data collection.

Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies.

Hepatitis C virus (HCV) infection causes ~290,000 annual human deaths despite the highly effective antiviral treatment available. Several viral immune evasion mechanisms have hampered the development of an effective vaccine against HCV, among them the remarkable conformational flexibility within neutralization epitopes in the HCV antigens. Here, we report the design of epitope-focused immunogens displaying two distinct HCV cross-neutralization epitopes.

Association of Clinical, Biomechanical, and Psychosocial Factors with Smile Dynamics in Unilateral Cleft Lip: A Multicenter Observational Study.

Objective: To investigate the association between clinical, biomechanical, and psychosocial factors and smiling behavior in individuals with treated unilateral cleft lip with or without cleft palate (UCL ± P) compared to non-cleft controls.

Design: Multicenter observational study in New Zealand.

Participants: Individuals aged ≥15 ( = 42) comprised 2 study groups: a UCL ± P group ( = 21) and a non-cleft control group ( = 21).