👤 Patrick Callier

The association of mucosal shedding of human simplex virus (HSV)-2, Kaposi's sarcoma-associated herpesvirus (KSHV) and cytomegalovirus (CMV) after antiretroviral therapy (ART) initiation in women-living-with-HIV (WLWH) with systemic inflammation is unclear. We recruited 187 ART-naive adult WLWH in south-central Uganda. HSV-1, HSV-2, CMV, and Varicella Zoster Virus (VZV) in vaginal secretions and Kaposi's sarcoma-associated herpesvirus (KSHV) in oral swabs were quantified by PCR. Plasma biomarkers of systemic inflammation were measured by ELISA or electrochemiluminescence before and after ART initiation (weeks 8, 12, and 24). Participants had a baseline median age of 28 years and CD4 count of 413 cells/μL. Viral shedding rates were similar for all tested viruses between baseline and post-ART timepoints in the overall study population. CMV shedding significantly increased from a baseline rate of 53% to 77% at week 4 visit ( Although ART initiation was not associated with increased herpesvirus shedding overall, CMV shedding increased in women with advanced HIV-1. The association of mucosal shedding of CMV, HSV-2, and KSHV in post-ART timepoints with different baseline biomarkers of systemic inflammation suggest that distinct immunological functions are implicated in the control of their viral replication. Show less

Balanced chromosomal rearrangements associated with abnormal phenotype are rare events, but may be challenging for genetic counselling, since molecular characterisation of breakpoints is not performed routinely. We used next-generation sequencing to characterise breakpoints of balanced chromosomal rearrangements at the molecular level in patients with intellectual disability and/or congenital anomalies. Breakpoints were characterised by a paired-end low depth whole genome sequencing (WGS) strategy and validated by Sanger sequencing. Expression study of disrupted and neighbouring genes was performed by RT-qPCR from blood or lymphoblastoid cell line RNA. Among the 55 patients included (41 reciprocal translocations, 4 inversions, 2 insertions and 8 complex chromosomal rearrangements), we were able to detect 89% of chromosomal rearrangements (49/55). Molecular signatures at the breakpoints suggested that DNA breaks arose randomly and that there was no major influence of repeated elements. Non-homologous end-joining appeared as the main mechanism of repair (55% of rearrangements). A diagnosis could be established in 22/49 patients (44.8%), 15 by gene disruption ( Paired-end WGS is a valid strategy and may be used for structural variation characterisation in a clinical setting. Show less