Diminished placental Factor XIIIA1 expression associates with pre-conception antiretroviral treatment and preterm birth in pregnant people living with HIV.

We previously showed a link between maternal vascular malperfusion and pre-term birth (PTB) in pregnant people living with HIV (PPLH) initiating antiretroviral treatment (ART) before pregnancy, indicating poor placental vascularisation. After measuring antenatal plasma angiogenic factors to seek mechanistic insights, low levels of plasma Factor XIIIA1 (FXIIIA1) and vascular-endothelial-growth-factor (VEGF) was significantly associated with PTB at the time closest to delivery (median 34 weeks) in PPLH initiating ART before pregnancy. Knowing that FXIIIA1 is crucial for haemostasis, angiogenesis, implantation and pregnancy maintenance and that expression is found on placental macrophages (Hofbauer cells), we examined placentae at delivery from matching participants who either initiating ART before pregnancy or during gestation.

HIV-1 subtype C Nef-mediated SERINC5 down-regulation significantly contributes to overall Nef activity.

Background: Nef performs multiple cellular activities that enhance HIV-1 pathogenesis. The role of Nef-mediated down-regulation of the host restriction factor SERINC5 in HIV-1 pathogenesis is not well-defined. We aimed to investigate if SERINC5 down-regulation activity contributes to HIV-1 subtype C disease progression, to assess the relative contribution of this activity to overall Nef function, and to identify amino acids required for optimal activity.

Vulnerable targets in HIV-1 Pol for attenuation-based vaccine design.

Identification of viral immune escape mutations that compromise HIV's ability to replicate may aid rational attenuation-based vaccine design. Previously we reported amino acids associated with altered viral replication capacity (RC) from a sequence-function analysis of 487 patient-derived RT-integrase sequences. In this study, site-directed mutagenesis experiments were performed to validate the effect of these mutations on RC.

Association between the cytokine storm, immune cell dynamics, and viral replicative capacity in hyperacute HIV infection.

Introduction: Immunological damage in acute HIV infection (AHI) may predispose to detrimental clinical sequela. However, studies on the earliest HIV-induced immunological changes are limited, particularly in sub-Saharan Africa. We assessed the plasma cytokines kinetics, and their associations with virological and immunological parameters, in a well-characterized AHI cohort where participants were diagnosed before peak viremia.

Pol-Driven Replicative Capacity Impacts Disease Progression in HIV-1 Subtype C Infection.

CD8 T cell-mediated escape mutations in Gag can reduce HIV-1 replication capacity (RC) and alter disease progression, but less is known about immune-mediated attenuation in other HIV-1 proteins. We generated 487 recombinant viruses encoding RT-integrase from individuals with chronic ( = 406) and recent ( = 81) HIV-1 subtype C infection and measured their RC using a green fluorescent protein (GFP) reporter T cell assay. In recently infected individuals, reverse transcriptase (RT)-integrase-driven RC correlated significantly with viral load set point ( 0.