Herpesvirus Replication Compartments: Dynamic Biomolecular Condensates?

Recent progress has provided clear evidence that many RNA-viruses form cytoplasmic biomolecular condensates mediated by liquid–liquid phase separation to facilitate their replication. In contrast, seemingly contradictory data exist for herpesviruses, which replicate their DNA genomes in nuclear membrane-less replication compartments (RCs). Here, we review the current literature and comment on nuclear condensate formation by herpesviruses, specifically with regard to RC formation. Based on data obtained with human cytomegalovirus (human herpesvirus 5), we propose that liquid and homogenous early RCs convert into more heterogeneous RCs with complex properties over the course of infection. We highlight how the advent of DNA replication leads to the maturation of these biomolecular condensates, likely by adding an additional DNA scaffold.     

SARS-CoV-2 Specific Immune Response and Inflammatory Profile in Advanced HIV-Infected Persons during a COVID-19 Outbreak

The main aim of this study was to describe the clinical and immunological outcomes, as well as the inflammatory profile, of patients with advanced HIV in an assisted-living facility in which an outbreak of SARS-CoV-2 occurred. SARS-CoV-2 humoral and specific T-cell response were analyzed in patients with HIV infection and COVID-19; as a secondary objective of the analysis, levels of the inflammatory markers (IL-1β, IL-6, IL-8, and TNFα) were tested in the HIV/COVID-19 group, in HIV-positive patients without COVID-19, and in HIV-negative patients with mild/moderate COVID-19. Antibody kinetics and ability to neutralize SARS-CoV-2 were evaluated by ELISA assay, as well as the inflammatory cytokines; SARS-CoV-2 specific T-cell response was quantified by ELISpot assay. Mann–Whitney or Kruskal–Wallis tests were used for comparisons. Thirty patients were included with the following demographics: age, 57 years old (IQR, 53–62); 76% male; median HIV duration of infection, 18 years (15–29); nadir of CD4, 57/mmc (23–100) current CD4 count, 348/mmc (186–565). Furthermore, 83% had at least one comorbidity. The severity of COVID-19 was mild/moderate, and the overall mortality rate was 10% (3/30). Additionally, 90% of patients showed positive antibody titers and neutralizing activity, with a 100% positive SARS-CoV-2 specific T-cell response over time, suggesting the ability to induce an effective specific immunity. Significantly higher levels of IL-6, IL-8, and TNF-α in COVID-19 without HIV vs. HIV/COVID-19 patients (p < 0.05) were observed. HIV infection did not seem to negatively impact COVID-19-related inflammatory state and immunity. Further data are mandatory to evaluate the persistence of these immunity and its ability to expand after exposure and/or vaccination.     

Mast cells and tumour angiogenesis: new insight from experimental carcinogenesis

Histopathologic examination and clinical observations of solid and haematological malignancies indicates mast cells as key host cells in the tumour infiltrate, with important consequence on tumour-associated angiogenesis and tumour growth. Data suggest indeed that tumour-infiltrating mast cells may exert a prominent function in the angiogenic "switch", which is essential for the progression of early tumours. The experimental approach has substantially increased our understanding of the role of tumour-infiltrating mast cells in the process of angiogenesis that accompanies tumour development. This review will focus on the crucial contribution of mast cells in promoting tumour neovascularization as it emerges from the most recent observations of experimental carcinogenesis in in vivo and in vitro models.     

In utero acquired limb ischemia in monochorionic twins with and without twin-to-twin transfusion syndrome

OBJECTIVE: To report on the occurrence of in utero acquired limb ischemia in two referral institutions managing monochorionic (MC) twins with and without twin-to-twin transfusion syndrome (TTTS) and estimate its prevalence. METHODS: All MC twin pregnancies assessed at two referral units between 2002 and 2007 were retrospectively reviewed for the presence of in utero acquired limb ischemia. RESULTS: A total of 391 MC twin pairs with TTTS and 384 MC twin pairs without TTTS were included. The prevalence of in utero acquired limb ischemia in MC twin pairs was 0.52% (4/775). An ischemic defect of the right upper limb was detected in two recipient twins in the TTTS group, whereas an ischemic defect of the right lower limb was found in two infants in the group without TTTS. CONCLUSION: In utero acquired limb ischemia may occur in MC twins with TTTS and without TTTS. In TTTS, we only observed this event in recipient twins. In our experience, its prevalence was higher than in the general population. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Modeling severely discordant hematocrits and normal amniotic fluids after incomplete laser therapy in twin-to-twin transfusion syndrome

Our objective was to explain the clinical presentations of sustained arteriovenous anastomotic transfusion of blood after incomplete laser therapy in twin-to-twin transfusion syndrome (TTTS). We extended our mathematical model of TTTS by adding the dynamics of hematocrit, and simulated incomplete laser therapy, first, by leaving one patent opposite arteriovenous anastomosis from the recipient to the donor and, second, by leaving one patent arteriovenous anastomosis from the donor to the recipient. In both simulations we reproduced the clinical observation of severe hematocrit discordance preceding delayed amniotic fluid imbalance. In conclusion, incomplete laser therapy may cause a severe circulatory imbalance between the twins which presents predominantly as discordant hematocrits rather than discordant amniotic fluid volumes as in primary TTTS. These results imply that the anemia-polycythemia sequence is a sensitive mechanism to identify transfusion reversal after complicated laser therapy, confirming the suggested role of middle cerebral artery peak systolic velocity Doppler measurements as a useful method of follow-up.