Correction: Molecular modelling of the HCMV IL-10 protein isoforms and analysis of their interaction with the human IL-10 receptor.

[This corrects the article DOI: 10.1371/journal.pone.0277953.].

Molecular modelling of the HCMV IL-10 protein isoforms and analysis of their interaction with the human IL-10 receptor.

The human cytomegalovirus (HCMV) UL111A gene encodes several homologs of the cellular interleukin 10 (cIL-10). Alternative splicing in the UL111A region produces two relatively well-characterized transcripts designated cmvIL-10 (isoform A) and LAcmvIL-10 (isoform B). The cmvIL-10 protein is the best characterized, both structurally and functionally, and has many immunosuppressive activities similar to cIL-10, while LAcmvIL-10 has more restricted biological activities. Alternative splicing also results in five less studied UL111A transcripts encoding additional proteins homologous to cIL-10 (isoforms C to G). These transcripts were identified during productive HCMV infection of MRC-5 cells with the high passage laboratory adapted AD169 strain, and the structure and properties of the corresponding proteins are largely unknown. Moreover, it is unclear whether these protein isoforms are able to bind the cellular IL-10 receptor and induce signalling. In the present study, we investigated the expression spectrum of UL111A transcripts in fully permissive MRC-5 cells and semi permissive U251 cells infected with the low passage HCMV strain TB40E. We identified a new spliced transcript (H) expressed during productive infection. Using computational methods, we carried out molecular modelling studies on the three-dimensional structures of the HCMV IL-10 proteins encoded by the transcripts detected in our work (cmvIL-10 (A), LAcmvIL-10 (B), E, F and H) and on their interaction with the human IL-10 receptor (IL-10R1). The modelling predicts clear differences between the isoform structures. Furthermore, the in silico simulations (molecular dynamics simulation and normal-mode analyses) allowed us to evaluate regions that contain potential receptor binding sites in each isoform. The analyses demonstrate that the complexes between the isoforms and IL-10R1 present different types of molecular interactions and consequently different affinities and stabilities. The knowledge about structure and expression of specific viral IL-10 isoforms has implications for understanding of their properties and role in HCMV immune evasion and pathogenesis.

Wastewater-based epidemiology: A Brazilian SARS-COV-2 surveillance experience.

Since 2020, developed countries have rapidly shared both publicly and academically relevant wastewater surveillance information. Data on SARS-CoV-2 circulation is pivotal for guiding public health policies and improving the COVID-19 pandemic response. Conversely, low- and middle-income countries, such as Latin America and the Caribbean, showed timid activities in the Wastewater-Based Epidemiology (WBE) context. In these countries, isolated groups perform viral wastewater monitoring, and the data are unevenly shared or accessible to health agencies and the scientific community. This manuscript aims to highlight the relevance of a multiparty effort involving research, public health, and governmental agencies to support usage of WBE methodology to its full potential during the COVID-19 pandemic as part of a joint One Health surveillance approach. Thus, in this study, we explored the results obtained from wastewater surveillance in different regions of Brazil as a part of the COVID-19 Wastewater Monitoring Network ANA (National Water Agency), MCTI (Ministry of Science, Technology, and Innovations) and MS (Ministry of Health). Over the epidemiological weeks of 2021 and early 2022, viral RNA concentrations in wastewater followed epidemiological trends and variations. The highest viral loads in wastewater samples were detected during the second Brazilian wave of COVID-19. Corroborating international reports, our experience demonstrated usefulness of the WBE approach in viral surveillance. Wastewater surveillance allows hotspot identification, and therefore, early public health interventions. In addition, this methodology allows tracking of asymptomatic and oligosymptomatic individuals, who are generally underreported, especially in emerging countries with limited clinical testing capacity. Therefore, WBE undoubtedly contributes to improving public health responses in the context of this pandemic, as well as other sanitary emergencies.