HIV-2 interaction with cell coreceptors: amino acids within the V1/V2 region of viral envelope are determinant for CCR8, CCR5 and CXCR4 usage

© 2014 Santos-Costa et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Human immunodeficiency virus 1 and 2 (HIV-1 and HIV-2) use cellular receptors in distinct ways. Besides a more promiscuous usage of coreceptors by HIV-2 and a more frequent detection of CD4-independent HIV-2 isolates, we have previously identified two HIV-2 isolates (HIV-2MIC97 and HIV-2MJC97) that do not use the two major HIV coreceptors: CCR5 and CXCR4. All these features suggest that in HIV-2 the Env glycoprotein subunits may have a different structural organization enabling distinct - although probably less efficient - interactions with cellular receptors. Results: By infectivity assays using GHOST cell line expressing CD4 and CCR8 and blocking experiments using CCR8-specific ligand, I-309, we show that efficient replication of HIV-2MIC97 and HIV-2MJC97 requires the presence of CCR8 at plasma cell membrane. Additionally, we disclosed the determinants of chemokine receptor usage at the molecular level, and deciphered the amino acids involved in the usage of CCR8 (R8 phenotype) and in the switch from CCR8 to CCR5 or to CCR5/CXCR4 usage (R5 or R5X4 phenotype). The data obtained from site-directed mutagenesis clearly indicates that the main genetic determinants of coreceptor tropism are located within the V1/V2 region of Env surface glycoprotein of these two viruses. Conclusions: We conclude that a viral population able to use CCR8 and unable to infect CCR5 or CXCR4-positive cells, may exist in some HIV-2 infected individuals during an undefined time period, in the course of the asymptomatic stage of infection. This suggests that in vivo alternate molecules might contribute to HIV infection of natural target cells, at least under certain circumstances. Furthermore we provide direct and unequivocal evidence that the usage of CCR8 and the switch from R8 to R5 or R5X4 phenotype is determined by amino acids located in the base and tip of V1 and V2 loops of HIV-2 Env surface glycoprotein.This work was supported by grants from: Fundação para a Ciência e Tecnologia (FCT; PPCDT/SAU-IMI/55726/2004); Fundação para a Ciência e Tecnologia and Ministério da Saúde de Portugal (VIH/SAU/0006/2011); and from Gilead Sciences Portugal (Programa Gilead Génese).info:eu-repo/semantics/publishedVersio

Using graph theory to analyze biological networks

Understanding complex systems often requires a bottom-up analysis towards a systems biology approach. The need to investigate a system, not only as individual components but as a whole, emerges. This can be done by examining the elementary constituents individually and then how these are connected. The myriad components of a system and their interactions are best characterized as networks and they are mainly represented as graphs where thousands of nodes are connected with thousands of vertices. In this article we demonstrate approaches, models and methods from the graph theory universe and we discuss ways in which they can be used to reveal hidden properties and features of a network. This network profiling combined with knowledge extraction will help us to better understand the biological significance of the system

DEVELOPMENT OF REGULATION DISORDERS INTO SPECIFIC PSYCHOPATHOLOGY

Underlying deficits in self-regulation and sensory processing are seen in children with regulation disorders (RD) and might lead to emotional and behavioral problems as the child develops. However, little is known about the specific developmental course of RD. This follow-up study was conducted to investigate the development of a clinical sample of RD children, diagnosed by means of the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood, Revised (DC:0-3R; ZERO TO THREE, 1994), toward specific psychopathology 4 to 10 years later based on parent- and teacher-reports on the Child Behavior Checklist (T.M. Achenbach & L.A. Rescorla, 2007). Parental reports showed that 39 to 69% of children with RD had internalizing, externalizing, and total problems above borderline cutoffs, as compared to norm group data (16%). In addition, higher rates of affective, anxiety, attention deficit/hyperactivity, oppositional defiant, and conduct problems were reported. Analyses between RD subtypes showed significant differences on future attention problems and rule-breaking behavior, wherein less favorable results were found for the Hypersensitive subtype Type A (fearful/cautious) in comparison to the sensory stimulation-seeking/impulsive subtype. The current results indicate persistence of emotional and behavioral problems into middle childhood and adolescence in children with preschool RD diagnoses. More attention should be paid to differentiation of psychopathology in these children since developmental outcomes may differ between RD subtypes

Laser refractive surgery in corneal dystrophies

Twenty-eight case reports and case series published between 2000 and 2019 concerning laser refractive surgery in patients with corneal dystrophies, resulting in 173 eyes from 94 patients, were included in this systematic review. Best results were achieved in posterior corneal polymorphous and Cogan dystrophy. Unfavorable results were found in Avellino dystrophy and Fuchs endothelial corneal dystrophy (FECD). Photorefractive keratectomy was not indicated in Meesmann and Avellino dystrophy. Laser in situ keratomileusis was indicated in posterior polymorphous corneal dystrophy but not in FECD, Avellino, or Cogan dystrophy. Small-incision lenticule extraction and other dystrophies such as lattice, fleck, Lisch, or François did not achieve enough scientific evidence to report any recommendation