CCR5 and Biological Complexity: The Need for Data Integration and Educational Materials to Address Genetic/Biological Reductionism at the Interface of Ethical, Legal, and Social Implications

Abstract

In the age of genomics, public understanding of complex scientific knowledge is critical. To combat reductionistic views, it is necessary to generate and organize educational material and data that keep pace with advances in genomics. The view that CCR5 is solely the receptor for HIV gave rise to demand to remove the gene in patients to create host HIV resistance, underestimating the broader roles and complex genetic inheritance of CCR5. A program aimed at providing research projects to undergraduates, known as CODE, has been expanded to build educational material for genes such as CCR5 in a rapid approach, exposing students and trainees to large bioinformatics databases and previous experiments for broader data to challenge commitment to biological reductionism. Our students organize expression databases, query environmental responses, assess genetic factors, generate protein models/dynamics, and profile evolutionary insights into a protein such as CCR5. The knowledgebase generated in the initiative opens the door for public educational information and tools (molecular videos, 3D printed models, and handouts), classroom materials, and strategy for future genetic ideas that can be distributed in formal, semiformal, and informal educational environments. This work highlights that many factors are missing from the reductionist view of CCR5, including the role of missense variants or expression of CCR5 with neurological phenotypes and the role of CCR5 and the delta32 variant in complex critical care patients with sepsis. When connected to genomic stories in the news, these tools offer critically needed Ethical, Legal, and Social Implication (ELSI) education to combat biological reductionism.

The complex, dynamic SpliceOme of the small GTPase transcripts altered by technique, sex, genetics, tissue specificity, and RNA base editing

“…As blood is an easily collectible material through the use of PAXgene tubes, and one in which our group has built extensive bioinformatics analyses ( Prokop et al, 2020 ; Prokop et al, 2021 ; Bauss et al, 2021 ; Gupta et al, 2021 ), we curated small GTPase expression within 16,243 samples from 116 BioProjects for “Blood PAXgene.” Samples from this database represent healthy individuals and patients with various pathologies, capturing all known human samples from a single collection tube type ( https://doi.org/10.6084/m9.figshare.21381900.v1 tabs SRA PAXgene Blood BioProjects, SRA PAXgene Blood Samples, Figure 4 ). This represents an array of isolation and sequencing strategies, including polyA RNAseq, total (ribosomal reduction ± globin reduction), or small RNA isolations such as miRNA.…”

Targeting C–C Chemokine Receptor 5: Key to Opening the Neurorehabilitation Window After Ischemic Stroke

“…Furthermore, the enhancement of neuronal excitability after inhibition of CCR5 increases neuronal death in the acute phase; therefore, CCR5-targeted treatment at a specified time in the late subacute phase may be more beneficial for ischemic stroke ( Clarkson et al, 2011 ; Joy and Carmichael, 2021 ). Although it plays multiple roles represented by immunology in the CNS, inhibition of CCR5 during pathological injury does not reduce immune microglial migration, which notes the loss of CCR5 may be compensated by increased expression of CCR3 and CCR2 ( Bauss et al, 2021 ). Therefore, due to the complexity and interactions of the chemokine receptor family, the benefits of CCR5-targeted therapy after stroke require further investigation and confirmation.…”

CCR5 promoter region polymorphisms in systemic lupus erythematosus

“…Moreover, if the CCR5Δ32 is, on one hand, a risk factor for severe West Nile virus infection (Glass et al., 2006), on the other hand, in the Brazilian population the CCR5Δ32 is a protective factor for pre‐eclampsia (Kaminski et al., 2019), rheumatoid arthritis (Toson et al., 2017) and multiple sclerosis (Troncoso et al., 2018) as the CCR5Δ32 may downregulate inflammatory responses in such diseases. These multiple findings indicate the pleiotropic characteristic of CCR5 and the biological complexity of CCR5 protein (Bauss et al., 2021) but, at the same time, open the way for new CCR5‐related therapies.…”

“…Indeed, CCR5 protein and CCR5 gene variants have been shown to be involved in multiple conditions. For example, CCR5 acts on neuroactivity and memory (Bauss et al., 2021; Shen et al., 2022). Moreover, if the CCR5Δ32 is, on one hand, a risk factor for severe West Nile virus infection (Glass et al., 2006), on the other hand, in the Brazilian population the CCR5Δ32 is a protective factor for pre‐eclampsia (Kaminski et al., 2019), rheumatoid arthritis (Toson et al., 2017) and multiple sclerosis (Troncoso et al., 2018) as the CCR5Δ32 may downregulate inflammatory responses in such diseases.…”