Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
Abstract
HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complement-opsonized virus. The mucosal transcriptional response at 24h revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96h in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, i.e. Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, e.g. expression of regulatory factors, especially when the virions were opsonized with complement factors. Our findings suggest that HIV-opsonization alters the activation and signaling pathways in the colorectal mucosa, which promotes viral establishment by creating an environment that stimulates mucosal T cell activation and inflammatory Th cells.
Data availability
Sequencing data (RNA seq) have been deposited in GEO, under the accession number GSE149749.
-
Colorectal mucosa exposed to free and complement opsonized HIVNCBI Gene Expression Omnibus, GSE149749.
Article and author information
Author details
Funding
Vetenskapsrådet (Project grant)
- Marie Larsson
Läkare emot AIDS (Project grant)
- Marie Larsson
Forsknings-ALF (Project grant)
- Marie Larsson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Nicola L Harris, Monash University, Australia
Ethics
Human subjects: This study was approved by the Linköping University Ethical Review Board (Ethical permit EPN M206-06). The subjects were informed about the study at the clinic and verbal consents were obtained and documented from all participating subjects, as approved by the Linköping University Ethical Review Board. The study included both male and female adult subjects who were 18 years or older.
Version history
- Received: April 15, 2020
- Accepted: September 2, 2020
- Accepted Manuscript published: September 2, 2020 (version 1)
- Version of Record published: September 15, 2020 (version 2)
Copyright
© 2020, Bhattacharya et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,128
- views
-
- 133
- downloads
-
- 5
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Microbiology and Infectious Disease
- Structural Biology and Molecular Biophysics
Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we examine the impact of mutations across the spectrum of viable amino acid sequences on the biophysical phenotypes of the highly expressed and multifunctional nucleocapsid protein. We find variation in the physicochemical parameters of its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur in related coronaviruses. In biophysical experiments with several N-protein species carrying mutations associated with major variants, we find that point mutations in the IDRs can have nonlocal impact and modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, and liquid-liquid phase separation. In the Omicron variant, distant mutations in different IDRs have compensatory effects in shifting a delicate balance of interactions controlling protein assembly properties, and include the creation of a new protein-protein interaction interface in the N-terminal IDR through the defining P13L mutation. A picture emerges where genetic diversity is accompanied by significant variation in biophysical characteristics of functional N-protein species, in particular in the IDRs.
-
- Microbiology and Infectious Disease
- Structural Biology and Molecular Biophysics
A new study reveals how naturally occurring mutations affect the biophysical properties of nucleocapsid proteins in SARS-CoV-2.