Hyaluronic acid is a negative regulator of mucosal fibroblast-mediated enhancement of HIV infection

Autor: Martin R Jakobsen, Warner C. Greene, Guorui Xie, Anders Laustsen, Jason Neidleman, Satish K. Pillai, Johanne H Egedal, Thomas A. Packard, Nadia R. Roan, Konstantinos Georgiou
Rok vydání: 2021
Předmět:
0301 basic medicine
CD4-Positive T-Lymphocytes
Human immunodeficiency virus (HIV)
HIV Infections
medicine.disease_cause
Medical and Health Sciences
Extracellular matrix
ACTIVATION
chemistry.chemical_compound
Foreskin
0302 clinical medicine
Hyaluronic acid
Immunology and Allergy
2.1 Biological and endogenous factors
Hyaluronic Acid
Aetiology
RISK
DEATH
IMMUNODEFICIENCY-VIRUS TYPE-1
Biological Sciences
Extracellular Matrix
RECEPTORS
medicine.anatomical_structure
Infectious Diseases
Gene Knockdown Techniques
Host-Pathogen Interactions
HIV/AIDS
Disease Susceptibility
medicine.symptom
Infection
GENITAL INFLAMMATION
Sexual transmission
ICAM-1
TRANSMISSION
Immunology
Inflammation
Biology
Article
Microbiology
03 medical and health sciences
CIAP2
Clinical Research
medicine
Humans
Fibroblast
Gene
Mucous Membrane
ACQUISITION
Fibroblasts
030104 developmental biology
chemistry
Gene Expression Regulation
HIV-1
Hyaluronan Synthases
030217 neurology & neurosurgery
Biomarkers
Zdroj: Mucosal immunology, vol 14, iss 5
Egedal, J H, Xie, G, Packard, T A, Laustsen, A, Neidleman, J, Georgiou, K, Pillai, S K, Greene, W C, Jakobsen, M R & Roan, N R 2021, ' Hyaluronic acid is a negative regulator of mucosal fibroblast-mediated enhancement of HIV infection ', Mucosal Immunology, vol. 14, no. 5, pp. 1203-1213 . https://doi.org/10.1038/s41385-021-00409-3
Mucosal Immunology
DOI: 10.1038/s41385-021-00409-3
Popis: The majority of HIV infections are established through the genital or rectal mucosa. Fibroblasts are abundant in these tissues, and although not susceptible to infection, can potently enhance HIV infection of CD4+ T cells. Hyaluronic acid (HA) is a major component of the extracellular matrix of fibroblasts, and its levels are influenced by the inflammatory state of the tissue. Since inflammation is known to facilitate HIV sexual transmission, we investigated the role of HA in genital mucosal fibroblast-mediated enhancement of HIV infection. Depletion of HA by CRISPR-Cas9 in primary foreskin fibroblasts augmented the ability of the fibroblasts to increase HIV infection of CD4+ T cells. This amplified enhancement required direct contact between the fibroblasts and CD4+ T cells, and could be attributed to both increased rates of trans-infection and the increased ability of HA-deficient fibroblasts to push CD4+ T cells into a state of higher permissivity to infection. This HIV-permissive state was characterized by differential expression of genes associated with regulation of cell metabolism and death. Our results suggest that conditions resulting in diminished cell-surface HA on fibroblasts, such as genital inflammation, can promote HIV transmission by conditioning CD4+ T cells toward a state more vulnerable to infection by HIV.
Databáze: OpenAIRE
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