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Human adipose cells express CD4, CXCR4, and CCR5 [corrected] receptors: a new target cell type for the
Uriel Hazan1, Ignacio A Romero, Raffaella Cancello
1CNRS UPR 0415 and, INSERM U380, Institut Cochin de Génétique Moléculaire, 75014 Paris, France.
Abstract:
The concept that adipocytes belong to an essential endocrine system with some characteristics of immune cells has recently emerged. The aim of this paper is to present evidence of the expression of CD4, CXCR4, and CCR5 receptors by human adipocytes and to test whether adipose cells support HIV entry. Primary human preadipocytes were cultured and differentiated in vitro. Expression of the three receptors on preadipocytes and adipocytes was demonstrated by reverse transcriptase-polymerase chain reaction, immunocytochemical, and immunohistochemical analysis. Infection of adipose cells to HIV-1 was then investigated. The measurement of the viral p24 antigen in preadipocyte culture medium showed an increase of p24 levels between 24 and 72 h postexposure and then a progressive decrease to reach a low level at 10-15 days. Ten days after the infection test, supernatant of preadipocytes contained infectious particles able to infect the susceptible T-CD4 CEM cell line. The expression of viral proteins by adipocytes was confirmed using a fusion test. The presence of viral DNA was exhibited by gag-specific polymerase chain reaction, supporting the hypothesis of HIV-1 X4- and R5-virus entry in preadipocytes. Adipose cells represent the first cell type that does not belong to the immune system expressing all specific HIV receptors and may represent new HIV-1 target cells.
Insights
Human fat cells (adipocytes) express receptors enabling HIV entry, suggesting they are a novel target for the virus. This finding expands our understanding of HIV infection beyond immune cells.
Area of Science:
- Immunology
- Cell Biology
- Endocrinology
Background:
- Adipocytes are increasingly recognized as having endocrine functions and immune-like characteristics.
- Previous research has not established adipocytes as a target for HIV infection.
Purpose of the Study:
- To investigate the expression of CD4, CXCR4, and CCR5 receptors on human adipocytes.
- To determine if human adipocytes support HIV entry and replication.
Main Methods:
- Primary human preadipocytes were differentiated in vitro.
- Receptor expression was analyzed using RT-PCR, immunocytochemistry, and immunohistochemistry.
- HIV-1 infection was assessed by measuring viral p24 antigen, infectious particle release, viral protein expression, and viral DNA presence.
Main Results:
- Human adipocytes and preadipocytes express CD4, CXCR4, and CCR5 receptors.
- Adipocytes were successfully infected with HIV-1, showing viral replication and release of infectious virions.
- Viral DNA and proteins were detected in infected adipocytes, confirming HIV entry and replication.
Conclusions:
- Adipocytes are the first non-immune cells identified to express all specific HIV receptors (CD4, CXCR4, CCR5).
- Human adipocytes represent a novel target cell type for HIV-1 infection.
- These findings suggest a potential role for adipose tissue in HIV pathogenesis and viral reservoirs.
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