Productive in vitro infection of human umbilical vein endothelial cells and three colon carcinoma cell lines with HIV‐1

Abstract

Summary The objective of this study was to assess the ability of HIV‐1 to establish an in vitro infection of primary human umbilical vein endothelial cells (HUVEC). The HUVEC and colon carcinoma cell lines were inoculated with different isolates of HIV‐1 (HIV‐1SF2, HIV‐1McK and HIV‐1LAI) and productive viral infection was assessed by both the detection of p24 core antigen in the culture supernatants and the presence of specific spliced HIV mRNA. The infection which was detected in the inoculated HUVEC and all the colon carcinoma cell lines could not be blocked using an antibody targeted against the CD4 receptor. Furthermore, the HIV‐inoculated HUVEC secreted elevated levels of IL‐6 and this increase was found to be proportional to the size of the viral inoculum. No changes in the production of IL‐lβ, TNF‐α, IFN‐α and IFN‐γ were detected following HIV infection. The colon carcinoma cells, however, did not secrete increased levels of these cytokines following HIV‐1 inoculation. These results confirm that non‐CD4 expressing cells, such as endothelial cells and certain colon epithelial cells, serve as targets and reservoirs for HIV. Moreover, the production of IL‐6 by HIV‐infected endothelial cells may be a contributing factor to the aberrant immunoregulation associated with HIV infection in vivo.

Platelet activating factor produced in vitro by Kaposi's sarcoma cells induces and sustains in vivo angiogenesis.

“…The cultures were named AIDS-IST-KS3, AIDS-IST-KS4, IST-KS8, and AIDS-IST-KSII, respectively (abbreviated to KS3, KS4, KS8, and KS1 1). Cells had the elongated morphological aspect typical of spindle-shaped KS cells (20)(21)(22)25); immunohistochemical characterization showed positivity for vimentin, collagen I, laminin, smooth muscle actin, and desmin, but not for CD45, von Willebrand factor, and EN4 antigen, in agreement with previous reports (20,25,58,59) and as already described (23). Cells were grown on plastic surface coated with gelatin in RPMI 1640 containing 20% FCS supplemented with amino acids and 0.5% Ultroser HY.…”

“…The introduction of routine cell culture of KS-derived spindle cells (20)(21)(22)(23) has made it possible to demonstrate that they produce and respond to various soluble mediators ( 19,(24)(25)(26)(27)(28)(29)(30). Oncostatin M (27, 28), IL-6 (25), IL-1 (24), and GM-CSF (30), as well as Tat protein (29), stimulate KS cell growth in vitro.…”

Gp120 activates children's brain endothelial cells via CD4

“…CD4 has been reported to be present on microvascular endothelial cells of the human hepatic sinusoid (Nagura et al, 1986). In contrast, CD4 was found to be absent on portal liver endothelium and macrovascular HUVEC (Lafon et al, 1992;Conaldi et al, 1995;Corbeil et al, 1995). Other investigators also failed to demonstrate CD4 on brain endothelial cells derived from adults (Moses et al, 1993;Poland et al, 1995).…”

Chemokine Receptors in Human Endothelial Cells

“…Apart from this, CXCR4 is a co-receptor for the infection of T-lymphotropic strains of HIV-1 in CD4-positive susceptible cells (26). It is noteworthy that many cell lines that do not express CD4, including EC, are also susceptible to infection with various strains of HIV (32,53) by a CD4-independent mechanism. Although the chemokine receptor preferences of these HIV-1 strains have not been studied yet, it may involve the use of CXCR4 as their primary receptor.…”