Productive HIV-1 infection of human vascular endothelial cells requires cell proliferation and is stimulated by combined treatment with interleukin-1β plus tumor necrosis factor-α

P. G. Conaldi, C. Serra, A. Dolei, F. Basolo, V. Falcone, G. Mariani, P. Speziale, A. Toniolo

Research output: Contribution to journalArticle

Abstract

Vascular endothelial cells (EC) play a key role in viral tropism in vivo. Since conflicting reports have been published on the capability of HIV to infect EC in vitro, we analyzed some factors potentially capable of influencing the susceptibility of human umbilical vein endothelial cells (HUVEC) to HIV-1. Both primary cultures and differentiated immortalized HUVEC lines were used. HUVEC were negative for the expression of CD4, but weakly CD26- and galactosylceramide-positive. Although binding of HIV to EC was substantial, the virus was apparently incapable of replicating in nonproliferating cultures. In resting cultures, the content of cell-associated HIV disappeared 4-6 days after infection without production of p24 and infectious progency. In contrast, infection of proliferating EC cultures led to the transient release of p24 and infectious virus (102.5-103.5 SFU/ml) peaking 2-6 days postinfection. Antibody neutralization of cytokines that may be produced by EC (IL1, IL6, IL8, TNF, IFN-β) failed to modify virus adsorption and replication, whereas treatment with IL1-β plus TNF-α stimulated both virus binding and virus release. As seen by gag polymerase chain reaction (PCR), the viral genome persisted up to 15 days in untreated EC cultures, but over 20 days in cultures exposed to IL1-β plus TNF-α. This study shows that: (a) CD4-negative HUVEC are capable of binding substantial amounts of HIV-1; (b) binding is enhanced by proinflammatory cytokines; (c) the establishment of productive infection is favored by cell proliferation; and (d) exposure to IL1-β plus TNF-α enhances virus replication.

Original languageEnglish
Pages (from-to)355-363
Number of pages9
JournalJournal of Medical Virology
Volume47
Issue number4
DOIs
Publication statusPublished - 1995

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Keywords

  • Cytokines
  • Endothelium
  • HIV adsorption
  • HIV replication

ASJC Scopus subject areas

  • Virology

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