Productive HIV-1 infection of human vascular endothelial cells requires cell proliferation and is stimulated by combined treatment with interleukin-1 beta plus tumor necrosis factor-alpha.
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 (10(2.5)-10(3.5) SFU/ml) peaking 2-6 days postinfection. Antibody neutralization of cytokines that may be produced by EC (IL1, IL6, IL8, TNF, IFN-beta) failed to modify virus adsorption and replication, whereas treatment with IL1-beta plus TNF-alpha 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-beta plus TNF-alpha. 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-beta plus TNF-alpha enhances virus replication.
Conaldi
P G
PG
Institute of Medicine and Public Health, University of Pavia, Italy.
Serra
C
C
Dolei
A
A
Basolo
F
F
Falcone
V
V
Mariani
G
G
Speziale
P
P
Toniolo
A
A
D015704:CD4 Antigens / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D013539:Simian virus 40; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014470:Umbilical Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014779:Virus Replication
D015704:CD4 Antigens; D003470:Culture Media; D016207:Cytokines; D016655:HIV Core Protein p24; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha