Epstein-Barr virus promotes human monocyte survival and maturation through a paracrine induction of IFN-alpha.
The role of monocytes and macrophages during EBV infection is not clear. The interaction of EBV with human monocytes was investigated in terms of cell survival and morphological and phenotypic changes to gain a better understanding of the role of these cells during EBV infection. We show that EBV infection of PBMCs rescues monocytes from undergoing spontaneous apoptosis and dramatically enhances their survival. Results obtained with heat-inactivated virus, neutralizing anti-EBV mAb 72A1 and recombinant gp350, suggest that enhancement of viability by EBV requires both infectious virus and interaction between gp350 and its receptor. IFN-alpha either secreted within 24 h from PBMCs upon infection with EBV or exogenously added to unstimulated monocytes inhibited spontaneous apoptosis, indicating that induction of IFN-alpha is an early important survival signal responsible for the delay in the apoptosis of monocytes. EBV infection also induced acute maturation of monocytes to macrophages with morphological and phenotypic characteristics of potent APCs. Monocytes exposed to EBV became larger in size with increased granularity and expressed considerably higher levels of membrane HLA classes I and II, ICAM-1, CD80, CD86, and CD40 compared with uninfected cultures. These observations provide the first immunoregulatory links among EBV, IFN-alpha, and monocyte survival and maturation and importantly raise the possibility that these cells may serve as a vehicle for the dissemination of the virus as well as being active participants in eliciting anti-EBV T cell responses during acute infection.
Salek-Ardakani
Shahram
S
Department of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Withington, Manchester, UK. ssalek@liai.org
Lyons
Stephen A
SA
Arrand
John R
JR
D017209:Apoptosis; D002470:Cell Survival; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D009000:Monocytes / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000502:physiology
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016898:Interferon-alpha; D014763:Viral Matrix Proteins