Imbalance in production of cytokines by bone marrow stromal cells following cytomegalovirus infection.

The effect of cytomegalovirus (CMV) infection on the production of growth factors and negative regulators in unstimulated or lipopolysaccharide-stimulated human bone marrow stromal cells was assessed. After 5 days, the constitutive and lipopolysaccharide-stimulated production of growth factors was significantly decreased in CMV-infected compared with uninfected stromal cells. This decrease was noted as early as 72 h after infection and appeared to be strictly related to viral replication. On the other hand, the production of inhibitory factors was increased after CMV infection, and this increased release was detectable as early as 24 h after infection. No modulation in the production of interleukin-10 was observed after CMV infection. These data suggest that CMV disturbs the balanced cytokine network, which controls proliferation and differentiation of hematopoietic progenitors. CMV-induced myelosuppression results from this lack of production of growth factors and excess production of inhibitory factors.

Synthesis of novel 6-substituted acyclouridine derivatives and their anti-HIV-1 activity.

To improve the anti-HIV activity of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), a variety of its analogues were synthesized. Introduction of SR group to the C-6 position was carried out based on LDA lithiation followed by the reaction of aryl- or alkyl disulfide. An addition-elimination reaction of a 6-phenylsulfinyl derivative was used for synthesizing the analogues having OR or NHR group at the C-6 position. The C-5 modified derivatives were synthesized mainly based on LTMP lithiation of a 6-phenylthio derivative. Modification at the 2- or 4-position was also carried out. Some compounds prepared in the present study showed higher activity than HEPT.