Human foamy virus (HFV) is a human retrovirus that has not been clearly associated with human disease. In this study, we tested the capacity of nucleoside derivatives to inhibit the infectivity and cytopathic effect of HFV in T-lymphoblastoid cells in vitro. H9 cells showed a dramatic cytopathic effect 3 weeks after exposure to HFV. At this time, viral infection was demonstrated by detection of viral antigens by immunofluorescence staining, release of reverse transcriptase activity (RT) in the supernatant, detection of typical viral particles by electron microscopy, and presence of proviral DNA by Southern blot analysis. H9 cells were pretreated with dideoxycytidine (ddC), dideoxyinosine (ddI), or azidothymidine (AZT) at various concentrations before HFV infection. ddC could not completely suppress viral replication at low concentrations, and inhibited cell proliferation at higher concentrations. ddI partially inhibited the formation of giant cells at 10 microM, with 95% inhibition of RT in the supernatant. AZT induced a complete inhibition of cytopathic effect at concentrations> or = 1 microM, with more than 95% inhibition of RT in the supernatant. Moreover, the synthesis of proviral DNA was completely suppressed by 10 microM AZT. These results show that AZT and ddI can inhibit HFV replication in vitro.
Human foamy virus (HFV) belongs to the spumaretrovirus group of the Retroviridae taxonomic family. Attempts to associate HFV or other foamy viruses to a specific pathology still remain unsuccessful. However, viral gene expression as well as tissue-specific tropism in an in vivo context remain poorly analyzed. To address this issue, we have infected domestic rabbits with a single dose of HFV and followed them at the biological and molecular levels for 5 years. No apparent pathology was detectable in the infected animals which have developed a strong immunological response against major viral proteins. We found that HFV provirus in blood cells and several organs persisted predominantly in its defective form, delta HFV, suggesting that in vivo viral persistence could be related to homologous interference as was recently shown in vitro. This animal model might be useful for studying the in vivo targets of HFV and should also be convenient for testing therapeutic effects of antiretroviral drugs.
Figure 1 Selected sections of MRI of the brain. MRI showed diffuse increased signal on T2 FLAIR images involving lateral thalamic, midbrain, and cerebellar areas, with cerebral edema present.
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