Anti-

Both Toxoplasma gondii and Plasmodium are Apicomplexan protozoa that share common metabolic pathways and potential drug targets. The objective of this study was to examine the anti- Toxoplasma activity of nine West African plants with known activity against P. falciparum. The extracts were obtained from parts of plant commonly used, by most traditional healers, in the form of infusion or as water decoction. The in vitro activity of plant extracts on T. gondii was assessed on MRC5 tissue cultures and was quantified by enzyme-linked immunoassay. Aqueous extracts from Vernonia colorata were found to be inhibitory for Toxoplasma growth at concentrations > 10 mg/L, with an IC50 of 16.3 mg/L. A ten-fold gain in activity was obtained when organic solvents such as dichloromethane, acetone or ethanol were used to extract V. colorata's active principles. These extracts were inhibitory at concentrations as low as 1 mg/L, with IC50 of 1.7, 2.6 and 2.9 mg/L for dichloromethane, acetone and ethanol extracts respectively. These results indicate a promising source of new anti-Toxoplasma drugs from V. colorata and African medicinal plants

Anti-Toxoplasma activity of vegetal extracts used in West African traditional medicine

Both Toxoplasma gondii and Plasmodium are Apicomplexan protozoa that share common metabolic pathways and potential drug targets. The objective of this study was to examine the anti- Toxoplasma activity of nine West African plants with known activity against P. falciparum. The extracts were obtained from parts of plant commonly used, by most traditional healers, in the form of infusion or as water decoction. The in vitro activity of plant extracts on T. gondii was assessed on MRC5 tissue cultures and was quantified by enzyme-linked immunoassay. Aqueous extracts from Vernonia colorata were found to be inhibitory for Toxoplasma growth at concentrations > 10 mg/L, with an IC50 of 16.3 mg/L. A ten-fold gain in activity was obtained when organic solvents such as dichloromethane, acetone or ethanol were used to extract V. colorata's active principles. These extracts were inhibitory at concentrations as low as 1 mg/L, with IC50 of 1.7, 2.6 and 2.9 mg/L for dichloromethane, acetone and ethanol extracts respectively. These results indicate a promising source of new anti-Toxoplasma drugs from V. colorata and African medicinal plants

Reactivation of a complex retrovirus is controlled by a molecular switch and is inhibited by a viral protein

Spumaviruses, commonly called foamy viruses (FV), are complex retroviruses that establish lifelong persistent infections without any accompanying pathologies. In tissue culture, cells can be either lytically or latently infected, depending on cell type. Regulation of FV replication is controlled by two promoters: the LTR and a second promoter within the env gene termed the internal promoter (IP). The IP directs expression of the transcriptional activator, Tas, and a second accessory protein, Bet, whose function has been elusive. In this study, we report that expression of exogenous Tas is sufficient to initiate a switch from latent to lytic replication. We also show that treatment with the phorbol ester phorbol 12-myristate 13-acetate (PMA) can lead to an increase in transcription from the IP, and that Bet protein expression abrogates this effect. Finally, we demonstrate that Bet expression severely limits the ability of PMA to activate transcription of latent FV genomes, and that replication of a Bet(-) virus is more easily activated than wild-type FV. Taken together, these data suggest that viral transcription is regulated by a sensitive switch, and that Bet functions as a negative regulator of basal IP activity

Cell-Type-Specific Regulation of the Two Foamy Virus Promoters

The foamy virus (FV) genome contains two promoters, the canonical long terminal repeat (LTR) promoter, containing three consensus AP-1 binding sites, and an internal promoter (IP) within the env gene. We investigated the regulation of the two promoters in lytic and persistent infections and found that in the presence of a constitutive source of the viral transactivator protein Tas, transactivation of the LTR promoter and that of the IP differ. In lytic infections, both the LTR promoter and the IP are efficiently transactivated by Tas, while in persistent infections, the IP is efficiently transactivated by Tas, but the LTR promoter is not. Analysis of proteins expressed from the LTR promoter and the IP during infection indicated that IP transcription is more robust than that of the LTR promoter in persistently infected cells, while the opposite is true for lytically infected cells. Coculture experiments also showed that LTR promoter transcription is greatest in cells which support lytic replication. Replacement of much of the LTR promoter with the IP leads to increased viral replication in persistent but not lytic infections. We also found that the induction of persistently infected cells with phorbol 12-myristate 13-acetate (PMA) greatly enhanced viral replication and transcription from the SFVcpz(hu) (new name for human FV) LTR promoter. However, mutation of three consensus AP-1 binding sites in the FV LTR promoter did not affect viral replication in lytically or persistently infected cells, nor did the same mutations affect LTR promoter transactivation by Tas in PMA-treated cells. Our data indicate that differential regulation of transcription is important in the outcome of FV infection but is unlikely to depend on AP-1

Historical Perspective of Foamy Virus Epidemiology and Infection

Foamy viruses (FV) are complex retroviruses which are widespread in many species. Despite being discovered over 40 years ago, FV are among the least well characterized retroviruses. The replication of these viruses is different in many interesting respects from that of all other retroviruses. Infection of natural hosts by FV leads to a lifelong persistent infection, without any evidence of pathology. A large number of studies have looked at the prevalence of primate foamy viruses in the human population. Many of these studies have suggested that FV infections are prevalent in some human populations and are associated with specific diseases. More recent data, using more rigorous criteria for the presence of viruses, have not confirmed these studies. Thus, while FV are ubiquitous in all nonhuman primates, they are only acquired as rare zoonotic infections in humans. In this communication, we briefly discuss the current status of FV research and review the history of FV epidemiology, as well as the lack of pathogenicity in natural, experimental, and zoonotic infections