Effects on Intracellular Virus Replication

Aside from the inactivation of cell-free virus in vitro, ascorbate has been shown to inhibit the growth and expression of virus in laboratory cultures of infected cells. The first report of ascorbate-mediated inhibition of viral growth was made in cell cultures infected with rhino virus. Ascorbate, in concentrations nontoxic to host cells, interfered with progressive multicycle replication of rhino virus in cultures of WI-38 human fibroblasts (Schwerdt and Schwerdt, 1975). The authors did not determine the mechanism of the inhibitory effect, although they ruled out the involvement of interferon. 

Further investigations of ascorbate inhibition of virus replication have been carried out using retroviruses as models. Bissell et al. (1980), working with the avian retrovirus of chickens, found that while cell-free virus was resistant to ascorbate inactivation upon short-term treatment in vitro, exposure of virus-infected cultures to the vitamin resulted in reduction of virus replication and lowered infec-tivity of newly replicated virus. A subsequent study found that ascorbate interfered with the replication and cell-transforming potential of Rous sarcoma virus by stabilizing the differentiated state of chicken cells (Schwarz, 1991). In a lymphocytic cell line latently infected with human T-cell leukemia virus (HTLV-1), ascorbate was shown to interfere with virus production triggered by chemical inducers added to the culture medium (Blakeslee et al., 1985). 

In more recent studies, the effect of ascorbate was investigated in latently infected cell lines that had been stimulated with tumor promoter or inflammatory cytokine to trigger virus production (Harakeh and Jariwalla, 1994, and unpublished data). Pretreatment of cells with 100-300 jLg/ml ascorbate followed by cell stimulation with phorbol ester (PMA) or cytokine (TNF-a) resulted in dose-dependent suppression of virus activation. Unlike N-acetyl cysteine (NAC), which suppressed cytokine-stimulated HIV expression through inhibition of transcriptional activation by NF-kB, ascorbate seemed to have no effect on the activity of this transcription factor. AZT, a known inhibitor of de novo infection, had no effect on virus production in either unstimulated chronically infected cells or in stimulated latently infected cells (Harakeh and Jariwalla, 1994). 

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