Murabutide inhibits HIV replication in macrophages and dendritic cells
The synthetic immunomodulator Murabutide inhibits HIV replication in macrophages and dendritic cells through multiple mechanisms, according to researchers in France, who suggest that the potential of Murabutide as an adjuvant to antiretroviral therapy should be explored.
Macrophages and dendritic cells are CD4-expressing antigen-presenting cells that are important in establishing and maintaining HIV infection, Dr George M. Bahr of the Institut Pasteur de Lille and colleagues explain. They therefore examined the ability of Murabutide to suppress HIV replication in monocyte-derived versions of these cell types.
As they report in the September issue of the Journal of Virology, Murabutide was highly efficient at suppressing viral replication in both cell types without affecting viral entry, reverse transcriptase activity, or early cytoplasmic proviral DNA formation.
The authors also observed that Murabutide inhibited replication by reducing proviral DNA integration and viral messenger RNA transcription, which did not occur by inhibition of cellular DNA synthesis or activation of p38 mitogen-activated protein kinase.
In addition, Dr Bahr and colleagues found that Murabutide reduced cellular expression of CD4 and CCR5 and led to secretion of high levels of beta-chemokines. However, the beta-chemokines were not necessary for the drug to inhibit HIV-1 replication.
“Our findings demonstrate a potent HIV-suppressive activity of a safe synthetic immunomodulator and a profile of antigen-presenting cell activation that is associated with protective responses against infection,” they conclude.
The authors note that Murabutide also inhibits HIV replication in T cells and in the humanized severe combined immunodeficient mouse model. “Confirmation of these results and the good clinical tolerance of Murabutide by HIV-infected patients may rapidly contribute to the serious evaluation of a new immunotherapeutic approach, as an adjunct to antiretroviral agents, in the management of HIV disease,” the researchers write.
J Virol 2000;74:7794-7802.
Source: Reuters Health