Novel Protein In St. John's Wort Found To Suppress HIV-1 Gene Expression

Their findings, “p27^SJ, a novel protein in St. John’s wort, that suppresses expression of HIV-1 genome,” will be published online in the Oct. 27 issue of Gene Therapy (http://www.nature.com/gt).

Kamel Khalili, Ph.D., director of CNV (http://www.temple.edu/cnvcb), professor and acting chair of Temple’s department of neuroscience, and the study’s lead author, said the researchers were originally examining plant extracts from St. John’s wort cultured in the laboratory to see if they had any effect on cell growth or the behavior of brain cells in vitro.

“During the course of that study, we also looked to see whether these plant extracts that we had isolated from the callus culture had any anti-viral activity,” said Khalili. “We soon discovered that the plant extract inhibited HIV-1 gene expression and replication in infected cells.”

Next, the team sought to isolate the protein from the plant extract responsible for the observed anti-viral activity. After identifying the protein, the group cloned the gene, which they realized was a novel protein and named p27^SJ.

“It has unique characteristics,” said Khalili. “Remember, it is a plant protein, and so far, to my knowledge, there is no similar protein to that in mammalian cells.”

After cloning the gene, the researchers then were able to identify the molecular mechanism by which the protein is able to suppress HIV-1 gene expression and replication, according to Khalili.

It is the expression of the viral gene and the replication of the viral genome that leads to the development of AIDS in HIV-infected individuals.

“Our studies indicate that p27^SJ has the capacity to inhibit expression of the HIV-1 gene by interacting with both cellular proteins and viral proteins,” said Khalili. “Since HIV-1 gene expression relies heavily on these factors, p27^SJ can block viral replication by interfering with the proteins recruited by HIV-1 to increase viral gene expression.”

Although St. John’s wort is a popular herb that can be purchased as a dietary supplement over the counter in health food stores, neighborhood pharmacies and supermarkets, the Temple researchers did not use the supplement as a source for St. John’s wort during the study. As a supplement, St John’s wort is often taken as an anti-depressant, although the Food and Drug Administration has not approved it as such, so manufacturers cannot advertise it as a depression treatment nor can doctors prescribe it.

Khalili strongly emphasized that the researchers do not know if the p27^SJ protein they discovered is present in the St. John’s wort preparations sold as a dietary supplement, and therefore, those tablets should not be considered as a treatment for patients infected with HIV-1.

“We don’t know yet how we have to deliver the protein to cells infected with HIV-1,” he said. “Even if the protein were present in the tablets, we don’t know how much might be present and whether the protein would be effective when ingested.”

The study, which was partially funded through grants from the National Institutes of Health, was done in collaboration with Yerevan State University in Armenia. Khalili’s co-investigators included Nune Darbinian-Sarkissian, Armine Darbinyan, Jessica Otte, Sujatha Radhakrishnan, Bassel E. Sawaya, Alla Arzumanyan, Galina Chipitsyna, Jay Rappaport and Shoreh Amini from Temple’s CNV, and Yuri Popov, an internationally respected plant biologist from Yerevan State University.