The influence of semen-derived enhancer of virus infection on the efficiency of retroviral gene transfer.

BACKGROUND

An improvement of retroviral infection has been postulated using a naturally occurring fragment of the abundant semen marker prostatic acidic phosphatase. This peptide, termed semen-derived enhancer of virus infection (SEVI), promotes HIV attachment to the target cells.

METHODS

In the present study, we examined whether SEVI would also enhance the infectivity of other viruses with different envelope proteins. We focused on retroviruses pseudotyped with envelopes that are commonly used for the genetic modification of cells, in particular, T cells and hematopoietic progenitor cells. Because the effect of SEVI is considered to be a result of its cationic properties, we compared SEVI with other cationic agents such as protamine sulfate and Polybrene.

RESULTS

We found that SEVI increases the efficiency of gene transfer for lentiviral and gammaretroviral vector constructs pseudotyped with VSV-G, GALV, RD114 or foamy viral envelopes on hematopoietic and nonhematopoietic cell lines. On T cells, the transduction efficiency of GALV and RD114 pseudotyped vectors was significantly increased by SEVI. A significant increase of the gene transfer rate was also detected for foamy virally pseudotyped lentivirus on murine hematopoietic progenitor cells. No toxic effect of SEVI treatment was detected on any cell type tested, including human and murine hematopoietic stem/progenitor cells. When directly comparing the effect of SEVI with Polybrene or protamine sulfate, we show that the semen-derived protein is more efficient in increasing the gene transfer rate.

CONCLUSIONS

SEVI is a promising agent for promoting and improving gene transfer and may also be useful for clinical gene therapy studies.