Envelope gene of the human endogenous retrovirus HERV-W encodes a functional retrovirus envelope

Abstract

A member of the human endogenous retrovirus (HERV) family termed HERV-W encodes a highly fusogenic membrane glycoprotein that appears to be expressed specifically in the placenta. It is unclear whether the glycoproteins of the HERVs can serve as functional retrovirus envelope proteins to confer infectivity on retrovirus particles. We found that the HERV-W envelope glycoprotein can form pseudotypes with human immunodeficiency virus type 1 virions and confers tropism for CD4-negative cells. Thus, the HERV-W env gene represents the first HERV env gene demonstrated to encode the functional properties of a retrovirus envelope glycoprotein.

FIG. 1

HIV-1 can be pseudotyped with the HERV-W envelope. 293T cells were cotransfected with an HERV-W envelope expression construct and an HIV-1 vector (NLEGFPΔBgIVprX) or a MLV vector construct (SRαEGFP) (1) and packaging plasmid (SVϕ⁻env⁻MLV) (6). 293T cells (5 × 10⁴) were infected with 1 ml of the supernatant from the cotransfected 293T cells in the presence (+RTI) or absence (−RTI) of zidovudine (5 μM) and nevirapine (5 μM). The concentration of p24 in the HERV-W envelope- and HIV vector-cotransfected supernatant was 1,159 ng/ml. Two days postinfection, cells were analyzed for EGFP expression by flow cytometry. Mock-transfected cells (no infection) were analyzed in parallel. The x axis represents the logarithmic fluorescence intensity of EGFP; the y axis represents the number of events. The percentage of EGFP-positive populations was as indicated in each panel. Ten thousand events were acquired for flow cytometric analysis. The data shown here are representative of three independent experiments.